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Cardiac amyloidosis is a disease characterised by the accumulation of amyloid protein in the heart tissue. There are several types of amyloidosis, but the most common types affecting the heart are ATTR amyloidosis (caused by transthyretin protein) and AL amyloidosis (caused by abnormal immunoglobulin light chains). Cardiac amyloidosis causes typical signs and symptoms of heart failure. Diagnosis involves a combination of imaging tests such as echocardiography and cardiac magnetic resonance imaging, as well as nuclear imaging scans and tissue biopsies to confirm the presence of amyloid deposits in the heart. Treatment of cardiac amyloidosis depends on the type and severity of the disease and includes medications to manage symptoms as well as treatments targeting the underlying cause of amyloidosis. Importantly, cardiac amyloidosis is a serious condition requiring specialised care from a multidisciplinary team including cardiologists and haematologists as well as other specialists familiar with the management of this rare disease. This is crucial, as early diagnosis and treatment are important for improving outcomes.

Background: Macular amyloidosis (MA) could be of cosmetic concern with a significant psychological impact for patients, and its treatment is challenging., Aim of the Work: To compare the efficacy and safety of combined fractional CO 2 laser with dimethyl sulfoxide (DMSO) 50% versus fractional CO 2 laser alone in the treatment of macular amyloidosis., Patients and Methods: Twenty patients with macular amyloidosis were treated with monthly session of fractional CO 2 laser only in one side of the lesion (area A), and fractional laser followed by application of DMSO 50% solution in the other side of the lesion (area B). All patients were evaluated clinically, by dermoscope and histopathology before and 3 months after the end of 4 treatment sessions., Results: Both treatments showed significant decrease of pigmentation after treatment (p < 0.001). There was non-significant decrease in rippling on both sides (p = 0.06). The median itching score dropped significantly after treatment from 9 to 3.5 in area A (laser only) and to 2 in area B (laser and DMSO), with non-significant difference between both areas (P = 0.244). Dermoscopic features after treatment showed fading and decreasing in multiple features in both areas A and B, with non-significant difference between the 2 areas. Histopathologically, there was significant reduction in the amyloid deposition after treatment in both areas A and B without significant difference between both areas., Conclusion: both fractional CO 2 laser combined with topical DMSO 50% and fractional CO 2 laser alone are safe and effective treatment options for MA with significant clinical improvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is a genome editing tool widely used in biological research and clinical therapeutics. Natural human genetic variations, through altering the sequence context of CRISPR-Cas9 target regions, can significantly affect its DNA repair outcomes and ultimately lead to different editing efficiencies. However, these effects have not been systematically studied, even as CRISPR-Cas9 is broadly applied to primary cells and patient samples that harbor such genetic diversity. Here, we present comprehensive investigations of natural genetic variations on CRISPR-Cas9 outcomes across the human genome. The utility of our analysis is illustrated in two case studies, on both preclinical discoveries of CD33 knockout in chimeric antigen receptor-T cell therapy and clinical applications of transthyretin (TTR) inactivation for treating TTR amyloidosis. We further expand our analysis to genome-scale, population-stratified common variants that may lead to gene editing disparity. Our analyses demonstrate pitfalls of failing to account for the widespread genetic variations in Cas9 target selection and how they can be effectively examined and avoided using our method. To facilitate broad access to our analysis, a web platform CROTONdb is developed, which provides predictions for all possible CRISPR-Cas9 target sites in the coding and noncoding regulatory regions, spanning over 5.38 million guide RNA targets and 90.82 million estimated variant effects. We anticipate CROTONdb having broad clinical utilities in gene and cellular therapies.

Amyloidosis are rare protein misfolding and deposition diseases which, with very few exceptions, are treatable easily nowadays. The prognosis depends on the form of amyloidosis, which is particularly unfavorable for heart involvement that is diagnosed too late. Patients die within months to a few years or suffer irreversible loss of function of the affected organs. Once the diagnosis has been made, treatment should be started without delay. Amyloidosis centers offer support in the diagnosis and development as well as clinical trials of an optimal therapy concept., Competing Interests: Prof. Hegenbart: Honorarium for talks: Janssen, Pfizer, Alnylam, Akcea, Prothena, Astra Zeneca (honorary received by institution) Financial support of congress participation; Janssen, Prothena, Pfizer Advisory Boards: Pfizer, Prothena, Janssen, Alexion, Alnylam Financial sponsoring of Amyloidosis Registry: Janssen, Prothena (received by institution) Prof. Schönland: Consultant/Adviserfor and received travel grant, honoraria, and research funding from Janssen and Prothena; received research funding from Sanofi; received honoraria from Pfizer and Takeda; and is an adviser for Telix; received travel grants from Binding Site, Celgene, and Jazz., (Thieme. All rights reserved.)

