Hereditary

UNDERSTANDING HEREDITARY
ATTR-CM (hATTR-CM)

WHAT IS hATTR-CM?

hATTR-CM is a type of amyloidosis caused by a mutation in the TTR gene.1hATTR-CM is inherited in an autosomal dominant pattern, meaning only 1 affected parent is required to pass on the mutation.2 Though a mutation in the TTR gene is associated with an increased risk for hATTR-CM, not all people who carry this mutation will go on to develop the disease.1

hATTR-CM is primarily associated with infiltrative cardiomyopathy, though the clinical spectrum of hereditary ATTR (hATTR) amyloidosis varies widely and can include progressive sensorimotor and autonomic neuropathy.3-5

~75%About 75% of patients with hATTR amyloidosis exhibited cardiomyopathic features of the disease.3

>30%Carpal tunnel syndrome is also common and can often be the initial symptom in more than 30% of hATTR-CM patients, with cardiomyopathy symptoms following as the disease progresses.6

AN OVERVIEW OF hATTR-CM

RECOGNITION OF CARDIAC INVOLVEMENT IN HEREDITARY AMYLOIDOSIS (VIA NT-proBNP MEASUREMENTS) IS CRITICAL, AS CARDIAC INVOLVEMENT IS ASSOCIATED WITH ADVERSE OUTCOMES AND WORSE OVERALL SURVIVAL, REGARDLESS OF PHENOTYPE.10

NT-proBNP, N-terminal pro-B-type natriuretic peptide.

PATIENT CONSIDERATIONS

  • African American, African, or Afro-Caribbean descent (V122I)5,7,8
  • Irish descent (T60A)8
  • Men and women5
  • Symptom onset may occur as early as 50-60 years of age9*

PROGNOSIS

Once diagnosed, untreated patients have a median survival of ~2 to 3 years.8

COMMON CHARACTERISTICS THAT MAY PRESENT IN hATTR-CM PATIENTS:

  • Heart failure5
  • Peripheral dysfunction (eg, peripheral sensorimotor dysfunction, peripheral neuropathy)5
  • Autonomic dysfunction (eg, autonomic neuropathy, gastrointestinal complaints, unexplained weight loss, orthostatic hypotension, sexual impotence)5,9
  • History of bilateral carpal tunnel syndrome5

*Age of onset varies depending on the causative mutation.

Selected genotype-phenotype
associations in hATTR amyloidosis*

In hATTR amyloidosis, the clinical manifestation depends on mutation type, geographic origin of the patient, patient ethnicity, and other factors.11

Select each individual mutation type

for more information on clinical manifestations, age of onset, and patient heritage.

V30M Early Onset
Clinical
Manifestations
Predominant neurological manifestations10
Approximate
Age of Onset
30-4011
Typical
Patient Heritage
Portuguese10
Japanese 10
V30M Late Onset
Clinical
Manifestations
Cardiac and neurological manifestations12
Approximate
Age of Onset
50-609
Typical
Patient Heritage
Swedish13
T60A
Clinical
Manifestations
Cardiac and neurological manifestations13
Approximate
Age of Onset
50-609
Typical
Patient Heritage
Irish8
English13
L111M
Clinical
Manifestations
Predominant cardiac manifestations14
Approximate
Age of Onset
30-409
Typical
Patient Heritage
Danish9
I68L
Clinical
Manifestations
Predominant cardiac manifestations14
Approximate
Age of Onset
5515
Typical
Patient Heritage
Italian8
V122I
Clinical
Manifestations
Predominant cardiac manifestations13
Approximate
Age of Onset
50-609
Typical
Patient Heritage
African American13
African8
Afro-Caribbean8
"Neurologic"
PHENOTYPE
"Cardiac"

About 75% of patients with hATTR amyloidosis exhibited cardiomyopathic features of the disease.3

*This spectrum of genotype-phenotype associations is not comprehensive.

