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Hellenic Journal of Cardiology : HJC =... 2019Light-chain amyloidosis and transthyretin-related amyloidosis (wild-type and mutated) are three main types of systemic amyloidosis associated with a clinically relevant... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Light-chain amyloidosis and transthyretin-related amyloidosis (wild-type and mutated) are three main types of systemic amyloidosis associated with a clinically relevant cardiac involvement. In this study, we compared prognosis in patients with different categories of cardiac amyloidosis using meta-analysis and present a systematic review.
METHODS
A systematic literature search was performed through Jan 1, 2018, and two reviewers independently extracted data and assessed risk of bias. We extracted MACE and death endpoint events and hazard ratios from regression models and performed a meta-analysis of the multiple prognosis association studies.
RESULTS
We observed that there were significant MACE differences between patients diagnosed with transthyretin amyloidosis and light-chain amyloidosis (OR: 2.09; 95% CI: 1.06-4.12; P = 0.03), and the same is true in the sub-comparison between AL and mATTR or wtATTR (AL vs. mATTR: OR: 1.72; 95% CI: 1.06-2.82; P = 0.03; AL vs. wtATTR: OR: 1.48; 95% CI: 0.85-2.58; P = 0.17). However, no significant difference was observed between two transthyretin types (P = 0.17). Overall death rate evaluated showed that compared with transthyretin-related amyloidosis, light-chain type showed a significant difference (P < 0.05). The prognostic analysis showed that types of amyloidosis, LVEF, NYHA, restrictive filling pattern, E-wave deceleration time, E/E' ratio, and low QRS voltage were predictors of cardiac-related mortality.
CONCLUSION
Patients diagnosed with light-chain amyloidosis has a poor prognosis compared with transthyretin-related amyloidosis, while no difference was proved in prognostic analysis between wild-type and mutated TTR amyloidosis. Some clinical factors related to the death prognosis, such as the LVEF, restrictive filling pattern, E-wave deceleration time, and E/E' ratio are important prognostic factors.
Topics: Adult; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Cardiomyopathies; Case-Control Studies; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Prealbumin; Prognosis; Ventricular Function, Left
PubMed: 30742933
DOI: 10.1016/j.hjc.2019.01.015 -
International Journal of Heart Failure Jan 2024Atrial fibrillation is common in patients with cardiac amyloidosis. However, the optimal anticoagulation strategy to prevent thromboembolic events in patients with...
BACKGROUND AND OBJECTIVES
Atrial fibrillation is common in patients with cardiac amyloidosis. However, the optimal anticoagulation strategy to prevent thromboembolic events in patients with cardiac amyloidosis and atrial fibrillation is unknown. This systematic review and meta-analysis compares direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in patients with cardiac amyloidosis and atrial fibrillation.
METHODS
We performed a systematic literature review to identify clinical studies of anticoagulation therapies for patients with cardiac amyloidosis and atrial fibrillation. The primary outcomes of major bleeding and thrombotic events were reported using random effects risk ratios (RRs) with 95% confidence interval (CI).
RESULTS
Our search yielded 97 potential studies and evaluated 14 full-text articles based on title and abstract. We excluded 10 studies that were review articles or did not compare anticoagulation. We included 4 studies reporting on 1,579 patients. The pooled estimates are likely underpowered due to small sample sizes. There was no difference in bleeding events for patients with cardiac amyloidosis and atrial fibrillation treated with DOACs compared to VKAs with a RR of 0.64 (95% CI, 0.38-1.10; p=0.10). There were decreased thrombotic events for patients with cardiac amyloidosis and atrial fibrillation treated with DOACs compared to VKAs with a RR of 0.50 (95% CI, 0.32-0.79; p=0.003).
CONCLUSIONS
This systematic review and meta-analysis suggests that DOACs are as safe and effective as VKAs in patients with cardiac amyloidosis and atrial fibrillation. However, more data are needed to investigate clinical differences in anticoagulation therapy in this patient population.