Purpose: Localized gastrointestinal tract amyloidosis is uncommon and little is known regarding this entity. There is no current standard of care for the management of localized amyloidosis. The objective of this study was to evaluate the characteristics, available treatments, outcomes and surveillance of these patients., Methods: We conducted a systematic review of cases reported in the literature from 1962 to 2021. Patients with gastrointestinal amyloidosis reported in English literature were included in the analysis. We described and summarized the patient's characteristics, treatments, clinical presentations, outcomes and surveillance., Results: The systematic review of reported clinical cases included 62 patients. In these patients, the most common site of amyloid deposition was the stomach (42%). The median age of diagnosis is 64.4 years old; there is a 2:1 prevalence among males (63%) to females (37%); abdominal pain is the most common type of presentation (41%), although patients could also be asymptomatic. There is a high curative rate (100%) with resection alone. Among patients treated with a type of systemic therapy, 80% achieved a complete response. The minority of cases reported a type of surveillance post treatment, and among those 62% pursued serial clinical evaluations alone., Conclusion: To our knowledge, this is the first and largest systematic review of the literature in gastrointestinal tract amyloidosis. This is more common among males and seems to have an excellent curative rate (100%) with surgery alone. Systemic therapy is an option for those with non-resectable amyloidomas. Serial clinical evaluations should be part of the standard surveillance care in these patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This case report describes a rare and interesting case of a patient with multiple myeloma complicated with light chain (LC) cast nephropathy and focal amyloidosis. The patient presented with acute kidney injury, anaemia and bone lesions. The diagnosis was confirmed by bone marrow biopsy, serum and urine electrophoresis and kidney biopsy. The patient was treated with isazomil, pomalidomide and dexamethasone combination chemotherapy, followed by autologous stem cell transplantation. The patient achieved clinical remission, stable renal function and improved serum lambda free LC levels. This case highlights the challenges and advances in the diagnosis and treatment of this condition., (© 2024 Asian Pacific Society of Nephrology.)

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by the deposition of amyloid fibrils in the myocardium. It manifests in two primary subtypes: transthyretin cardiac amyloidosis (ATTR) and immunoglobulin light chain cardiac amyloidosis (AL). ATTR is further classified into wild-type and hereditary based on transthyretin gene mutation. Advances in diagnostics and therapeutics have transformed CA from a rare and untreatable condition to a more prevalent and manageable disease. Noninvasive diagnostic tools such as electrocardiography, echocardiography, and cardiac magnetic resonance can raise suspicion for CA; bone scintigraphy can non-invasively confirm ATTR, while AL necessitates histological confirmation. The severity of ATTR and AL can be assessed through serum biomarker-based staging. Treatment approaches differ, ranging from silencing or stabilizing transthyretin and degrading amyloid fibrils in ATTR to employing anti-plasma cell therapies and autologous stem cell transplantation in AL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within the myocardium. Beyond heart failure, patients with cardiac amyloidosis commonly present with arrhythmias and conduction system disorders. Atrial fibrillation is observed in up to 80% of patients at the time of diagnosis, with patients typically maintaining normal heart rates due to concurrent atrioventricular nodal disease. The thromboembolic risk is particularly high in patients with cardiac amyloidosis, and left atrial thrombi have been observed even in the absence of atrial fibrillation. Conduction system diseases are also highly prevalent, often necessitating permanent pacemaker implantation. The use of implantable defibrillators in this population remains controversial. This overview of published data and therapeutic strategies related to arrhythmias and conduction system disorders aims to assist readers in decision-making in complex clinical scenarios., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a clonal non-proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood-nerve barrier disruption. Clinically, amyloid neuropathy is manifested as a length-dependent sensory predominant neuropathy associated with generalized autonomic failure. Small unmyelinated nerves are involved early and prominently in early-onset Val30Met ATTRv, whereas other ATTRv and light-chain amyloidosis often present with large- and small-fiber involvement. Nerve conduction studies, quantitative sudomotor axon testing, and intraepidermal nerve fiber density are useful tools to evaluate denervation. Amyloid deposition can be demonstrated by tissue biopsy of the affected organ or surrogate site, as well as bone-avid radiotracer cardiac imaging. Treatment of light-chain amyloidosis has been revolutionized by monoclonal antibodies and stem cell transplantation with improved 5-year survival up to 77%. Novel gene therapy and transthyretin stabilizers have revolutionized treatment of ATTRv, improving the course of neuropathy (less change in the modified Neuropathy Impairment Score + 7 from baseline) and quality of life. With great progress in amyloidosis therapies, early diagnosis and presymptomatic testing for ATTRv family members has become paramount. ANN NEUROL 2024;96:423-440., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA 2 DS 2 -VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diagnosis and treatment of cardiac amyloidosis have rapidly evolved over the past decade by harnessing mechanisms of disease pathogenesis. Cardiac amyloidosis is caused by myocardial deposition of fibrils formed by misfolded proteins, namely transthyretin (ATTR) and immunoglobulin light chains (AL). Advances in noninvasive imaging have revolutionized diagnosis of ATTR cardiomyopathy (CM). Novel treatments for ATTR-CM utilize a range of therapeutic techniques, including protein stabilizers, interfering RNA, gene editing, and monoclonal antibodies. AL-CM, primarily driven by plasma cell dyscrasias, requires treatment with chemotherapy and consideration for autologous stem cell transplant. These incredible advances aim to improve patient outcomes in cardiac amyloidosis., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid., Recent Findings: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy., (© 2024. The Author(s).)

