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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 -
Journal of Alzheimer's Disease : JAD 2022Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD).
OBJECTIVE
Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes.
METHODS
A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library.
RESULTS
Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15).
CONCLUSION
Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.
Topics: Alzheimer Disease; Amyloid; Amyloidogenic Proteins; Amyloidosis; Antibodies, Monoclonal; Cognitive Dysfunction; Humans
PubMed: 35275549
DOI: 10.3233/JAD-220046 -
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 -
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 -
Diagnostic and Interventional Radiology... Nov 2021Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our study aimed to systematically evaluate the accuracy of bone radiotracers for diagnosis and differentiation of TTR-CA via a systematic review and meta-analysis.
METHODS
We retrieved articles assessing the performance of bone tracer in diagnosing and differentiating TTR-CA from PubMed, the Cochrane Library, ScienceDirect, and DOAJ databases, dating up to 10 July 2020. The meta-analysis was conducted through Stata 16 software, and the risk of bias for the included studies was assessed by the QUADAS-2 tool. Moreover, we made a comprehensive review.
RESULTS
Fourteen articles were included in the systematic review, and 9 in the meta-analysis. The pooled sensitivity was 0.97 (95% confidence interval [95% CI] 0.85-0.99) with heterogeneity (I2=73.5, 95% CI 55.6-91.2), and the specificity was 0.92 (95% CI 0.82-0.96) with heterogeneity (I2=42.0, 95% CI 0.0-86.9). The pooled positive and negative likelihood ratios were 11.49 (95% CI 5.07-26.0) and 0.03 (95% CI 0.01-0.18), respectively. The diagnostic odds ratio was 341 (95% CI 53-2194), and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.94-0.97).
CONCLUSION
The findings evidence that the bone radiotracer is a valuable noninvasive approach that provides high accuracy for diagnosing TTR-CA and plays a modest role in differentiating TTR-CA from immunoglobulin amyloid light-chain cardiac amyloidosis. 99mTc-HMDP may be more accurate than 99mTc-PYP, 99mTc-DPD, and 18F-NaF in the TTR-CA detecting process, and 18F-NaF is a promising bone tracer to diagnose and differentiate TTR-CA.
Topics: Amyloidosis; Bone and Bones; Heart; Humans; Prealbumin; Radionuclide Imaging
PubMed: 34792038
DOI: 10.5152/dir.2021.20662 -
JAMA Neurology Jan 2022Transient focal neurological episodes (TFNEs) are a frequently overlooked presentation of cerebral amyloid angiopathy (CAA), a condition with prognostic implications... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Transient focal neurological episodes (TFNEs) are a frequently overlooked presentation of cerebral amyloid angiopathy (CAA), a condition with prognostic implications that are still not well described.
OBJECTIVE
To perform a systematic review and meta-analysis to examine the factors associated with incident lobar intracerebral hemorrhage (ICH) and death in patients with CAA presenting with TFNEs.
DATA SOURCES
A systematic review and individual participant meta-analysis including (1) a hospital-based cohort and (2) the results obtained from a systematic search performed in MEDLINE and Embase completed in December 2019.
STUDY SELECTION
Included studies were observational reports of TFNEs. Patient-level clinical, imaging, and prognostic data were required for inclusion. For aggregate data studies, patient-level data were requested. Disagreements were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines by 4 independent reviewers. The quality of reports was determined based on the modified Pearson Case Report Quality Scale.
MAIN OUTCOMES AND MEASURES
The clinical characteristics of TFNEs, neuroimaging features, and use of antithrombotics during follow-up were considered exposures. The predefined main outcomes were lobar ICH and risk of death during follow-up.
RESULTS
Forty-two studies and 222 CAA-associated TFNE cases were included from the initial 1612 records produced by the systematic search; 26 additional patients (11 men [42.3%]; mean [SD] age, 77 [8] years) were provided by the hospital-based cohort. A total of 108 TFNEs (43.5%) consisted of motor symptoms. Convexity subarachnoid hemorrhage and cortical superficial siderosis were detected in 193 individuals (77.8%) and 156 individuals (62.9%) in the systematic search and hospital-based cohort, respectively. Follow-up duration could be obtained in 185 patients (median duration, 1 year [IQR, 0.8-2.5 years]). During follow-up, symptomatic lobar ICH occurred in 76 patients (39.4%). Motor symptoms (odds ratio, 2.08 [95% CI, 1.16-3.70]) at baseline and antithrombotic use during follow-up (odds ratio, 3.61 [95% CI, 1.67-7.84]) were associated with an increase in risk of lobar ICH. A total of 31 patients (16.5%) died during follow-up; lobar ICH during follow-up and cortical superficial siderosis were the main risk factors for death (odds ratio, 3.01 [95% CI, 1.36-6.69]; odds ratio, 3.20 [95% CI, 1.16-8.91], respectively).