PubMed: 38303916
DOI: 10.36628/ijhf.2023.0031 -
ESC Heart Failure Oct 2019The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.
METHODS AND RESULTS
MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias.
CONCLUSIONS
Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Diagnosis, Differential; Heart Diseases; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Prevalence; Radionuclide Imaging; Sensitivity and Specificity
PubMed: 31487121
DOI: 10.1002/ehf2.12511 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
BMC Neurology Feb 2021We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to compare neuropathic progression rate between hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and other peripheral neuropathies, including diabetic peripheral neuropathy (DPN) and Charcot-Marie-Tooth disease (CMT).
METHODS
Literature searches identified studies reporting neuropathic progression, measured by Neuropathy Impairment Score (NIS) or NIS-Lower Limbs (NIS-LL). Our study also included unpublished data from a clinical registry of patients who were diagnosed with different peripheral neuropathies and seen at the Oregon Health & Science University (OHSU) during 2016-2020. Meta-analysis and meta-regression models examined and compared annual progression rates, calculated from extracted data, between studies of ATTRv-PN and other peripheral neuropathies.
RESULTS
Data were synthesized from 15 studies in which NIS and/or NIS-LL total scores were assessed at least twice, with ≥12 weeks between assessments, among untreated patients with ATTRv-PN or other peripheral neuropathies. Meta-analysis models yielded that the annual progression rate in NIS total scores was significantly different from zero for studies in ATTRv-PN and CMT (11.77 and 1.41; both P < 0.001), but not DPN (- 1.96; P = 0.147). Meta-regression models showed significantly faster annual progression in studies in ATTRv-PN, which statistically exceeded that in other peripheral neuropathies by 12.45 points/year for NIS, and 6.96 for NIS-LL (both P < 0.001).
CONCLUSIONS
Peripheral nervous function deteriorates more rapidly in patients with ATTRv-PN than for other peripheral neuropathies. These findings may improve understanding of the natural history of neuropathy in ATTRv-PN, facilitate early diagnosis, and guide the development of assessment tools and therapies specifically targeting neuropathic progression in this debilitating disease.
Topics: Amyloid Neuropathies, Familial; Disease Progression; Female; Humans; Male; Middle Aged; Polyneuropathies; Registries
PubMed: 33579211
DOI: 10.1186/s12883-021-02094-y -
Heart Failure Reviews Jan 2021Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium,...
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium, resulting in cardiac structural and functional abnormalities and ultimately heart failure. Disease frequency is reportedly lower in women than men, but sex-related differences have not been well established. We conducted a systematic literature review (SLR), based on PRISMA-P guidelines and registered with PROSPERO, to assess whether the epidemiology and clinical presentation of ATTR-CM differ between women and men. MEDLINE, Embase, and Cochrane databases and selected conference proceedings were searched (August 16, 2019) to identify observational and clinical studies reporting sex-specific data for patients with wild-type or hereditary ATTR-CM. Of 193 publications satisfying final eligibility criteria, 69 studies were included in our pooled analysis. Among the 4669 patients with ATTR-CM analyzed, 791 (17%) were women, including 174 (9%), 366 (29%), and 251 (18%) in studies of wild-type, hereditary, and undefined ATTR-CM, respectively. Data available on disease characteristics were limited and very heterogeneous, but trends suggested some cardiac structural/functional differences, i.e., lower interventricular septal and posterior wall thickness and left ventricular (LV) end diastolic diameter, and higher LV ejection fractions, in women versus men across ATTR-CM subtypes. Because LV wall thickness > 12 mm is generally the suggested threshold for ATTR-CM diagnosis in both sexes, smaller cardiac anatomy in women with the disease may lead to underdiagnosis. Additional research and studies are needed to elucidate potential disparities between sexes in ATTR-CM frequency, clinical characteristics, and underlying biological mechanisms. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) database of the University of York (CRD42019146995).
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Female; Humans; Male; Prealbumin
PubMed: 32794090
DOI: 10.1007/s10741-020-10010-8 -
Clinical Autonomic Research : Official... Sep 2019Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic...