Amyloidosis is a rare, heterogeneous group of diseases characterized by extracellular infiltration and deposition of misfolded fibrils in different organs and tissues. A timely diagnosis is important as it can improve outcome. Echocardiography has emerged as a powerful tool to prompt suspicion and refer patients to second-level evaluation to reach a definitive diagnosis. In this scenario, new echo techniques offer new insight into the cardiac amyloidosis (CA) pathophysiology and clinical course. The present review aims to describe the developments in echocardiographic assessment of patients with suspected CA and it summarizes new available echocardiographic scores able to guide a definite diagnosis., Competing Interests: Disclosure G. Limongelli received unrestricted research grant from Pfitzer. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Amyloidosis is a systemic disease due to the accumulation of misfolded amyloid fibrils that damage the heart and worsen the prognosis. Heart failure (HF), a condition frequently linked with an advanced stage of this disease, is the most prevalent clinical manifestation that leads to its diagnosis. However, due to the growing awareness of the occurrence of cardiac amyloidosis (CA), it is now possible to perform an early diagnosis and have a positive impact on its natural course. This study aims to highlight the most compelling issues concerning patients' clinical management with HF and CA., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several pathophysiological hypotheses have been proposed regarding the causes of this association, neither of which fully substantiated in practice. The key to detect the coexistence of cardiac amyloidosis and aortic valve stenosis lies in clinical suspicion. It is possible to hypothesize concurrent cardiac amyloidosis in patients with aortic valve stenosis with the aid of clinical, electrocardiographic, echocardiographic, and extracardiac "red flags". Subsequent non-invasive diagnostic steps are often sufficient to establish a definitive diagnosis. The early diagnosis of this condition is pivotal since the presence of dual pathology worsens patient's prognosis, especially without intervention. Available data on treatment show a better outcome in terms of survival and cardiovascular events in patients undergoing percutaneous correction of valvular heart disease rather than medical therapy alone, regardless of the presence of cardiac amyloidosis. Furthermore, it seems that cardiac amyloidosis does not impact survival after transcatheter aortic valve replacement, even if higher rates of rehospitalizations have been described. Indeed, percutaneous treatment of valvular heart disease is currently considered the primary therapeutic option. Subsequently a disease-modifying treatment for transthyretin amyloidosis may be considered in order to delay disease progression and improve outcomes, even if specific data are still lacking.

Competing Interests: Disclosures None.

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis., Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed., (© 2024. The Author(s).)

