Science AI Journal
Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Amyloidosis: Diagnosis, Treatment, Outcomes

26 unresolved questions extracted from the limitations and future-work sections of 229 Amyloidosis: Diagnosis, Treatment, Outcomes papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Abstract Aims Tafamidis was the first drug approved for transthyretin amyloid cardiomyopathy (ATTR-CM), but contemporary real-world evidence is lacking.

    Contemporary Real-World Treatment of Cardiac Transthyretin Amyloidosis with Tafamidis: A Long-Term Multicentre Study · 2026 · DOI

  • Although a few reports have described dyspnea (14), hoarse- ness or chronic cough has rarely been documented—which may reflect a genuinely low incidence, or alternatively, may be due to the fact that previous studies did not systematically observe such symptoms.

    Case Report: When peripheral neuropathy meets hoarseness and cough: a diagnostic challenge and insights from a case of late-onset ATTRv · 2026 · DOI

  • Background Radionuclide SPECT/computed tomography (CT) is standard for diagnosing transthyretin cardiac amyloidosis (ATTR-CM), but the prognostic value of quantitative metrics remains incompletely defined.

    Quantitative single photon emission computed tomography/computed tomography of Tc-99m-pyrophosphate scans: metrics for short-term risk stratification in transthyretin cardiac amyloidosis · 2026 · DOI

  • Despite significant progress in the diagnosis and treatment of ATTR-CM, several fundamental issues remain unresolved: - combination therapy: will the simultaneous use of a stabilizer and a gene-silencing drug yield a synergistic effect? Even if studies demonstrate the benefit of combination therapy, its cost may be prohibitively high. - amyloid regression: a new approach to treating ATTR-CM involves monoclonal antibodies targeted directly at existing deposits in the heart. This could be a breakthrough for patients in advanced stages of the disease, for whom tetramer stabilization alone is insufficient [25]. - early diagnostics: the use of artificial intelligence (AI) in ECG and echocardiography analysis may allow for the identification of ATTR-CM patients at the preclinical stage, before irreversible myocardial damage occurs [14].

    Transthyretin cardiomyopathy – diagnosis and therapeutic options · 2026 · DOI

  • Although envi- ronmental and lifestyle-related factors, including sunlight exposure and oxidative stress, have been proposed in rela- tion to wild-type ATTR-CM,7 current evidence remains insufficient to account for the magnitude and consistency of the nationwide disparities.

    Geographical Disparities in the Detection and Certification of Systemic Amyloidosis in Japan ― A Nationwide Registry Analysis, 2015–2024 ― · 2026 · DOI

  • Because several family members were diagnosed at advanced stages, the precise symptom-onset age could not be determined in all individuals; however, the pedigree consistently suggested earlier and more aggressive disease expression in men and clinically meaningful intrafamilial variation (Table 1, Figure 3).

    Revisiting Predicted Age of Disease Onset in a Korean Kindred with the Transthyretin Asp38Val Variant · 2026 · DOI

  • Finally, although limited by a small sample size (n = 4), our study included patients treated with Importantly, even patients with severe organ dysfunction may maintain a level of daily functioning comparable to e v i l A ) 8 2 6 ( ) 6 3 0 , 1 ( e v i l A h t a e d e s a e s i D ) 3 0 1 ( that before disease onset when managed with individualized treatment plans that carefully balance the disease burden with drug toxicity.

    Daratumumab-based therapy in systemic AL amyloidosis including advanced cardiac involvement: a single center study · 2026 · DOI

  • Limitations of this study are noted. Factors not explored in this study, such as treatment availability, ease of access, cost, and reimbursement pathways, are also likely drivers of patients’ treatment decisions. Although the results may not be generalizable to the broader ATTR‑CM population, the confirmatory survey showed that ATTR‑CM treatment preferences and priori‑ ties were generally consistent in a larger sample.

    Patient Perspectives on Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Treatment Attributes · 2026 · DOI

  • Third, we lacked data on troponin levels from laboratory tests and global longitudinal strain calculated using echocardiography. Fourth, in this study, we could not assess whether the HBR is superior to SPECT/CT interpretation for diagnosis of ATTR-CM.

    Diagnostic and prognostic value of 99mTc-pyrophosphate SPECT/CT in patients with transthyretin amyloid cardiomyopathy · 2026 · DOI

