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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 -
Journal of Neurology Mar 2022To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke...
Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.
OBJECTIVE
To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).
METHODS
We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.
RESULTS
We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31).
CONCLUSIONS
Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.
Topics: Aged; Brain Ischemia; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Female; Humans; Ischemic Stroke; Magnetic Resonance Imaging; Male; Stroke; Subarachnoid Hemorrhage
PubMed: 34272978
DOI: 10.1007/s00415-021-10706-3 -
European Journal of Clinical... Dec 2021Transthyretin-related cardiac amyloidosis (TTR-CA) is thought to be particularly common in specific at-risk conditions, including aortic stenosis (AS), heart failure...
BACKGROUND
Transthyretin-related cardiac amyloidosis (TTR-CA) is thought to be particularly common in specific at-risk conditions, including aortic stenosis (AS), heart failure with preserved ejection fraction (HFpEF), carpal tunnel syndrome (CTS) and left ventricular hypertrophy or hypertrophic cardiomyopathy (LVH/HCM).
METHODS
We performed a systematic revision of the literature, including only prospective studies performing TTR-CA screening with bone scintigraphy in the above-mentioned conditions. Assessment of other forms of CA was also evaluated. For selected items, pooled estimates of proportions or means were obtained using a meta-analytic approach.
RESULTS
Nine studies (3 AS, 2 HFpEF, 2 CTS and 2 LVH/HCM) accounting for 1375 screened patients were included. One hundred fifty-six (11.3%) TTR-CA patients were identified (11.4% in AS, 14.8% in HFpEF, 2.6% in CTS and 12.9% in LVH/HCM). Exclusion of other forms of CA and use of genetic testing was overall puzzled. Age at TTR-CA recognition was significantly older than that of the overall screened population in AS (86 vs. 83 years, p = .04), LVH/HCM (75 vs. 63, p < .01) and CTS (82 vs. 71), but not in HFpEF (83 vs. 79, p = .35). In terms of comorbidities, hypertension, diabetes and atrial fibrillation were highly prevalent in TTR-CA-diagnosed patients, as well as in those with an implanted pacemaker.
CONCLUSIONS
Screening with bone scintigraphy found an 11-15% TTR-CA prevalence in patients with AS, HFpEF and LVH/HCM. AS and HFpEF patients were typically older than 80 years at TTR-CA diagnosis and frequently accompanied by comorbidities. Several studies showed limitations in the application of recommended TTR-CA diagnostic algorithm, which should be addressed in future prospective studies.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Aortic Valve Stenosis; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Carpal Tunnel Syndrome; Heart Failure; Humans; Hypertrophy, Left Ventricular; Radionuclide Imaging; Stroke Volume
PubMed: 34390490
DOI: 10.1111/eci.13665 -
Neurology Dec 2019To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA).
METHODS
This was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used.
RESULTS
We included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%-41%; 87.94%; < 0.001): focal cSS prevalence was 14% (95% CI 12%-16%; 6.75%; = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%-26%; 90.39%; < 0.001). During a mean follow-up of 3.1 years (range 1-4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%-9.8% per year; 83%; < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%-6.1%; 70%; = 0.018) for patients without cSS, 11.1% (95% CI 7%-15.2%; 56.8%; = 0.074) for cSS presence, 9.1% (95% CI 5.5%-12.8%; 0%; = 0.994) for focal cSS, and 12.5% (95% CI 5.3%-19.7%; 73.2%; = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19-3.85; < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31-2.41; = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91-6.30; < 0.0001).
CONCLUSION
In patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.
Topics: Aged; Brain Diseases; Cerebral Amyloid Angiopathy; Cerebral Cortex; Cerebral Hemorrhage; Female; Hemosiderosis; Humans; Male; Middle Aged; Prevalence; Risk Factors
PubMed: 31732564
DOI: 10.1212/WNL.0000000000008590 -
EJHaem Aug 2023Long-term follow-up of multiple myeloma (MM) clinical trials are needed to assess long-term outcomes. We aimed to investigate the length of follow-up of all phase III MM...
Long-term follow-up of multiple myeloma (MM) clinical trials are needed to assess long-term outcomes. We aimed to investigate the length of follow-up of all phase III MM clinical trials. Median follow-up duration of clinical trials of newly diagnosed MM was longer when compared to relapsed/refractory MM clinical trials (42.7 vs. 20.5 months, respectively). The follow-up duration of phase III clinical trials in MM is relatively short when compared to the improved outcomes in the current era. Efforts should be made to facilitate long-term clinical trials follow-up and/or publication of results of updated results.
PubMed: 37601879
DOI: 10.1002/jha2.680 -
European Journal of Nuclear Medicine... May 2024
PubMed: 37606860
DOI: 10.1007/s00259-023-06408-9