Submit to Special Issue Submit Abstract to Special Issue Review for JCM Propose a Special Issue

Journal Menu

Journal Browser

Advances in Diagnosis and Treatment of Amyloidosis

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: 25 June 2025 | Viewed by 11077

Share This Special Issue

Special Issue Editor

Dr. Michael Rosenzweig

E-Mail Website
Guest Editor

Department of Hematology & Hematopoietic Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
Interests: Amyloidosis; multiple myeloma; POEMs; Waldenstrom’s macroglobulinemia; monoclonal gammopathy of renal or neurologic significance

Special Issue Information

Dear Colleagues,

In recent years, advances in the diagnosis and treatment of amyloidosis have been abundant and encouraging. The utilization of appropriate techniques to confirm the diagnosis and subtype of amyloid deposition is now increasingly critical as there are effective treatments for both light chain (AL) and transthyretin (TTR) amyloidosis that need to be selected thoughtfully. Immunotherapeutic approaches have led to improved outcomes for patients with newly diagnosed AL amyloidosis, including the first FDA-approved regimen of daratumumab with Cytoxan, bortezomib, and dexamethasone (Dara-CyBorD). Furthermore, immune-based strategies have also contributed to improved outcomes for relapsed disease. The roles of other therapies for AL including high-dose melphalan and autologous stem cell transplantation are evolving. Likewise, for TTR amyloidosis, modern diagnostic modalities and new treatments that either inhibit the production of TTR or stabilize the protein to prevent misfolding are increasingly available. This Special Issue will highlight advances that help shape the approach clinicians take to make an accurate diagnosis of amyloidosis and select the optimal upfront treatment strategy. We also describe advances made for patients with relapsed disease and highlight future modalities under investigation. Finally, the diagnosis and management of specific organ disease including cardiomyopathy, nephropathy, and peripheral/autonomic neuropathy due to amyloidosis will also be discussed.

Dr. Michael Rosenzweig
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

amyloidosis
transthyretin (TTR)
autologous stem cell transplantation (ASCT)
chemotherapy
immunotherapy
cardiomyopathy
nephropathy
neuropathy

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

14 pages, 3830 KiB

Open AccessArticle

Thoracic Fat Pad Biopsy in Cardiac Amyloidosis: Diagnostic Yield in an Afro-Caribbean Population

by Cedrick Mvita Bakatubia, Romain Vergier, Mathilda Simeon, Nathan Buila Bimbi, Nathan Malka, Karima Lounaci, Maria Herrera Bethencourt, Karim Fard, Arnt Kristen, Rishika Banydeen, Astrid Monfort, Jocelyn Inamo and Andreas Müssigbrodt

J. Clin. Med. 2025, 14(5), 1677; https://doi.org/10.3390/jcm14051677 - 1 Mar 2025

Viewed by 549

Abstract

Background/Objectives: Cardiac amyloidosis (CA) is associated with amyloid infiltration of the extra-cardiac tissue, which may occur in the early stages of the disease. This study evaluates the diagnostic utility of thoracic fat pad biopsy obtained during a pacemaker or ICD implantation as an alternative to the standard diagnostic criteria for systemic amyloidosis. Methods: This exploratory, retrospective study included 27 patients with suspected or diagnosed CA who underwent pacemaker or defibrillator therapy. Results: Of these, 16 patients were confirmed to have CA (15 with technetium-labeled bisphosphonate bone scintigraphy and 1 with protein electrophoresis and echocardiographic findings) while 11 were confirmed to be CA-negative. The thoracic fat pad biopsy demonstrated a specificity of 100% but a sensitivity of only 31%. Among patients with transthyretin (ATTR)-CA, the sensitivity remained similarly low, at 27%. These results are consistent with prior findings on abdominal fat pad biopsy in ATTR-CA, highlighting the limited diagnostic yield of this method. Conclusions: Thoracic fat pad biopsy cannot be recommended as a standard diagnostic tool for CA, particularly in ATTR-CA, due to its poor sensitivity. However, in AL (amyloid light-chain) amyloidosis, this minimally invasive procedure may aid diagnosis without additional invasive interventions. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Figure 1

17 pages, 2526 KiB

Open AccessArticle

His108Arg Transthyretin Amyloidosis—Shedding Light on a Distinctively Malignant Variant

by Christina Binder, Lena Marie Schmid, Christina Kronberger, Michael Poledniczek, René Rettl, Johanna Schlein, Nikita Ermolaev, Luciana Camuz Ligios, Michaela Auer-Grumbach, Christian Hengstenberg, Roza Badr Eslam, Johannes Kastner, Jutta Bergler-Klein, Andreas Anselm Kammerlander and Franz Duca