Cardiac amyloidosis multidisciplinary team (MDT). We propose the creation of a multidisciplinary team (MDT) for cardiac amyloidosis in which internal medicine physicians could take a lead role in coordinating other specialists involved in patient care. Created with BioRender.com., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of β 2 -microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β 2 -microglobulin (β2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis., Methods: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aβ2M amyloid fibril formation in vitro ., Results: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as β2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aβ2M amyloid fibril formation., Conclusions: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aβ2M amyloidogenesis by reducing the amyloid-related proteins.

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical for disease management. These technologies provide extensive insights into the specific proteins involved, allowing for more targeted treatment approaches and better patient results. Despite these advances, problems remain, owing to the heterogeneous composition of amyloid proteins and the varying efficacy of treatments based on amyloid type. Access to sophisticated diagnostics and therapy varies greatly, highlighting the global difference in renal amyloidosis management. Future research is needed to investigate next-generation sequencing and gene-editing technologies, like clustered regularly interspaced short palindromic repeats (CRISPR), which promise more profound insights into the genetic basis of amyloidosis.

The prevalence of amyloidosis has been increasing, driven by a combination of improved awareness, evolution of diagnostic pathways, and effective treatment options for both transthyretin and light chain amyloidosis. Due to the complexity of amyloidosis, centralised expert providers with experience in delineating the nuances of confirmatory diagnosis and management may be beneficial. There are many potential benefits of a centre of excellence designation for the treatment of amyloidosis including recognition of institutions that have been leading the way for the optimal treatment of this condition, establishing the expectations for any centre who is engaging in the treatment of amyloidosis and developing cooperative groups to allow more effective research in this disease space. Standardising the expectations and criteria for these centres is essential for ensuring the highest quality of clinical care and community education. In order to define what components are necessary for an effective centre of excellence for the treatment of amyloidosis, we prepared a survey in cooperation with a multidisciplinary panel of amyloidosis experts representing an international consortium. The purpose of this position statement is to identify the essential elements necessary for highly effective clinical care and to develop a general standard with which practices or institutions could be recognised as a centre of excellence., Competing Interests: Competing interests: JM is a consultant (modest) for Bridgebio. SM has received speaker fees from AstraZeneca, Pfizer, Janssen, Astellas, Bayer and Edwards, and is on advisory boards for Pfizer and AstraZeneca. SC is employed by International Cardio-Oncology Society (IC-OS), a non-profit company. IL is the founder of the Amyloidosis Research Consortium. DL is a member of a data safety board for Intellia and a consultant for the IC-OS. All other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Amyloidosis is a systemic infiltrative disease characterized by deposition of misfolded proteins in tissues, notably affecting the heart. According to type of protein, various types are known with the most prevalent being light-chain and transthyretin amyloidosis. Prognosis is dismal with progression to severe heart failure without disease-modifying treatment. Latter having dramatically improved over the last decade, prompt diagnosis is of paramount importance. Recognition of early signs followed by multidisciplinary approach is essential for optimal patient management., Competing Interests: S. Hugelshofer a reçu un soutien financier de Pfizer et Alnylam (conseil consultatif et orateur invité), versé directement au fond de service de cardiologie du Centre hospitalier universitaire vaudois. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment., (© 2024 John Wiley & Sons Ltd.)

AL amyloidosis, derived from amyloidogenic immunoglobulin light chains, is a common type of systemic amyloidosis. Peripheral neuropathy has been identified in 10%-40% of patients with systemic AL amyloidosis. Definitive diagnosis requires tissue biopsies, including skin, fat, and gastrointestinal samples, as well as amyloid typing. Disease-modifying therapies have been shown to improve patient survival and prevent progressive organ dysfunction.