CONCLUSIONS AND RELEVANCE
Patients presenting with CAA-associated TFNEs are at high risk of lobar ICH and death. Motor TFNEs and use of antithrombotics after a TFNE, in many cases because of misdiagnosis, are risk factors for ICH, and therefore accurate diagnosis and distinguishing this condition from transient ischemic attacks is critical.
Topics: Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cohort Studies; Humans; Ischemic Attack, Transient; Risk Factors
PubMed: 34779831
DOI: 10.1001/jamaneurol.2021.3989 -
Oxidative Medicine and Cellular... 2021Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still... (Meta-Analysis)
Meta-Analysis
Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from and studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences ( < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Fermentation; Humans; Immunomodulating Agents; Kefir; Milk
PubMed: 34745425
DOI: 10.1155/2021/9081738 -
Annals of the Rheumatic Diseases Jan 2022To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
OBJECTIVES
To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
METHODS
According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting.
RESULTS
We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.
Topics: Antibodies, Monoclonal, Humanized; Azetidines; Consensus Development Conferences as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Immunomodulating Agents; Immunomodulation; Janus Kinase Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 34620584
DOI: 10.1136/annrheumdis-2021-221366 -
BMC Cardiovascular Disorders Oct 2021Noninvasive myocardial imaging modalities, such as cardiac magnetic resonance (CMR), single photon emission computed tomography (SPECT), and Positron emission tomography... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Noninvasive myocardial imaging modalities, such as cardiac magnetic resonance (CMR), single photon emission computed tomography (SPECT), and Positron emission tomography (PET), are well-established and extensively used to detect cardiac amyloid (CA). The purpose of this study is to directly compare CMR, SPECT, and PET scans in the diagnosis of CA, and to provide evidence for further scientific research and clinical decision-making.
METHODS
PubMed, Embase, and Cochrane Library were searched. Studies used CMR, SPECT and/or PET for the diagnosis of CA were included. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), their respective 95% confidence intervals (CIs) and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated. Quality assessment of included studies was conducted.
RESULTS
A total of 31 articles were identified for inclusion in this meta-analysis. The pooled sensitivities of CMR, SPECT and PET were 0.84, 0.98 and 0.78, respectively. Their respective overall specificities were 0.87, 0.92 and 0.95. Subgroup analysis demonstrated that Tc-HMDP manifested the highest sensitivity (0.99). Tc-PYP had the highest specificity (0.95). The AUC values of Tc-DPD, Tc-PYP, Tc-HMDP were 0.89, 0.99, and 0.99, respectively. PET scan with C-PIB demonstrated a pooled sensitivity of 0.91 and specificity of 0.97 with an AUC value of 0.98.
CONCLUSION
Our meta-analysis reveals that SEPCT scans present better diagnostic performance for the identification of CA as compared with other two modalities.
Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Cardiomyopathies; Clinical Decision-Making; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon
PubMed: 34620092
DOI: 10.1186/s12872-021-02292-z -
Circulation. Genomic and Precision... Oct 2021The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly...
BACKGROUND
The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly develop a cardiomyopathy (variant transthyretin amyloidosis cardiomyopathy) phenotype. Yet, there are conflicting data on the prevalence and outcomes of p.Val142Ile variant carriers.
METHODS
We performed a systematic review of the prevalence and outcomes of p.Val142Ile variant transthyretin amyloidosis cardiomyopathy among subjects of African descent. We found 62 relevant articles after searching the MEDLINE databases from 1980 to 2020 that reported data for ≈150 000 subjects.
RESULTS
The reported worldwide prevalence of the p.Val142Ile variant is 0.3% to 1.6% in the general population. Among people of African descent, the reported prevalence from all studies ranges from 1.1% to 9.8%, but for studies with >1000 subjects, it is 3% to 3.5%. The prevalence of the p.Val142Ile variant in a region is dependent on the reported percentage of subjects who are of African descent in that region. p.Val142Ile variant transthyretin amyloidosis cardiomyopathy typically presents in the seventh to eighth decade of life and the majority of cases reported were male, with 25% to 38% diagnosed with atrial fibrillation. It was associated with a longitudinally worse quality of life and a lower adjusted survival compared with other types of transthyretin amyloidosis cardiomyopathy.
CONCLUSIONS
The p.Val142Ile variant is the most common variant of the transthyretin gene with most carriers being of African descent. The true penetrance is unknown but the p.Val142Ile variant is associated with increased rates of incident heart failure and portends a lower overall survival. Increased awareness could lead to earlier diagnosis and improved heart failure outcomes among those of African descent, which is of increasing importance given the advent of novel therapeutics for this disease.
Topics: Amino Acid Substitution; Amyloid Neuropathies, Familial; Cardiomyopathies; Female; Humans; Male; Mutation, Missense; Prealbumin; Prevalence; Risk Factors; Sex Factors
PubMed: 34461737
DOI: 10.1161/CIRCGEN.121.003356