From the Guidelines
ATTR-CM is a progressive heart disease caused by the buildup of abnormal transthyretin protein (amyloid) in the heart muscle, leading to heart failure symptoms and decreased quality of life, with a poor life expectancy of 2-6 years after diagnosis 1. This condition occurs in two forms: hereditary (caused by genetic mutations) and wild-type (age-related, not inherited). Key characteristics of ATTR-CM include:
- Abnormal fibrils derived from transthyretin (TTR) that aggregate and deposit in tissues and organs
- Common manifestation of ATTR amyloidosis
- Associated with debilitating physical symptoms common to heart failure (HF), such as exercise intolerance and fatigue
- Results in decreased functional capacity, diminished quality of life, and eventual death Diagnosis and treatment of ATTR-CM are crucial to improve quality of life and survival rates, with treatment options including medications that stabilize the transthyretin protein to prevent amyloid formation, as well as management of heart failure symptoms 1. Important aspects of ATTR-CM management include:
- Early diagnosis to start treatment before significant heart damage occurs
- Use of medications such as tafamidis to stabilize the transthyretin protein
- Management of heart failure symptoms with diuretics, blood pressure medications, and sometimes pacemakers
- Consideration of the disease's progression and impact on quality of life and survival rates 1.
From the Research
Definition and Overview of ATTR-CM
- Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment 2.
- It is a systemic disease that can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms) 2.
- ATTR-CM is characterized by the aggregation and deposition of amyloidogenic misfolded transthyretin (TTR) in the myocardium, resulting in restrictive cardiomyopathy and heart failure 3.
Clinical Manifestations and Diagnosis
- ATTR-CM can lead to a number of cardiovascular manifestations, including heart failure, rhythm disturbances, and valvular disease 4.
- Early clinical recognition and prompt diagnosis are crucial to improving disease-related outcomes, and advances in diagnostic modalities have improved the detection of ATTR-CM 4.
- The availability of new disease-modifying therapies has made successful treatment a reality, and treatment benefits are largely consistent between patients with wild-type TTR and patients with a variant TTR genotype 3.
Treatment Options
- Tafamidis, a TTR stabilizer, has been approved for use in the treatment of adults with ATTR-CM in several countries, and has been shown to reduce all-cause mortality and frequency of cardiovascular-related hospitalizations 3, 5.
- Tafamidis stabilizes both wild-type and mutant TTR, inhibiting the formation of TTR amyloid fibrils, and has been demonstrated to slow disease progression and improve outcomes in patients with ATTR-CM 3, 5.
- The optimal dose of tafamidis is 80 mg, which has been shown to reduce mortality and cardiovascular-related hospitalizations in patients with ATTR-CM, with a significantly greater survival benefit compared to the 20 mg dose 6.
Importance of Early Diagnosis and Treatment
- Early diagnosis and treatment are critical to improving outcomes in patients with ATTR-CM, as treatment benefits are largely consistent between patients with wild-type TTR and patients with a variant TTR genotype 2, 3.
- Increasing disease awareness is crucial to achieving an early and accurate diagnosis, and patients seek to receive care at specialized amyloidosis centers and be fully informed about their treatment and prognosis 2.