Background: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials., Methods and Results: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%)., Conclusions: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition., Competing Interests: Disclosures JLG reports consulting fees from Pfizer, Eidos/BridgeBio, Alnlyam, Intellia, Sarepta, and AstraZeneca; Grant support from Pfizer 67656485, Eidos/BridgeBio, Texas Health Resources Clinical Scholarship, and NHLBI R01 HL160892-01A1. MSM reports consulting fees from AstraZeneca, Akcea, Intellia, and Novo-Nordisk; grant support from NIH R01HL139671, Alnylam, Pfizer, Eidos, Prothena, and Ionis. FLR reports consulting fees from Attralus and grant support from Pfizer, Alnylam, and Akcea/Ionis. ARP reports grant support from Pfizer. MGK reports consulting fees from and advisory board membership in Pfizer, Eidos, Alnylam; Grant support: Pfizer, Alnylam, Eidos, Ionis, and Moleculin Biotech and speaker's bureau with Alnylam. YB reports grant support from Pfizer. BMD reports consulting fees from Anylam and Eidos. NMF reports consulting/speaker's fees and bureau/honoraria from Pfizer, Akcea/Ionis, Sobi, Alnylam, Sanofi-Genzyme, AstraZeneca, and Takeda; grant support from Pfizer, Akcea/Ionis, Servier, Takeda, Novartis, and Eidos. HG reports consulting fees from Amgen, Bayer, Merck, Pfizer, and ExpertConnect and grant support from Roche Diagnostics, Jana Care, Ortho Clinical, Novartis, Pfizer, Alnylam, Akcea/Ionis, and Eidos/BridgeBio and stock ownership in Eko; research payments for clinical endpoint committees from Baim INstitute for Clinical Research for Abbott, Siemens and Beckman Coulter and from ACI Clinical for Abbott Laboratories. DJ reports consulting fees from Alexion, Alleviant, Cytokinetics, Novo-Nordisk, Pfizer, Renovacor/Rocket, and Tenaya. JM reports consultingfees from Myocardial Solutions, Abbott, Longer Life Foundation, Children's Discovery Institue, Pfizer, BridgeBio, and Altathera. SSM reports speaker's fees from and Bureau/Advisory Board member of Alnylam. RCM reports consulting fees/honoraria from Pfizer and AstraZeneca. FHS reports grant support from Alnylam and Ionis. BS reports consulting fees from Alnylam and BridgeBio/Eidos and speaker's bureau fees from Pfizer. MU reports grant support from Ionis; advisory board membership with Alnylam, Cytokinetics, BridgeBio/Eidos; speaker's bureau with Pfizer, Alnylam, Akcea. JKP reports grant support from Alexion, Alnylam, AstraZeneca, BridgeBio/Eidos, Novo-Nordisk, and Pfizer; advisory board/speaker's bureau membership with Alnylam, CareDx, Eidos, Ionis, Natera, and Pfizer. All other authors have no financial relationships to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or hereditary variants, or immunoglobulin light chains misfolding. It is characterized by an increased left ventricular (LV) mass and diastolic dysfunction, which can lead to heart failure with preserved ejection fraction and/or conduction disturbances. The diagnosis is based on invasive pathology demonstration of amyloid deposits, or non-invasive criteria using advanced cardiovascular imaging techniques. Nevertheless, 12-lead electrocardiogram (ECG) remains of crucial importance in the assessment of patients with CA, since they can manifest peculiar features such as low QRS voltages, in discordance with the LV hypertrophy, but also pseudo-infarction patterns, sinus node dysfunction, atrioventricular blocks, premature supraventricular and ventricular beats, which support the presence of a myocardial disease. Great awareness of these common ECG characteristics of CA is needed to increase diagnostic performance and improve patient's outcome. In the present review, we discuss the current role of the ECG in the diagnosis and management of CA, focusing on the most common ECG abnormalities and rhythm disorders., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Cardiac amyloidosis (CA) has diverse and deleterious effects on the conductive system. Atrial fibrillation is by far the most common electrophysiological manifestation of CA and is associated with more mortality, morbidity, and hospitalizations. While AF increases the risk of thrombosis regardless of the CHA 2 DS 2 -VASc score, the risk of thromboembolism seems to be high even in CA patients without AF. AV Nodal disease is prevalent and may precede the diagnosis of CA. The incidence of ventricular arrhythmias remains disputed, and the role of implantable cardioverter defibrillator devices in CA patients is controversial. Newer therapies targeted against specific types of CA have been developed, but their effects on conductive system disease are not well studied., (Copyright © 2023. Published by Elsevier Inc.)

