Amyloid-Journal of Protein Folding Disorders最新文献

Objectives: Tafamidis has demonstrated survival benefits in transthyretin amyloid cardiomyopathy (ATTR-CM), yet variability in therapeutic response underscores the need for reliable tools to predict outcomes. This study evaluates the prognostic utility of cardiopulmonary exercise testing (CPET) in this population.

Methods: This retrospective study included tafamidis treated wild-type (ATTRwt) CM patients who completed CPET. Univariable and multivariable Cox regression models were used to evaluate predictors of mortality and composite secondary endpoint (mortality and heart failure admissions).

Results: Total of 105 ATTRwt-CM patients were enrolled with median age of 80 years. During median follow-up of 2.1 years, 33 (31%) died and 67 (63.8%) had composite outcome of mortality and heart failure hospitalisations. Multivariable analysis showed VE/VCO₂ slope (HR 1.61 per SD, 95% CI: 1.13-2.30, p = 0.01), peak circulatory power [CP] (HR 0.43 per SD, 95% CI 0.21-0.89, p = 0.02), Mayo stage 3 (HR 5.34, 95% CI: 1.07-26.7, p = 0.04) were independent predictors of mortality. The VE/VCO₂ slope (HR 1.57 per SD, 95% CI 1.2, 2.05, p= <0.01), creatinine (HR 1.37 per SD, 95% CI 1.07, 1.76, p = 0.01) and Mayo stage 3 (HR 2.49, 95% CI 1.10, 5.66, p = 0.03) were independent predictors of composite outcome.

Conclusions: CPET provides prognostic insights for ATTRwt-CM patients in addition to known prognostic laboratory factors.

Background: Amyloid typing, particularly in monoclonal gammopathies of renal significance, can be technically challenging. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry Imaging (MALDI-MSI) has been proposed as a non-destructive method to detect and type amyloid deposits on a single tissue slide. This study aims to confirm this capability of MALDI-MSI in renal light chain amyloidosis (AL amyloidosis), irrespective of the fixative utilised, confronting results with other traditional and upcoming methods for amyloid detection.

Methodology: MALDI-MSI was applied to 15 renal biopsies diagnosed with AL amyloidosis. Results were compared with the routinely utilised methods of amyloid detection and typing, respectively, the pathologist's evaluation and immunofluorescence (IF) and additionally with a computational technique for amyloid detection, SPADA (Streamlined Pipeline for Amyloid Detection through Congo red fluorescence digital Analysis).

Results: MALDI-MSI demonstrated an agreement of 85.0% and 86.4% with SPADA and the pathologist in detecting glomerular deposits. It also showed complementary potential with SPADA, suggesting the possibility of combining all methodologies on a single tissue slide. Furthermore, MALDI-MSI showed a complete agreement with IF in amyloid typing.

Conclusion: This study confirmed the capability of MALDI-MSI to detect and type AL amyloidosis, assessing the possibility to integrate an additional computational method for amyloid detection on a single tissue slide.

Background: ATTR is a systemic disease, causing significant morbidity and mortality, manifesting with symptoms affecting both the heart and nervous system. This study employed the Composite Autonomic Symptom Scale 31 (COMPASS-31) to assess autonomic symptoms in relation to ATTR-CM subtypes and the impact of dysfunction on prognosis.

Methods: This study included contemporary ATTR-CM patients enrolled in an institutional registry from 7/21-6/24. Demographic information, patient-reported outcomes (COMPASS-31 and Kansas City Cardiomyopathy Questionnaire (KCCQ)), 6-min walk test, and clinical data (hospitalisations, mortality) were collected and compared between ATTR-CM sub-types (ATTRwt, ATTRv-Val122Ile, ATTRv-non Val122Ile).

Results: 240 ATTR-CM patients (81% ATTRwt, 11% Val-122Ile, 8% non-Val122Ile) were studied. Following adjustment for age, significant COMPASS-31 score differences were observed between ATTRwt and ATTRv-nonV122I variant patients. "High" COMPASS-31 scores (≥35.42) were associated with later Columbia stage, lower exercise tolerance, and poorer quality of life (QOL) (all p < 0.05). Time-to-event analysis demonstrated higher probability of cardiovascular hospitalisations (CVH) for patients with "High" COMPASS-31 scores (p < 0.01). These patients also had increased CVH risk (HR = 4.26 [95% CI: 1.85-9.83], p = 0.001) independent of age, sex, ATTR type, Columbia Stage and diabetes.

Conclusions: Among ATTR-CM patients, autonomic dysfunction assessed via COMPASS-31 questionnaire was associated with more advanced disease stage and QOL impairment, and independently predicted CVH risk.

The peripheral nervous system (PNS) is commonly affected in immunoglobulin light chain amyloid protein (AL) amyloidosis. PNS involvement and particularly small fiber neuropathy (SFN) is often clinically underestimated, requiring a standardized approach for comprehensive assessment. We prospectively evaluated the prevalence and clinical significance of SFN in 81 patients with newly diagnosed AL amyloidosis using clinical examination, nerve conduction studies (NCSs), quantitative sensory testing (QST) examination and distal-leg skin biopsy. Neuropathy was detected in 89% of patients and SFN in 65%. Combined small and large fiber neuropathy was seen in 48.1%, pure large fiber neuropathy in 20% and pure SNF in 10%. Older age was a significant risk factor for SFN (OR 1.06, 95% CI 1.01-1.12, p = .014); patients with SFN were also more likely to have soft tissue involvement (OR 7.1, 95% CI 1.5-33.4, p = .013). After a median follow-up of 37.5 months, SFN was associated with poorer overall survival (OS) and it emerged as an independent prognostic factor for early mortality (<12 months) in multivariate analysis (HR 4.3 95% CI 1.23-15.04, p = .023). Our study demonstrates the high prevalence and clinical significance of SFN as an adverse factor for survival and indicates the need for multiparametric neurological evaluation in patients with AL amyloidosis at diagnosis.