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Journal of Comparative Effectiveness... Apr 2022Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to... (Review)
Review
Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to evaluate the current evidence base in AL amyloidosis. Literature searches on clinical, health-related quality of life, economic and resource use evidence were conducted using the Embase, MEDLINE and Cochrane databases as well as gray literature. This SLR yielded 84 unique studies from: five randomized controlled trials; 54 observational studies; 12 health-related quality of life studies, none with utility values; no economic evaluation studies; and 16 resource use studies, none with indirect costs. This SLR highlights a paucity of published literature relating to randomized controlled trials, utility values, economic evaluations and indirect costs in AL amyloidosis.
Topics: Cost-Benefit Analysis; Databases, Factual; Humans; Immunoglobulin Light-chain Amyloidosis; Publications; Quality of Life
PubMed: 35188424
DOI: 10.2217/cer-2021-0261 -
BMC Musculoskeletal Disorders Sep 2023Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple...
BACKGROUND
Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple organ systems. Diagnosis of ATTR amyloidosis is often delayed due to its heterogenous and non-specific presentation. This review investigates the association of musculoskeletal (MSK) manifestations with ATTR amyloidosis and the delay from the onset of these manifestations to the diagnosis of ATTR amyloidosis.
METHODS
This systematic review utilized Medline and EMBASE databases. Search criteria were outlined using a pre-specified patient, intervention, comparator, outcome, time, study (PICOTS) criteria and included: amyloidosis, ATTR, and MSK manifestations. Publication quality was assessed utilizing Joanna Briggs Institute (JBI) critical appraisal checklists. The search initially identified 7,139 publications, 164 of which were included. PICOTS criteria led to the inclusion of epidemiology, clinical burden and practice, pathophysiology, and temporality of MSK manifestations associated with ATTR amyloidosis. 163 publications reported on ATTR amyloidosis and MSK manifestations, and 13 publications reported on the delay in ATTR amyloidosis diagnosis following the onset of MSK manifestations.
RESULTS
The MSK manifestation most frequently associated with ATTR amyloidosis was carpal tunnel syndrome (CTS); spinal stenosis (SS) and osteoarthritis (OA), among others, were also identified. The exact prevalence of different MSK manifestations in patients with ATTR amyloidosis remains unclear, as a broad range of prevalence estimates were reported. Moreover, the reported prevalence of MSK manifestations showed no clear trend or distinction in association between ATTRv and ATTRwt amyloidosis. MSK manifestations precede the diagnosis of ATTR amyloidosis by years, and there was substantial variation in the reported delay to ATTR amyloidosis diagnosis. Reports do suggest a longer diagnostic delay in patients with ATTRv amyloidosis, with 2 to 12 years delay in ATTRv versus 1.3 to 1.9 years delay in ATTRwt amyloidosis.
CONCLUSION
These findings suggest that orthopedic surgeons may play a role in the early diagnosis of and treatment referrals for ATTR amyloidosis. Detection of MSK manifestations may enable earlier diagnosis and administration of effective treatments before disease progression occurs.
Topics: Humans; Amyloidosis; Carpal Tunnel Syndrome; Checklist; Citric Acid; Delayed Diagnosis; Prealbumin
PubMed: 37740174
DOI: 10.1186/s12891-023-06853-5 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Cancer Cell International Jul 2022Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered... (Review)
Review
BACKGROUND
Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis.
METHODS
We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model.
RESULTS
Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62-69%), 30% (95% CI, 23-36%), 40% (95% CI, 33-46%), 17% (95% CI, 14-21%), and 77% (95% CI, 73-80%), respectively. Cardiac and renal responses were 41% (95% CI, 34-49%) and 43% (95% CI, 32-54%), respectively. 58% (95% CI, 49-66%) of patients achieved PFS one year or longer. 2.5% (range, 1-10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6-25.0%).
CONCLUSION
This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.