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA., Competing Interests: Conflicts of Interest NB: Novartis, Pfizer—research, Bristol Myers Squibb—advisory board. JLH: Pfizer—advisory board, clinical trials involvement. SDJG: Pfizer, BridgBio, Alexion/Astrazeneca, Ionis, Intellia, Attralus—honoria for speaking engagements, advisory board or steering committee payments, clinical trials involvement. PM: Jansen, Pfizer—research funding/clinical trials involvement. LT: Boehringer Ingelheim, Novartis, Sanofi Genzyme—advisory board, Jansen, Pfizer, Bayer—research funding. No relevant conflicts of interest to declare: DF, JG, DK, FK, KL, DR, HS, TS., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Introduction: Amyloid precursor protein (APP) transgenic mice are models of Alzheimer's disease (AD) amyloidosis, not all of AD. Diffuse, compacted, and vascular deposits in APP mice mimic those found in AD cases., Methods: Most interventional studies in APP mice start treatment early in the process of amyloid deposition, consistent with a prevention treatment regimen. Most clinical trials treat patients with established amyloid deposits in a therapeutic treatment regimen., Results: The first treatment to reduce amyloid and cognitive impairment in mice was immunotherapy. The APP mouse models not only predicted efficacy, but presaged the vascular leakage called ARIA. The recent immunotherapy clinical trials that removed amyloid and slowed cognitive decline confirms the utility of these early APP models when used in therapeutic designs., Discussion: New mouse models of AD pathologies will add to the research armamentarium, but the early models have accurately predicted responses to amyloid therapies in humans., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Disease Overview: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS.", Diagnosis: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy., Prognosis: N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively., Therapy: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine., Future Challenges: Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway., (© 2023 Wiley Periodicals LLC.)

Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and β-amyloid peptide (Aβ) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer's disease, respectively. Though crenezumab, an anti-Aβ antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both Aβ42 oligomers and AL fibrils with high binding affinities. It is capable of reversing Aβ42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.

La amiloidosis es una enfermedad heterogénea, de origen hereditario o adquirido, que se caracteriza por el depósito anormal de proteínas fibrilares en diversos tejidos. Esta enfermedad puede manifestarse de manera localizada o sistémica, lo que genera una amplia variabilidad en su presentación clínica y, frecuentemente, retrasa el diagnóstico. Por ello, es fundamental la identificación temprana de los signos y síntomas para mejorar el pronóstico. El primer posicionamiento mexicano sobre la amiloidosis cardíaca tiene como objetivo resumir las principales características de la enfermedad y sus subtipos, identificando datos de alarma que incrementen la sospecha de su presencia. Además, busca ofrecer un algoritmo diagnóstico que integre los estudios de imagen y de laboratorio disponibles en nuestro país, con el fin de simplificar la toma de decisiones y llegar a un diagnóstico de manera rápida, práctica y actualizada, basado en recomendaciones sustentadas en evidencia científica. Una vez confirmado el diagnóstico, se abordan los distintos retos terapéuticos, tanto farmacológicos como no farmacológicos, ya que los pacientes no responden al tratamiento convencional de insuficiencia cardíaca. Por ello, el tratamiento debe ser individualizado para cada paciente, teniendo en cuenta la presencia de otras comorbilidades. Finalmente, se presentan los principales factores pronósticos que guiarán un tratamiento adecuado, incluyendo los resultados del asesoramiento genético., (Copyright: © 2024 Permanyer.)

Systemic amyloidosis is a rare protein misfolding and deposition condition that causes slow organ failure. Each of the more than 15 exclusive sorts of systemic amyloidosis, which encourage amyloid production and tissue deposition, is introduced by a unique precursor protein. Amyloidosis can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin, and soft tissues. It can either be acquired or hereditary. Insidious and doubtful signs often cause a put-off in diagnosis. In the closing decade, noteworthy progressions have been made in the identity, prediction, and handling of amyloidosis. Shotgun proteomics based on mass spectrometry has revolutionized amyloid typing and enabled the identification of novel amyloid forms. It is critical to correctly identify the precursor protein implicated in amyloidosis because the kind of protein influences the proper treatment strategy. Cardiac amyloidosis is a disorder characterized by the systemic accumulation of amyloid protein in the myocardium's extracellular space, which causes a variety of symptoms. The buildup of amyloid aggregates precipitates myocardial thickening and stiffening, culminating in diastolic dysfunction and, in due course, heart failure. We examine every kind of systemic amyloidosis in this text to offer practitioners beneficial equipment for diagnosing and treating those unusual diseases. This review presents a comprehensive analysis of cardiac amyloidosis and consolidates current methods for screening, diagnosis, evaluation, and treatment alternatives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Amyloidosis is a heterogeneous disorder characterized by abnormal protein aggregate deposition that often leads to kidney involvement and end-stage kidney disease. With advancements in diagnostic techniques and treatment options, the prevalence of patients with amyloidosis requiring chronic dialysis has increased. Kidney transplantation is a promising avenue for extending survival and enhancing quality of life in these patients. However, the complex and heterogeneous nature of amyloidosis presents challenges in determining optimal referral timing for transplantation and managing post-transplantation course. This review focuses on recent developments and outcomes of kidney transplantation for amyloidosis-related end-stage kidney disease. This review also aims to guide clinical decision-making and improve management of patients with amyloidosis-associated kidney disease, offering insights into optimizing patient selection and post-transplant care for favorable outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A family of maladies known as amyloid disorders, proteinopathy, or amyloidosis, are characterized by the accumulation of abnormal protein aggregates containing cross-β-sheet amyloid fibrils in many organs and tissues. Often, proteins that have been improperly formed or folded make up these fibrils. Nowadays, most treatments for amyloid illness focus on managing symptoms rather than curing or preventing the underlying disease process. However, recent advances in our understanding of the biology of amyloid diseases have led to the development of innovative therapies that target the emergence and accumulation of amyloid fibrils. Examples of these treatments include the use of small compounds, monoclonal antibodies, gene therapy, and others. In the end, even if the majority of therapies for amyloid diseases are symptomatic, greater research into the biology behind these disorders is identifying new targets for potential therapy and paving the way for the development of more effective treatments in the future., (Copyright © 2024. Published by Elsevier Inc.)

