Highlights
- Early diagnosis of cardiac amyloidosis significantly improves prognosis and treatment outcomes.
- Emerging therapies promise better management, emphasizing the importance of multidisciplinary care and support.
Summary and Overview
Cardiac amyloidosis is a progressive condition caused by misfolded amyloid protein deposits in the heart, leading to thickened cardiac walls, impaired function, arrhythmias, and heart failure. The main types are immunoglobulin light chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, which includes hereditary and wild-type forms. Symptoms vary widely, from exertional dyspnea and fatigue to extracardiac signs like carpal tunnel syndrome and peripheral neuropathy. AL amyloidosis may cause periorbital purpura, while ATTR can involve vision changes and tendon ruptures. Diagnosis combines clinical suspicion, imaging (echocardiography, cardiac MRI), laboratory tests, and sometimes biopsy. Early diagnosis is critical due to poor prognosis, with median survival 2–4 years after diagnosis. Treatment differs by subtype, including chemotherapy and monoclonal antibodies for AL, and transthyretin stabilizers or gene silencers for ATTR, alongside supportive care for heart failure and arrhythmias.
Clinical Presentation and Diagnosis
Cardiac amyloidosis presents with diverse cardiac and systemic symptoms, often causing delayed diagnosis. Heart failure symptoms include dyspnea, fatigue, and peripheral edema, with diastolic dysfunction common. ECG changes like low voltage and conduction blocks are typical. Systemic features include peripheral and autonomic neuropathies, carpal tunnel syndrome, lumbar stenosis, tendon rupture, and gastrointestinal symptoms. Specific signs like periorbital purpura suggest AL amyloidosis. Echocardiography reveals thickened myocardium and characteristic strain patterns; cardiac MRI shows late gadolinium enhancement but cannot differentiate subtypes. Diagnosis relies on serum and urine tests for monoclonal proteins to identify AL amyloidosis; if absent, bone scintigraphy confirms ATTR amyloidosis non-invasively. Tissue biopsy remains the definitive test when diagnosis is uncertain.
Treatment
Treatment targets the underlying amyloid type. AL amyloidosis therapy focuses on reducing light chain production using chemotherapy, stem cell transplant in eligible patients, and emerging monoclonal antibodies like daratumumab. Hematologic response correlates with improved survival. ATTR amyloidosis is treated with transthyretin stabilizers such as tafamidis and gene-silencing therapies that reduce transthyretin production. Supportive care includes careful use of diuretics, management of arrhythmias with rate/rhythm control and anticoagulation, and cautious use of implantable devices. Advanced cases may be considered for heart or combined liver-heart transplantation, though eligibility is limited. Palliative care is essential for symptom control and quality of life, especially in advanced disease. Ongoing trials are evaluating novel agents to improve outcomes.
Prognosis and Patient Management
Cardiac amyloidosis generally has a poor prognosis, with median survival of 2–4 years post-diagnosis. Delays in diagnosis—often exceeding 20 months—worsen outcomes and are influenced by symptom variability, lack of awareness, and social determinants such as socioeconomic status and race. Frailty is an independent predictor of survival. Effective management requires a multidisciplinary approach with regular monitoring of clinical status, hematologic and organ responses, and imaging assessments. Patient education on symptom recognition and adherence to therapy is vital. Nutritional support is important due to frequent undernutrition. Imaging techniques like echocardiography, bone scintigraphy, and cardiac MRI guide diagnosis and treatment monitoring.
Psychosocial Aspects and Research
Cardiac amyloidosis significantly impacts quality of life, causing physical limitations, emotional distress, and cognitive challenges. Individualized care plans and practical aids improve treatment adherence. Social factors affect disease severity and access to care, emphasizing the need for equitable healthcare. Referral to specialized centers can improve diagnostic accuracy, provide access to clinical trials, and offer multidisciplinary support. Recent research has advanced subtype-specific therapies and noninvasive diagnostics, reducing reliance on biopsy. Emerging treatments, including monoclonal antibodies to clear amyloid deposits, are under clinical evaluation. Future directions include leveraging artificial intelligence to enhance early diagnosis and personalized management.
The content is provided by Sierra Knightley, Scopewires