J. Clin. Med. 2024, 13(24), 7857; https://doi.org/10.3390/jcm13247857 - 23 Dec 2024

Viewed by 892

Abstract

Variant transthyretin amyloidosis cardiomyopathy (ATTRv-CM) is a rare form of cardiac amyloidosis associated with many possible mutations in the transthyretin gene, presenting as various distinct clinical phenotypes. Among these, the His108Arg mutation is the most prevalent TTR variant in Austria. However, data describing its clinical phenotype are lacking. This study aims to describe the characteristics, clinical manifestations, and outcomes of patients with the His108Arg variant focusing on cardiac involvement, disease progression, response to therapy, and imaging findings. Methods: Patients were enrolled from a prospective cardiac amyloidosis registry. The baseline assessment included comprehensive echocardiography, cardiac magnetic resonance imaging, a biomarker analysis, and a clinical evaluation. Patients were followed longitudinally, with outcomes such as arrhythmias, heart failure hospitalizations, and response to disease-targeted therapies recorded. Results: Between March 2012 and June 2024, a total of 20 carriers of the His108Arg variant were identified, with 12 exhibiting clear cardiac involvement and 8 remaining asymptomatic. The median age at diagnosis was 62.3 years with significant heterogeneity in the clinical presentation. Patients with ATTRv-CM had a high prevalence of atrial and ventricular arrhythmias, a reduced left ventricular ejection fraction, and elevated cardiac biomarkers. The majority received specific disease-modifying therapies, with varying tolerance and responses. A longitudinal follow-up indicated frequent arrhythmic events, heart failure exacerbations, and three cases of heart transplantation, underscoring the need for stringent monitoring and individualized management strategies. Conclusions: This study represents a unique, comprehensive analysis of the His108Arg variant in ATTR-CM, highlighting its clinical heterogeneity and significant impact on cardiac function and clinical outcomes. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Figure 1

9 pages, 731 KiB

Open AccessArticle

Impact of SGLT2-Inhibitor Therapy on Survival in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis of a Prospective Registry Study

by Nora Schwegel, Christina Toferer, David K. Zach, Viktoria Santner, Viktoria Höller, Jakob Lugitsch, Markus Wallner, Johannes Gollmer, Faisal Aziz, Dirk von Lewinski, Ewald Kolesnik, Klemens Ablasser, Andreas Zirlik, Harald Sourij and Nicolas Verheyen

J. Clin. Med. 2024, 13(19), 5966; https://doi.org/10.3390/jcm13195966 - 8 Oct 2024

Cited by 2 | Viewed by 1802

Abstract

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their safety and effectiveness in patients with ATTR-CM is arising. This study investigates the association between SGLT2i therapy and clinical outcomes in these patients. Methods: This is an analysis of a prospective registry conducted at a referral centre for hypertrophic cardiomyopathies including 116 patients with confirmed ATTR-CM. Fifty-one patients (44%) were treated with SGLT2i while 65 patients (56%) remained SGLT2i-naïve. Results: During a median follow-up of 2.6 (1.7–3.7) years, 38 patients (33%) died, of whom 11 patients (9%) received SGLT2i treatment and 27 patients (23%) were treatment-naïve. SGLT2i therapy was significantly associated with lower mortality (HR 0.457, 95%CI 0.227–0.922, p = 0.029). This association persisted after adjusting for age and sex (HR 0.479, 95%CI 0.235–0.977, p = 0.043) and after additional adjustment for eGFR, NT-proBNP, LVEF, and concomitant therapy with tafamidis (HR 0.328, 95%CI 0.141–0.760, p = 0.009). However, when potential immortal time bias was considered, this association lost statistical significance (HR 1.075, 95%CI 0.524–2.206, p = 0.843). No significant associations between SGLT2i therapy and worsening heart-failure hospitalization or cardiovascular mortality were observed. Conclusions: In crude analysis, SGLT2i therapy associates with better survival in patients with ATTR-CM. However, after adjustment for immortal time, this association becomes statistically insignificant. Hence, to draw final conclusions on the effectiveness of SGLT2i therapy in these patients, a randomized controlled trial is warranted. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Figure 1

12 pages, 617 KiB

Open AccessArticle

Baseline Predictors of Adverse Outcomes for Transthyretin Amyloidosis Cardiomyopathy Patients Treated and Untreated with Tafamidis: A Canadian Referral Center Experience

by Karan Shahi, Robert J. H. Miller, Steven Dykstra, Yuanchao Feng, Jonathan G. Howlett, Victor Jimenez-Zepeda, Jan Veenhuyzen, James A. White and Nowell M. Fine