PubMed: 35788237
DOI: 10.1186/s12935-022-02635-6 -
Frontiers in Cardiovascular Medicine 2023Cardiac amyloidosis (CA) is primarily a restrictive cardiomyopathy in which the impairment of diastolic function is dominant. Despite this, the left ventricular ejection...
BACKGROUND
Cardiac amyloidosis (CA) is primarily a restrictive cardiomyopathy in which the impairment of diastolic function is dominant. Despite this, the left ventricular ejection fraction (LVEF) may be depressed in the late stage of the disease, but it poorly predicts prognosis in the earlier phases and does not represent well the pathophysiology of CA. Many echocardiographic parameters resulted important diagnostic and prognostic tools in patients with CA. Stroke volume (SV) and myocardial contraction fraction (MCF) may be obtained both with echocardiography and cardiac magnetic resonance (MRI). They reflect many factors intrinsically related to the pathophysiology of CA and are therefore potentially associated with symptoms and prognosis in CA.
OBJECTIVES
To collect and summarize the current evidence on SV and MCF and their clinical and prognostic role in transthyretin (TTR-CA).
METHODS AND RESULTS
We performed a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We searched the literature database for studies focusing on SV and MCF in patients with TTR-CA. We analysed the following databases: PUBMED, Cochrane Library, EMBASE, and Web of Science database. Fourteen studies were included in the review. Both SV and MCF have important prognostic implications and are related to mortality. Furthermore, SV is more related to symptoms than LVEF and predicts tolerability of beta-blocker therapy in TTR-CA. Finally, SV showed to be an excellent measure to suggest the presence of TTR-CA in patients with severe aortic stenosis.
CONCLUSION
Stroke volume and MCF are very informative parameters that should be routinely assessed during the standard echocardiographic examination of all patients with TTR-CA. They carry a prognostic role while being associated with patients' symptoms.
SYSTEMATIC REVIEW REGISTRATION
https://doi.org/10.17605/OSF.IO/ME7DS.
PubMed: 36776259
DOI: 10.3389/fcvm.2023.1085824 -
American Journal of Cardiovascular... 2022Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an... (Review)
Review
BACKGROUND
Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.
METHODS
This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction.
RESULTS
Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I=87%) compared with transthyretin negative group.
CONCLUSION
Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.
PubMed: 35873185
DOI: No ID Found -
European Journal of Nuclear Medicine... Dec 2023Transthyretin (ATTR) amyloidosis is a progressive protein misfolding disease with frequent cardiac involvement. This review aims to determine the value of PET in... (Review)
Review
PURPOSE
Transthyretin (ATTR) amyloidosis is a progressive protein misfolding disease with frequent cardiac involvement. This review aims to determine the value of PET in diagnosis, assessment of disease progression or treatment response and its relation to clinical outcome in follow-up of ATTR amyloid cardiomyopathy (ATTR-CM) patients.
METHODS
Medline, Cochrane Library, Embase and Web of Science databases were searched, from the earliest date available until December 2022, for studies investigating the use of PET in ATTR-CM patients. Studies containing original data were included, except for case reports. Risk of bias was assessed by QUADAS-2.
RESULTS
Twenty-one studies were included in this systematic review, investigating five different tracers: carbon-11 Pittsburgh compound B ([C]PIB), fluorine-18 Florbetaben ([F]FBB), fluorine-18 Florbetapir ([F]FBP), fluorine-18 Flutemetamol ([F]FMM) and fluorine-18 Sodium Fluoride (Na[F]F). In total 211 ATTR amyloidosis patients were included. A majority of studies concluded that [C]PIB, [F]FBP and Na[F]F can distinguish ATTR amyloidosis patients from controls, and that [C]PIB and Na[F]F, but not [F]FBP, can distinguish ATTR-CM patients from patients with cardiac light chain amyloidosis. Evidence on the performance of [F]FBB and [F]FMM was contradictory. No studies on the use of PET in follow-up were found.