BACKGROUND
Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis.
METHODS
A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction.
RESULTS
Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment.
CONCLUSION
The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.
Topics: Amyloid Neuropathies, Familial; Autonomic Nervous System Diseases; Humans
PubMed: 31473866
DOI: 10.1007/s10286-019-00630-y -
ESC Heart Failure Apr 2024The prevalence of transthyretin-associated amyloidosis cardiomyopathy (ATTR-CM) has grown because of newer non-invasive diagnosis tools. Detecting the presence of... (Review)
Review
The prevalence of transthyretin-associated amyloidosis cardiomyopathy (ATTR-CM) has grown because of newer non-invasive diagnosis tools. Detecting the presence of extra-cardiac ATTR manifestations such as musculoskeletal pathologies considered 'red flags', when there is minimal or non-cardiac clinical involvement is primordial to carry out an early diagnosis. The aim of this systematic review is to examine the prevalence of musculoskeletal, ATTR-deposition-related co-morbidities in patients already diagnosed with ATTR-CM, specifically carpal tunnel syndrome, ruptured biceps tendon, spinal stenosis, and trigger finger. We performed a systematic review using PRISMA guidelines. Inclusion criteria were all studies in English and Spanish language and participants had to be patients diagnosed with ATTR-CM, by any diagnostic method, with the musculoskeletal co-morbidities subject of this review. The quality of the studies was based on the Risk of Bias Tool. This systematic review included 22 studies for final analysis. Carpal tunnel syndrome is reported in 21 studies, brachial biceps tendon rupture is reported in three, and spinal stenosis in eight studies. No articles that accomplished all the inclusion criteria for trigger finger were found. Regarding to the quality of the studies, all of them were categorized as being of high and moderate quality. The frequent association between ATTR-CM and carpal tunnel syndrome, ruptured biceps tendon, and lumbar spinal is confirmed, and the onset of these co-morbidities usually precedes the diagnosis of by years. This association defines them as red flags that should be search proactively due to the current treatment possibilities and the severity of the presentation of cardiac amyloidosis.
Topics: Humans; Prealbumin; Spinal Stenosis; Carpal Tunnel Syndrome; Trigger Finger Disorder; Amyloid Neuropathies, Familial; Cardiomyopathies; Morbidity
PubMed: 38130034
DOI: 10.1002/ehf2.14622 -
Journal of Cardiology Dec 2020The purpose of the current investigation was to evaluate the diagnostic accuracy of amyloid and F-18 sodium fluoride (NaF) positron emission tomography/computed... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The purpose of the current investigation was to evaluate the diagnostic accuracy of amyloid and F-18 sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) for the detection of cardiac amyloidosis (CA) using diagnostic accuracy test.
MATERIALS AND METHODS
The PubMed, Cochrane, and EMBASE database, from the earliest available date of indexing through February 29, 2020, were searched for results investigating the diagnostic accuracy of amyloid and F-18 NaF PET for the diagnosis of CA. We calculated the pooled sensitivities and specificities of included studies, calculated positive and negative likelihood ratios (LR+ and LR-), and obtained summary receiver operating characteristic (SROC) curves.
RESULTS
Across 13 studies with 14 results (90 patients), the pooled sensitivity of amyloid PET was 0.97 and a pooled specificity was 0.98. The pooled sensitivity of F-18 NaF PET was 0.63 and a pooled specificity was 1.00. The pooled sensitivity of combined amyloid and F-18 NaF PET was 0.88 and a pooled specificity was 0.98.
CONCLUSION
Amyloid PET has a high sensitivity and specificity for the detection of CA. However, F-18 NaF PET showed relatively low sensitivity with high specificity. At present, the literature regarding the use of amyloid and F-18 NaF PET for diagnosis of CA is still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of amyloid and F-18 NaF PET for detection of CA.
Topics: Amyloidosis; Fluorodeoxyglucose F18; Heart Diseases; Humans; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sodium Fluoride
PubMed: 32682627
DOI: 10.1016/j.jjcc.2020.07.003 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233