The diagnostic challenges of cardiac amyloidosis: A practical approach to the two main types
Cindy Varga1, Sharmila Dorbala2, Isabelle Lousada3
1Department of Medicine, The John C Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA, USA.
Insights
Systemic amyloidosis, including immunoglobulin light-chain (AL) and transthyretin (ATTR) types, requires rapid diagnosis and effective treatment. Advances in diagnostic tools and therapies are improving patient outcomes for these multisystem protein deposition diseases.
Area of Science:
- Cardiology
- Hematology
- Neurology
- Nephrology
Background:
- Systemic amyloidosis, encompassing immunoglobulin light-chain (AL) and transthyretin (ATTR) types, is a multisystem protein deposition disease frequently affecting the heart.
- Diagnostic delays in systemic amyloidosis significantly worsen patient outcomes.
- Recent advancements allow for rapid differentiation and effective treatment of both AL and ATTR amyloidosis.
Purpose of the Study:
- To present the current landscape of diagnosing and treating AL and ATTR amyloidosis.
- To emphasize the coordinated clinical application of new diagnostic tools and therapeutic agents.
- To guide the rapid identification of amyloid type and rational selection of therapy for improved patient management.
Main Methods:
- Review of recent advances in radioisotope scintigraphy, monoclonal protein testing, and mass spectrometry for amyloid typing.
- Evaluation of novel therapeutic agents for AL amyloidosis, including proteasome inhibitors, immunomodulators, and monoclonal antibodies.
- Assessment of emerging treatments for ATTR amyloidosis, such as the stabilizer tafamidis and RNA-interference agents patisiran and inotersen.
Main Results:
- Prognosis for AL amyloidosis has improved with novel agents, though tolerability can necessitate dose adjustments; long-term survival is achievable with complete response.
- Prognosis for both wild-type (ATTRwt) and hereditary (ATTRv) transthyretin amyloidosis is enhanced by new therapies.
- Successful treatment leading to elimination or suppression of the amyloidogenic protein can result in improvement of cardiac, renal, and peripheral nervous system involvement.
Conclusions:
- Coherent approaches integrating new diagnostic and therapeutic modalities are crucial for managing systemic amyloidosis.
- Rapid diagnosis and timely, targeted therapy are essential for saving lives and improving outcomes in patients with AL and ATTR amyloidosis.
- Implementing evidence-based strategies will enable faster amyloid typing and more effective, individualized treatment selection.
Abstract:
Systemic amyloidosis of the immunoglobulin light-chain (AL) or transthyretin type (ATTR) is a multisystem protein deposition disease that often involves the heart. Delays in diagnosis are very common and can have detrimental consequences on patient outcomes. Because both major types can now be distinguished quickly and treated effectively, clear approaches are required. There have been advances in radioisotope scintigraphy, monoclonal protein testing and mass spectrometry for typing that need coordinated application. We have entered an era in which rapid diagnosis and ready therapy will save lives, therefore we must develop coherent approaches to this multisystem disease. The prognosis for AL has improved significantly with the incorporation of novel agents such as proteasome inhibitors, immunomodulators and monoclonal antibodies against plasma cells. Multiple independent studies have demonstrated the efficacy of these agents in AL, though tolerability can become an issue with dose reductions required in many cases. Median overall survival for patients achieving complete responses after stem cell transplant and consolidation exceeds a decade. The prognosis for ATTR, both age-related wild-type (ATTRwt) and hereditary due to variants of transthyretin (ATTRv), has improved as well due to the availability of the stabilizer tafamidis and the RNA-interference agents patisiran and inotersen. In both AL and ATTR, with elimination or suppression of the pathologic amyloid-forming protein, symptomatic involvement of the heart, kidneys and peripheral nervous system can improve as well. In this review, we present the current state of diagnosing and treating the two major types of systemic amyloidosis, emphasizing the coherent clinical application of the new tools and treatments. Implementation of the approaches we provide will enable rapid identification of amyloid type and rational selection of therapy.
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