J. Clin. Med. 2024, 13(18), 5490; https://doi.org/10.3390/jcm13185490 - 16 Sep 2024

Cited by 1 | Viewed by 1620

Abstract

Background: Tafamidis is a costly therapy that improves outcomes for patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), although significant knowledge gaps exist for predicting longer-term response to treatment. The purpose of this study was to examine baseline predictors of adverse outcomes and their association with tafamidis treatment in comparison with those untreated in a clinical cohort from a Canadian ATTR-CM referral center. Methods: Patients with a confirmed diagnosis of ATTR-CM were included. Multivariable modeling was used to identify baseline variables associated with the primary outcome of all-cause mortality and secondary outcomes of cardiovascular mortality or hospitalization. Cox proportional hazard and competing risk analyses were used, with tafamidis modeled as a time-varying covariate. Results: In total, 139 ATTR-CM patients were included, with a median age of 80.9 years [74.3–86.6 years], from 2011 to 2022. The mean follow-up was 2.9 ± 1.8 years. Eighty (55%) patients were treated with tafamidis. All-cause mortality and cardiovascular mortality alone were associated with the following baseline variables: age, clinical frailty scale, systolic blood pressure, renal function, and right ventricular size and function (all p < 0.05), with no identified interactions with tafamidis treatment. Only baseline renal function was associated with cardiovascular hospitalization (p < 0.05). Conclusion: Important baseline variables associated with adverse ATTR-CM disease outcomes included renal function, systolic blood pressure, frailty, and right ventricular size and function. The risk factors were independent of treatment with tafamidis. These findings may help improve risk stratification for determining eligibility for ATTR-CM therapies. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Figure 1

15 pages, 2153 KiB

Open AccessArticle

Effect of Timely Availability of TTR-Stabilizing Therapy on Diagnosis, Therapy, and Clinical Outcomes in ATTR-CM

by Stephan Dobner, Sara Zarro, Fabian Wieser, Mohammad Kassar, Bashir Alaour, Sebastian Wiedemann, Adam Bakula, Federico Caobelli, Stefan Stortecky, Christoph Gräni, Lukas Hunziker and Benedikt Bernhard

J. Clin. Med. 2024, 13(17), 5291; https://doi.org/10.3390/jcm13175291 - 6 Sep 2024

Cited by 1 | Viewed by 1709

Abstract

Background: Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective: To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods: Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. Results: Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3–28.9) to 2.4 (0.7–21.7) months, and from first presentation to therapy from 24.4 (10.7–46.8) to 11.8 (6.4–32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S’-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S’-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26–1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22–0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19–0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11–0.74); p = 0.009). Conclusions: Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Graphical abstract

Review

Jump to: Research

19 pages, 2075 KiB

Open AccessReview

Advancing Cardiac Amyloidosis Care Through Insights from Cardiopulmonary Exercise Testing

by Pietro Pugliatti, Giancarlo Trimarchi, Federico Barocelli, Fausto Pizzino, Francesco Di Spigno, Andrea Tedeschi, Maurizio Cusmà Piccione, Pierangela Irrera, Daniela Aschieri, Giampaolo Niccoli, Umberto Paradossi and Gianluca Di Bella

J. Clin. Med. 2024, 13(23), 7285; https://doi.org/10.3390/jcm13237285 - 29 Nov 2024

Cited by 1 | Viewed by 1992

Abstract

Cardiac amyloidosis, encompassing both transthyretin (ATTR) and light-chain (AL) types, poses considerable challenges in patient management due to its intricate pathophysiology and progressive course. This narrative review elucidates the pivotal role of cardiopulmonary exercise testing (CPET) in the assessment of these patients. CPET is essential for evaluating disease progression by measuring cardio-respiratory performance and providing prognostic insights. This functional test is crucial not only for tracking the disease trajectory, but also for assessing the effectiveness of disease-modifying therapies. Moreover, CPET facilitates the customization of therapeutic strategies based on individual patient performance, enhancing personalized care. By objectively measuring parameters such as peak oxygen uptake (VO₂ peak), ventilatory efficiency, and exercise capacity, clinicians can gain a deeper understanding of the degree of functional impairment and make informed decisions regarding treatment initiation, adjustment, and anticipated outcomes. This review emphasizes the importance of CPET in advancing personalized medicine approaches, ultimately striving to improve the quality of life and clinical outcomes for patients with cardiac amyloidosis. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Graphical abstract

20 pages, 4332 KiB

Open AccessReview

Epidemiological Changes in Transthyretin Cardiac Amyloidosis: Evidence from In Vivo Data and Autoptic Series

by Vincenzo Cianci, Alessio Cianci, Daniela Sapienza, Annalisa Cracò, Antonino Germanà, Antonio Ieni, Patrizia Gualniera, Alessio Asmundo and Cristina Mondello

J. Clin. Med. 2024, 13(17), 5140; https://doi.org/10.3390/jcm13175140 - 29 Aug 2024

Viewed by 1918

Abstract

Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)

► Show Figures

Journal Menu

Journal Browser

Advances in Diagnosis and Treatment of Amyloidosis

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI