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Understanding Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Amyloidosis is a group of diseases in which amyloid fibrils deposit into the extracellular spaces of different organs, which ultimately leads to progressive organ dysfunction.1,2 The amyloid fibrils are formed by an aggregation of misfolded proteins. The most common amyloid fibril proteins that can infiltrate the heart and lead to cardiac amyloidosis1 are immunoglobulin light chain amyloid fibril protein (AL) and transthyretin amyloid fibril protein (ATTR).2-5

Most Common Types of Cardiac Amyloidosis

ATTR amyloidosis5

AL amyloidosis5

Wild-type ATTR (wtATTR)5

Hereditary ATTR (hATTR)1

Also known as variant1

Learn more

It is important to clinically differentiate between ATTR and AL, as they have different clinical courses,5
and AL requires immediate treatment.6

Wild-type vs HEREDITARY ATTR-CM

Wild-type ATTR-CM (wtATTR-CM) is idiopathic7 and is not considered to be a hereditary disease.1 It is thought to account for the majority of all ATTR-CM cases.8

Hereditary ATTR (hATTR)* occurs due to a mutation in the TTR gene (learn more). In the United States, the most common mutation causing the cardiac form of the disease (hATTR-CM) is the valine-to-isoleucine substitution at position 122 (V122I).8 This mutation affects almost exclusively the African American population, with a prevalence of about 3%-4%.3,9 The second most common mutation is T60A, which occurs predominantly in people of Irish descent.3 Not all patients who carry a TTR mutation will go on to have clinical signs and symptoms of this disease.

 

*Also known as variant ATTR.1

 

Wild-type ATTR-CM (wtATTR-CM)

Also known as7,8

  • Senile cardiac amyloidosis
  • Senile systemic amyloidosis
  • Age-related amyloidosis

Patient considerations

Men
  • Ethnicity: predominantly white7,8
  • Mostly men7,8,10
  • Symptom onset typically over the age of 60 years11
  • Heart failure7,8,10
  • Cardiac arrhythmias,
    particularly atrial fibrillation3,7,8,10
  • History of bilateral carpal tunnel syndrome7,10,12

Prognosis

  • Median survival: ~3.5 years7,10,13

Hereditary ATTR-CM (hATTR-CM)

Also known as

  • Variant ATTR (ATTRv) amyloidosis1
  • ATTRm amyloidosis1
  • Mutant ATTR amyloidosis4
  • Hereditary amyloidosis14
  • Familial amyloid cardiomyopathy15

Patient considerations

Men
  • African American, African,
    or Afro-Caribbean descent (V122I)3,8
  • Irish descent (T60A)3
  • Men and women8
  • Symptom onset may occur as early as 50-60 years of age11,16
  • Heart failure8
  • Neurological symptoms
    (peripheral and autonomic)8
  • Gastrointestinal symptoms8
  • History of bilateral carpal tunnel syndrome8

Prognosis

  • Median survival: ~2 to 3 years3

wtATTR IS THOUGHT TO ACCOUNT FOR THE MAJORITY OF ATTR-CM CASES8

Encountering ATTR-CM

Meet Dr. Detective, a cardiologist who specializes in diagnosing tough cases. Watch as he suspects and then detects that his patient has ATTR-CM.

 

Clinical presentation of ATTR-CM
IN PATIENTS WITH wtATTR AND hATTR*

Patients with wtATTR-CM and hATTR-CM present with heart failure and other cardiac symptoms.4,7,8,10,17-20
Please see other common signs and symptoms in the image below.

Common signs and symptoms in
wtATTR‑CM AND hATTR‑CM4,7,8,10,17-20*

Attr bodies
Attrwt hattr

CTS, carpal tunnel syndrome; GI, gastrointestinal; HFpEF, heart failure with
preserved ejection fraction.

*Also known as variant ATTR.1

Cardiac

  • Fatigue
  • Shortness of breath
  • Edema
  • Arrhythmias
  • HFpEF
  • Aortic stenosis

Soft Tissue

  • Lumbar spinal stenosis
  • Biceps tendon rupture

GI

  • Diarrhea
  • Constipation
  • Nausea
  • Early satiety
  • Unintended weight loss

Neurologic

  • Carpal tunnel syndrome
  • Peripheral neuropathy
  • Orthostasis
  • Weakness

ATTR-CM is an underdiagnosed cause of heart failure PARTICULARLY HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFpEF)21,22

In 2 studies, wtATTR deposits were identified in the hearts of 13%-17% of older patients with HFpEF.21,22

  • In an ex-US study of 120 HFpEF patients 60 years or older, wtATTR was confirmed in 13% (13.3%; 95% CI: 7.2-19.5) of the patients21
  • In a US study of 140 autopsied patients, 109 of whom had HFpEF, cardiac wtATTR deposits were found in 17% of the patients22

Know the clues to look for to avoid missing a diagnosis. Learn the clues

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