Background: Conventional right ventricle (RV) pacemaker stimulation has been associated with worse clinical outcomes in patients with cardiac amyloidosis (CA). Left bundle branch area pacing (LABPP) has been suggested as a promising alternative. We sought to assess the safety, feasibility, and outcomes of LABPP in patients with CA., Methods: We retrospectively analyzed echocardiography and pacing parameters and clinical outcomes in 23 consecutive patients with CA and LBBAP implanted from June 2020 to October 2022., Results: LBBAP was successfully performed in 22 over 23 patients (19 male, 78.6 ± 11.7 years, 20 ATTR, mean LVEF 45.5 ± 16.2%). After the procedure, 9 patients showed Qr pattern and 11 a qR pattern in V1 on ECG. Average procedure time was 67 ± 28 min. After 7.7 ± 5.2 months follow-up, no procedure-related complications had occurred. Although, a significant reduction in QRS width (p = .001) was achieved, we did not observe significant changes in LVEF and Nt ProBNP at 6 months of follow-up. Pacing parameters were stable during follow-up: LBB capture threshold and R wave amplitude were 1.0 ±  0.5 V and 10.6 ± 6.0 mV versus 0.8 ±  0.1 V, p = .21 and 10.6 ± 5.1 mV (p = .985) at follow up., Conclusion: LBBAP is safe and feasible pacing technique for patients with CA. LBBAP is associated with significant narrowing of QRSd without worsening in LVEF and Nt-proBNP., (© 2023 Wiley Periodicals LLC.)

Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped under three main headings: immunoglobulin light chain (AL) amyloidosis that is dependent on amyloidogenic monoclonal light chain production; hereditary Transthyretin (TTR) amyloidosis that results from accumulation of mutated TTR; and wild-type (non-hereditary) TTR amyloidosis formerly known as senile amyloidosis. Although all three types cause morbidity and mortality due to severe heart failure when untreated, they contain differences in their pathogenesis, clinical findings, and treatment. In this article, the clinical features, pathogenesis, diagnosis, and treatment methods of cardiac amyloidosis will be explained with an overview, and an awareness will be raised in the diagnosis of this disease.

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A" (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Solitary plasmacytoma is a rare, localized malignancy. Bone localizations are the most common. Extramedullary plasmacytomas are much rarer. They are most often in the upper respiratory tract and can be complicated by amyloidosis. Here is an original report of a mediastinal extramedullary plasmacytoma revealed by type AA renal amyloidosis., Case Presentation: We present the case of a 52-year-old patient with mediastinal extramedullary plasmocytoma diagnosed by renal failure due to type AA renal amyloidosis. Treatment was based on surgery with chemotherapy based on prednisone and melphalan. The patient presented end-stage renal failure that required hemodialysis at discharge., Conclusion: Extramedullary plasmacytoma is a rare tumour that may be associated with amyloidosis, usually type AL. To our knowledge, its association with AA amyloidosis has not been reported in the literature. Treatment is based on surgery combined with radiotherapy or chemotherapy.