-
Journal of Comparative Effectiveness... Jun 2024The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy... (Review)
Review
The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.
PubMed: 38869839
DOI: 10.57264/cer-2023-0158 -
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 -
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 -
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 -
Journal of Cutaneous Pathology May 2024Macular amyloidosis (MA) is a primary localized cutaneous amyloidosis, characterized by amyloid deposition in the papillary dermis. The clinical presentation includes... (Review)
Review
Macular amyloidosis (MA) is a primary localized cutaneous amyloidosis, characterized by amyloid deposition in the papillary dermis. The clinical presentation includes pruritic hyperpigmented macules and patches with a reticulated or rippled pattern, primarily found on the upper back and extremities. Biopsy is an essential diagnostic tool for confirming MA. This systematic review focused on the biopsy outcomes in patients diagnosed with MA.
Topics: Humans; Amyloidosis; Skin; Amyloidosis, Familial; Biopsy; Skin Diseases; Skin Diseases, Genetic
PubMed: 38328942
DOI: 10.1111/cup.14592 -
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 -
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 -
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 -
British Journal of Haematology Jul 2023Systemic AL amyloidosis is an incurable condition with various presentations and may cause multiple complications related to organ involvement. As survival has improved,...
Systemic AL amyloidosis is an incurable condition with various presentations and may cause multiple complications related to organ involvement. As survival has improved, disease and therapy-related quality of life (QoL) is becoming an increasingly important treatment endpoint. We review the literature summarising the utilised QoL questionnaires (QLQs) and assess their validity according to COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) standards. Thirteen retrospective observational studies and thirty-two prospective clinical trials were analysed. Most QLQs are generic or only validated in populations with distinct complications of the disease. None meet 'strong evidence' for validation in this context. There is a need to develop a disease-specific QLQ, which could inform treatment choices and facilitate the approval of novel therapies.
Topics: Humans; Quality of Life; Immunoglobulin Light-chain Amyloidosis; Prospective Studies; Retrospective Studies; Patient Reported Outcome Measures; Surveys and Questionnaires
PubMed: 37194132
DOI: 10.1111/bjh.18860 -
European Archives of... Jul 2023The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery. (Review)
Review
PURPOSE
The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery.
METHODS
A systematic review searching PubMed and EMBASE was performed. A qualitative synthesis of data regarding the surgical management of LA and a quantitative analysis of the recurrence rate after surgery was conducted.
RESULTS
This systematic review included 14 retrospective studies, one of whom is retrospective controlled. A total of 515 subjects were included, the mean age ranged from 43.3 to 58 years with a male-to-female ratio of 1:1.3. All cases had a localized laryngeal amyloidosis. The supraglottic region was the most affected laryngeal site and multiple sites were commonly involved. Surgical treatment consists of endoscopic excision using laser, cold or powered instruments. Open surgery is required for severe primary case or revision surgery. Surgical complications such as granulomatosis scar tissue formation, tracheostomy, laryngotracheal stenosis, pneumothorax and concomitant malignancy were developed in 17.5% of patients. The time onset to diagnosis varied from 1 months to 15 years and the duration of follow-up from 3 months to 25 years. The rate of recurrence was 28.4% (95% CI 24.5-32.6) and the timing of recurrences ranged from 3 months to 10 years.
CONCLUSION
The recurrence rate after primary surgery for laryngeal amyloidosis is high. A tailored surgical treatment based on the disease extension and a long-term follow up are recommended.
Topics: Humans; Male; Female; Adult; Middle Aged; Retrospective Studies; Laryngeal Diseases; Larynx; Laryngostenosis; Amyloidosis
PubMed: 36790723
DOI: 10.1007/s00405-023-07881-6