CONCLUSION
[C]PIB, Na[F]F and [F]FBP can be used to diagnose cardiac amyloidosis, although [F]FBP may not be suitable for the distinction of different types of amyloid cardiomyopathy. No studies on PET in the follow-up of ATTR amyloidosis patients were found. Future research should focus on the use of these PET tracers in the follow-up of ATTR amyloidosis patients.
Topics: Humans; Prealbumin; Follow-Up Studies; Amyloidosis; Positron-Emission Tomography; Cardiomyopathies
PubMed: 37561144
DOI: 10.1007/s00259-023-06381-3 -
ESC Heart Failure Jun 2022Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged... (Review)
Review
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Contrast Media; Gadolinium; Humans; Prealbumin; Prospective Studies
PubMed: 35343098
DOI: 10.1002/ehf2.13884 -
ESC Heart Failure Aug 2023The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current availability of disease-modifying drugs, prognostic stratification is becoming fundamental to optimizing the cost-effectiveness of treatment, patient phenotyping, follow-up, and management. Peak VO and VE/VCO slope are currently the most studied CPET variables in clinical settings, and both demonstrate substantial, independent prognostic value in several cardiovascular diseases. We aim to study the association of peak VO and VE/VCO slope with prognosis in patients with CA.
METHODS AND RESULTS
We performed a systematic review and searched for clinical studies performing CPET for prognostication in patients with transthyretin-CA and light-chain-CA. Studies reporting hazard ratio (HR) for mortality and peak VO or VE/VCO slope were further selected for quantitative analysis. HRs were pooled using a random-effect model. Five studies were selected for qualitative and three for quantitative analysis. A total of 233 patients were included in the meta-analysis. Mean peak VO resulted consistently depressed, and VE/VCO slope was increased. Our pooled analysis showed peak VO (pooled HR 0.89, 95% CI 0.84-0.94) and VE/VCO slope (pooled HR 1.04, 95% CI 1.01-1.07) were significantly associated with the risk of death in CA patients, with no significant statistical heterogeneity for both analyses.
CONCLUSIONS
CPET is a valuable tool for prognostic stratification in CA, identifying patients at increased risk of death. Large prospective clinical trials are needed to confirm this exploratory finding.
Topics: Humans; Exercise Test; Prospective Studies; Oxygen Consumption; Prognosis; Amyloidosis; Cardiomyopathies
PubMed: 37264762
DOI: 10.1002/ehf2.14406 -
Hellenic Journal of Cardiology : HJC =... 2022Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a large variation in the reported prevalence... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a large variation in the reported prevalence figures, due to differences in populations and diagnostic methods. We aimed to investigate the prevalence, risk factors and outcomes of concomitant CA and AS.
METHODS
We performed a systematic review and meta-analysis of the literature searched on MEDLINE, Embase, Scopus and CENTRAL. We analysed the prevalence of CA in patients with AS grouped according to the diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS were analysed in AS patients referred for surgical or transcatheter aortic valve replacement (AVR).
RESULTS
A total of 21 studies were included, involving 4,243 patients. The pooled prevalence of CA in patients with AS was 14.4%, with substantial heterogeneity. The pooled prevalence of AS in patients CA was 8.7%, with substantial heterogeneity. Patients with both AS and CA had higher all-cause mortality than those with AS or CA alone. In AS patients requiring AVR, CA was associated with increasing age, male sex, higher NT-proBNP levels, increased interventricular septal end diastole (IVSd) thickness and lower left ventricular ejection fraction. Concomitant AS and CA was associated with increased all-cause mortality and pacemaker implantation post-procedure. Study limitations included heterogeneity of the results and the fair to good quality of the studies published.
CONCLUSION
Overall, a substantial proportion of patients with AS may have CA, and they have poorer prognosis. A high degree of clinical suspicion is needed to identify the "red flags" and perform appropriate diagnostic imaging.
Topics: Amyloidosis; Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis Implantation; Humans; Male; Prevalence; Risk Factors; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left
PubMed: 34856378
DOI: 10.1016/j.hjc.2021.11.001