Clinical Manifestation of ATTR-CM and Red Flag Symptoms

Summary for Physicians: Clinical Manifestations and Red Flag Symptoms of ATTR-CM

Clinical Manifestations of ATTR-CM:

1. Cardiac symptoms:
   1. Heart failure (HF), often with restrictive cardiomyopathy
   2. Atrial arrhythmias that are resistant to ablation procedures
   3. Bradyarrhythmias and tachyarrhythmias
   4. Pacemaker dependence in advanced cases
2. Extracardiac symptoms:
   1. Bilateral carpal tunnel syndrome (CTS): Often a key early sign of the disease
   2. Spinal stenosis: May cause discomfort or neurological deficits
   3. Trigger fingers: Common in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR-CM)
3. Pulmonary embolism: Can occur in advanced stages
4. Electrocardiogram findings:
   1. May show signs of low-voltage QRS complexes, heart block, or other arrhythmias typical of restrictive cardiomyopathy
5. Imaging:
   1. Echocardiography and cardiac MRI often show characteristic features of restrictive cardiomyopathy or amyloid deposits.
   2. Chest x-ray may show evidence of HF.
6. Laboratory findings:
   1. Elevated biomarkers such as NT-proBNP and troponins can be seen in cardiac involvement.
   2. Genetic testing can confirm the diagnosis of hATTR-CM.

Red Flag Symptoms for hATTR-CM:

• Persistent bilateral CTS, spinal stenosis, and trigger fingers should raise suspicion of hATTR-CM, especially in patients with unexplained HF or arrhythmias.
• A history of family members with similar symptoms or genetic mutations associated with ATTR-CM further supports the diagnosis.

Early recognition of these symptoms is essential for timely diagnosis and intervention in patients with ATTR-CM.