Panelists discuss how diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM) and transthyretin amyloid polyneuropathy (ATTR-PN) involves recognizing key differences in organ involvement, with ATTR-CM primarily affecting the heart and ATTR-PN impacting the nervous system, and emphasize the importance of tailored diagnostic approaches using genetic testing, imaging, and biopsies for accurate identification and treatment.
Primary organ involvement: ATTR-CM primarily affects the heart, leading to restrictive cardiomyopathy with symptoms of heart failure, arrhythmias, and sometimes conduction abnormalities.
Diagnostic approach:
Clinical presentation: Patients typically present with heart failure symptoms, arrhythmias (including atrial fibrillation), and brady/tachy arrhythmias.
Cardiac biomarkers: Elevated NT-proBNP and cardiac troponins
Imaging: Echocardiography and cardiac MRI can show thickened heart walls, restrictive filling patterns, and amyloid deposits.
Genetic testing: Identifying mutations in the TTR gene can confirm hereditary forms of ATTR-CM.
Tissue biopsy/scintigraphy: Confirmation can be done through tissue biopsy showing amyloid deposits or using bone scintigraphy (with technetium-labeled agents).
Primary organ involvement: ATTR-PN predominantly affects the nervous system, leading to peripheral neuropathy, autonomic dysfunction, and sometimes carpal tunnel syndrome (CTS).
Diagnostic approach:
Clinical presentation: Patients often present with sensory and motor neuropathy, pain, numbness, and weakness, typically in the distal limbs. They may also have autonomic symptoms, such as orthostatic hypotension or gastrointestinal dysfunction.
Nerve conduction studies: Can detect slowed nerve conduction and reduced amplitude, confirming neuropathy
Electromyography: Used to assess the extent of motor involvement in the peripheral nerves
Genetic testing: Like ATTR-CM, genetic testing for TTR mutations is essential for confirming the hereditary form of ATTR-PN.
Tissue biopsy: Similar to ATTR-CM, a biopsy may be performed to confirm amyloid deposits in the peripheral nerves.
Key Differences in Diagnosis:
Organ system affected: ATTR-CM primarily affects the heart, whereas ATTR-PN affects the peripheral nervous system. However, both can share extracardiac manifestations such as CTS.
Symptoms: ATTR-CM presents mainly with cardiac symptoms (heart failure, arrhythmias), whereas ATTR-PN presents with neurological symptoms (numbness, pain, weakness).
Diagnostic testing: Although both conditions can be confirmed via genetic testing for TTR mutations, scintigraphy and tissue biopsy help identify amyloid deposits in the heart for ATTR-CM and in the nerves for ATTR-PN.
Understanding these differences is crucial for accurate diagnosis and ensuring proper treatment tailored to each condition.