DIAGNOSTIC URGENCY

In patients with hATTR-CM, survival depends on the mutation and can range from 2 to 5 years from initial presentation in untreated patients.16-18

ADVANCED hATTR-CM IN UNTREATED PATIENTS IS ASSOCIATED WITH RAPID PROGRESSION, SERIOUS CARDIAC COMPLICATIONS, AND A WORSE MEDIAN SURVIVAL.5,8,19 THEREFORE, EARLY DETECTION IS CRITICAL, AS SURVIVAL WORSENS AS hATTR-CM ADVANCES.19

COULD HEART FAILURE IN YOUR AFRICAN AMERICAN PATIENTS BE A CAUSE OF hATTR-CM?

In the United States, the most common mutation causing the cardiac form of the disease (hATTR-CM) is the V122I mutation. This mutation affects almost exclusively the African American population.5,7,8

hATTR-CM due to the V122I mutation is an underdiagnosed cause of heart failure in individuals of African ancestry.20

THAOS, Transthyretin Amyloid Outcome Survey.

V122I PRIMARILY PRESENTS WITH CARDIAC MANIFESTATIONS

In 1 study, the most common clinical presentation with hATTR-CM due to the V122I mutation was heart failure. The second most frequent symptom was carpal tunnel syndrome.21

hATTR-CM IS OFTEN UNDERRECOGNIZED, AND INDIVIDUALS OF AFRICAN DESCENT WITH hATTR-CM DUE TO V122I CAN BE ESPECIALLY OVERLOOKED.20,22 IT IS IMPORTANT TO DISTINGUISH THESE PATIENTS FROM THOSE WITH OTHER FORMS OF CARDIOMYOPATHY AND HEART FAILURE.22

V122I PATIENT PROFILE

A CLINICAL PROFILE FOR A 67-YEAR-OLD MAN DISPLAYING THE CLINICAL SIGNS OF hATTR-CM

*Hypothetical profile. Not an actual patient.

99mTc-PYP is not FDA approved for the diagnosis of ATTR-CM. Please consult individual labeling for risks.

99mTc-PYP, 99mtechnetium-labeled pyrophosphate.

JOE’S MEDICAL AND FAMILY HISTORY SHOULD RAISE SUSPICION OF hATTR-CM—A PROGRESSIVE, LIFE-THREATENING DISEASE22

Meet Joe*—A 67-Year-Old Retired High School Teacher

Family history

  • Mother died due to complications from heart failure at age 63
  • Brother suffered a stroke

Presentation and medical history

  • Currently experiencing shortness of breath and fatigue
  • History of hypertension, although blood pressure is controlled with appropriate medication
  • Echocardiographic evidence of increased left ventricular wall thickness
  • History of carpal tunnel syndrome with bilateral surgical repair

Diagnosis

  • AL amyloidosis was ruled out
  • Cardiac imaging using 99mTc-PYP was consistent with ATTR-CM
  • Genetic testing identified the V122I mutation of the TTR gene, consistent with the hereditary form of ATTR-CM

UNDERSTANDING GENETIC RISK

DIAGNOSIS OF hATTR-CM IN AN INDEX PATIENT SHOULD PROMPT GENETIC COUNSELING AND TESTING OF FAMILY MEMBERS15

  • Early identification of hATTR-CM is important to enable timely treatment15
  • Genetic counseling and testing can be especially beneficial in at-risk family members, such as siblings or children of an index patient15

TIMING OF GENETIC TESTING15

  • A targeted approach may enable diagnosis of disease upon the first detectable sign or symptom
genetics testing
genetics testing

*Percentage of individuals with a mutation who exhibit clinical symptoms.

LIFE-THREATENING, UNDERRECOGNIZED, AND UNDERDIAGNOSED, IT IS VITAL TO RECOGNIZE THE CLUE OF CLUES OF hATTR-CM SO YOU CAN IDENTIFY THIS DISEASE.8,23,24

GET SUSPECT AND DETECT ATTR-CM UPDATES

Sign up to be alerted about new educational resources
to help you suspect and detect ATTR-CM.

Sign Up