  • A limitation of our case report is the absence of endomyocardial biopsy and cardiac MRI, the latter not performed due to the patient’s deranged renal function tests (serum creatinine 2.3 mg/dL). Despite this, comprehensive echocardiographic evaluation revealing the characteristic ‘‘cherry-on-top’’ GLS pattern (−9.7% initially, deteriorating to −1.9%) combined with supportive clinical findings (refractory heart failure, LVH in a normotensive patient) and renal biopsy confirmation of AL amyloidosis provided sufficient diagnostic certainty for cardiac involvement. This non invasive multimodal approach aligns with studies demonstrating that such assessments often negate the need for invasive endomyocardial biopsy in systemic AL amyloidosis with strong imaging evidence, as shown by Aljama et al. where NT-proBNP plus echocardiography diagnosed cardiac involvement in most patients without requiring biopsy18. What we have learned? Clinicians should maintain a high index of suspicion for cardiac amyloidosis in patients with multiple myeloma presenting with heart failure and unexplained left ventricular hypertrophy. Global longitudinal strain should be routinely incorporated into echocardiographic assessment in this population, as the characteristic apical sparing pattern provides an important noninvasive diagnostic clue. Serial GLS evaluation is a practical tool for monitoring disease progression and prognostication. Early identification of cardiac involvement and close collaboration between cardiology and hematology teams are essential to guide management and improve outcomes. REFERENCES [1] Falk RH, Alexander KM, Liao R, Al DS. Light-chain cardiac amyloidosis: A review of diagnosis and therapy. J Am Coll Cardiol. 2016;68(12):1323–1341. [2] Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989–995. doi: 10.1200/JCO.2011.38.5724. [3] Merlini G, Dispenzieri A, Sanchorawala V, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4(1):38. doi: 10.1038/s41572-018-0034-3. [4] Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, Klarich KW, Miller WL, Maleszewski JJ, Dispenzieri A. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68(10):1014–1020. [5] Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types: Disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203–1212. doi: 10.1161/CIRCULATIONAHA.108.843334. [6] Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two- dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart . 2012;98(19):1442–1448. doi: 10.

    Cardiac amyloidosis presenting as refractory heart failure: Role of GLS in diagnosis and on follow up · 2026 · DOI

  • , DepleTTR-CM with ALXN2220) and other compounds, such as doxycycline or epigallocatechin-3-gallate (a green tea component), which, despite long-standing recognition, remain underexplored.

    Advancing treatments for transthyretin amyloid cardiomyopathy: Innovations in RNA silencing, gene editing, TTR stabilization, and degradation · 2025 · DOI

  • ATTR is generally considered a mainly neurological disease, but it is phenotypically heterogeneous and the clinical spectrum of the disease varies widely, which makes the diagnosis a real challenge.

    Nowe metody diagnostyki amyloidozy serca. Seria przypadków amyloidozy transtyretynowej · 2018 · DOI

  • If it be accepted that 12 patients are suffering from a neurological syndrome determined by uncontrolled diabetes, the total clinical picture would seem to be different from that visualized in is still true to say that the most usual features are diffuse pain, weakness, wasting, and areflexia, usually asymmetrical and limited to the legs.

    Diabetic Amyotrophy · 1955 · DOI

  • Nevertheless, given the challenging accessibility of the analyzed samples, the proposed landscape of results provides a valuable resource to encourage further studies on cardiac amyloidosis.

    A journey through the molecular networks of endomyocardial biopsies to explore ATTR and AL<i>λ</i> cardiac amyloidosis. · 2026 · DOI

  • Together, these findings show that amyloidosis is preceded by persistent plasma proteomic alterations, providing a framework for early risk stratification and insight into the preclinical biology of this under-recognised disease.

    Early plasma proteomic alterations precede amyloidosis diagnosis, reflecting cardiac and immune dysregulation · 2026 · DOI

  • 2 While this type of localized amyloidosis is believed to be caused by excessive accumulation of amyloid in specific tissues or organs, the precise mechanism remains unknown.

    A Case of Localized Gastric Amyloidosis With Improvement on Endoscopy After Eradication of Helicobacter pylori · 2026 · DOI

  • Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.

    Glomerulopathies with Fibrillary Deposits · 2023 · DOI

  • Because of the rareness, differential clinical manifestations and limited knowledge concerning the pathogenesis of amyloidoses of particular types, multiple medical terms developed in the professional literature to describe the same disease entity.

    Zasady klasyfikacji i nazewnictwa amyloidoz · 2018 · DOI

  • Monoclonal protein most often can be detected as an extra band on serum protein pattern, nevertheless if it is lacking pathological condition cannot be excluded.

    Role of laboratory tests in diagnosis of multiple myeloma and other plasmocytes dyscrasia patients · 2015 · DOI

Most-cited papers in Amyloidosis: Diagnosis, Treatment, Outcomes

Most recent work

Find a gap in your own Amyloidosis: Diagnosis, Treatment, Outcomes sub-topic

This page shows what the Amyloidosis: Diagnosis, Treatment, Outcomes literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Biochemistry, Genetics and Molecular Biology

Gut microbiota and health
289 open questions
Single-cell and spatial transcriptomics
185 open questions
dental development and anomalies
121 open questions
Mitochondrial Function and Pathology
110 open questions
Genetic Associations and Epidemiology
106 open questions
Human-Animal Interaction Studies
105 open questions
Genomics and Chromatin Dynamics
97 open questions
Inflammatory Bowel Disease
91 open questions
26 open questions have been extracted from the limitations and future-work passages of 229 Amyloidosis: Diagnosis, Treatment, Outcomes papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.