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Journal of Clinical Medicine Sep 2023The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone... (Review)
Review
BACKGROUND
The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings.
METHODS
A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values.
RESULTS
Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7-1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men.
CONCLUSIONS
The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.
PubMed: 37685765
DOI: 10.3390/jcm12175698 -
Journal of Nuclear Cardiology :... Dec 2023Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy.
METHODS
We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling.
RESULTS
Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity.
CONCLUSIONS
Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.
Topics: Humans; Prealbumin; Amyloid Neuropathies, Familial; Tomography, X-Ray Computed; Radionuclide Imaging; Cardiomyopathies
PubMed: 37226006
DOI: 10.1007/s12350-023-03297-1 -
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 Cardiology May 2024This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse outcomes.
METHODS
We performed a comprehensive search from January 1, 2000 to October 20, 2023. Studies examining BB use and tolerance or the relationship between BB use and outcomes in patients with CA were included. Pooled adjusted hazard ratios (aHRs) for all-cause mortality were calculated using random- and fixed-effects models.
RESULTS
Eight observational studies involving 4002 patients with CA (87.5% with transthyretin CA [ATTR-CA] and 12.5% with immunoglobulin light chain CA [AL-CA]) were assessed. BBs were used by 52.5% of the patients. However, 26.3% of the patients discontinued BBs because of hypotension, bradycardia, or fatigue. Regarding the association between BB use and all-cause death, four studies were identified that included 2874 patients with ATTR-CA and 16 patients with AL-CA. The meta-analysis revealed no apparent relationship between BB use and all-cause mortality (pooled aHR = 0.78, 95% confidence interval (CI) = 0.40-1.51). Two studies on patients with ATTR-CA found no impact of BB use on all-cause mortality in the subgroup with left ventricular ejection fraction (LVEF) > 40%, but conflicting results exist for those with LVEF ≤40% (pooled aHR = 0.78, 95% CI = 0.40-1.54).
CONCLUSION
The limited number of observational studies that predominantly enrolled patients with ATTR-CA showed that BBs were used in almost half of the patients with CA, with varying tolerability. However, no significant association was observed between BB use and all-cause mortality.
Topics: Humans; Amyloid Neuropathies, Familial; Stroke Volume; Ventricular Function, Left; Immunoglobulin Light-chain Amyloidosis; Prealbumin; Cardiomyopathies
PubMed: 38278490
DOI: 10.1016/j.ijcard.2024.131813 -
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 -
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 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 -
The Journal of Investigative Dermatology Jun 2024A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles...
A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 sequence variants from 2016 to August 2023 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data from 177 patients from 65 articles were retrieved (108 women). The principal features were mucosal ulcers (n = 129); fever (n = 93) followed by gastrointestinal (n = 81); skin features (n = 76); autoimmunity (n = 61), including thyroiditis (n = 25) and lupus (n = 16); and joint involvements (n = 54). Five patients had died at the time of publication. In 54 of 63 patients, CRP was significantly elevated during flares, with a median of 51 mg/l. The most commonly used treatment included corticosteroids and nonsteroidal anti-inflammatory drugs (n = 32), TNF blockers (n = 29), colchicine (n = 28), and methotrexate (n = 14). TNFAIP3 variants impacted the ovarian tumor domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, reported sex, and variant type significantly impacted phenotype. A better understanding of the wide A20 haploinsufficiency phenotype could facilitate the diagnosis process. Much remains to be elucidated about pathogenesis and treatment to improve outcome in patients with A20 haploinsufficiency.
Topics: Tumor Necrosis Factor alpha-Induced Protein 3; Humans; Haploinsufficiency; Female; Male; Hereditary Autoinflammatory Diseases
PubMed: 38128752
DOI: 10.1016/j.jid.2023.12.007 -
European Heart Journal Open Sep 2023Cardiac involvement is the foremost determinant of the clinical progression of amyloidosis. The diagnostic role of cardiac magnetic resonance (CMR) imaging in cardiac... (Review)
Review
Cardiac involvement is the foremost determinant of the clinical progression of amyloidosis. The diagnostic role of cardiac magnetic resonance (CMR) imaging in cardiac amyloidosis has been established, but the prognostic role of various right and left CMR tissue characterization and functional parameters, including global longitudinal strain (GLS), late gadolinium enhancement (LGE), and parametric mapping, is yet to be delineated. We searched EMBASE, PubMed, and MEDLINE for studies analysing the prognostic use of CMR imaging in patients with light chain amyloidosis or transthyretin amyloidosis cardiac amyloidosis. The primary endpoint was all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Nineteen studies with 2199 patients [66% males, median age 59.7 years, interquartile range (IQR) 58-67] were included. Median follow-up was 24 months (IQR 20-32), during which 40.8% of patients died. Both tissue characterization left heart parameters such as elevated extracellular volume [hazard ratio (HR) 3.95, 95% confidence interval (CI) 3.01-5.17], extension of left ventricular (LV) LGE (HR 2.69, 95% CI 2.07-3.49) elevated native T1 (HR 2.19, 95% CI 1.12-4.28), and functional parameters such as reduced LV GLS (HR 1.91, 95% CI 1.52-2.41) and reduced LV ejection fraction (EF; HR 1.20, 95% CI 1.17-1.23) were associated with increased all-cause mortality. Unlike the presence of right ventricular (RV) LGE (HR 3.40, 95% CI 0.51-22.54), parameters such as RV GLS (HR 2.08, 95% CI 1.6-2.69), RVEF (HR 1.13, 95% CI 1.05-1.22), and tricuspid annular systolic excursion (TAPSE) (HR 1.11, 95% CI 1.02-1.21) were also associated with mortality. In this large meta-analysis of patients with cardiac amyloidosis, CMR parameters assessing RV and LV function and tissue characterization were associated with an increased risk of mortality.
PubMed: 37840586
DOI: 10.1093/ehjopen/oead092 -
International Journal of Cardiology May 2024Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV).
METHODS
Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis.
RESULTS
A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m vs 127 ± 37 g/m, p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean).
CONCLUSION
Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis.
Topics: Adult; Humans; Female; Middle Aged; Aged; Adolescent; Male; Cardiomyopathies; Stroke Volume; Ventricular Function, Left; Magnetic Resonance Imaging; Myocardium; Amyloid Neuropathies, Familial; Disease Progression; Magnetic Resonance Imaging, Cine; Predictive Value of Tests; Contrast Media; Observational Studies as Topic
PubMed: 38382853
DOI: 10.1016/j.ijcard.2024.131892