Amyloid-Journal of Protein Folding Disorders最新文献

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative disease leading to restrictive cardiomyopathy. We aimed to characterise exercise capacity in ATTRwt and to identify predictors of cardiopulmonary fitness, focusing on echocardiographic and clinical parameters.

Methods: We studied 110 ATTRwt patients from a prospective single-centre registry (2020-2024) by cardiopulmonary exercise testing (CPET). Besides CPET, all patients underwent comprehensive clinical assessment including follow-up for mortality. In 32 patients follow-up CPET after 1 year was available.

Results: In ATTRwt, reduced aerobic capacity (pVO2 16 [13-18] ml/kg/min), and ventilatory inefficiency (VE/VCO2 slope 35 [30-43]) were common. In the multivariable regression analysis, we identified TAPSE/sPAP ratio as predictive for pVO2 (p = 0.019) and ventilatory efficiency (p = 0.004), while left ventricular ejection fraction or measures of left ventricular hypertrophy were not predictive. Concordantly, TAPSE/sPAP ratio assessed at baseline predicted pVO2 at 1-year follow-up (p = 0.009). Furthermore, patients with a TAPSE/sPAP ratio below the median of 0.38 mm/mmHg presented a higher risk of all-cause death (p = 0.009).

Conclusion: In ATTRwt the TAPSE/sPAP ratio, a marker of right ventricular coupling, was an independent predictor of aerobic capacity assessed by CPET, at baseline and after 1 year, highlighting the importance of right ventricular assessment for risk stratification.

Background: Light-chain cardiac amyloidosis (AL-CA) is associated with structural and functional changes in the left atrium and left ventricle. This study aims to assess the value of the left atrioventricular coupling index (LACI) assessed by three-dimensional echocardiography (3DE) for predicting primary outcome in AL-CA.

Methods: Participants with biopsy-confirmed AL-CA from April 2022 to February 2024 were prospectively analysed. LACI, the ratio of left atrial volume min to left ventricular end-diastolic volumes, was calculated offline using EchoPAC 204. The primary outcome was defined as all-cause death.

Results: Sixty-seven biopsy-proven AL-CA patients were studied (age: 62.98 ± 10.20 years; 67% male). The median follow-up was 121 days (range: 7 ∼ 732 days). All-cause mortality occurred in 26 (39%) patients. Multivariate Cox regression revealed a significant association of LACI after adjusting for NT-pro BNP, troponin T, moderate tricuspid regurgitation, pericardial and pleural effusion (adjusted HR: 10.58, p = 0.008). Kaplan-Meier curves displayed prognostic differences based on median LACI (cut-off : 0.57, p = 0.002). The likelihood ratio χ2 test showed that LACI added predictive value to Mayo 2004, European 2015 modification of Mayo 2004, and Mayo 2012 models (All p < 0.001).

Conclusions: 3DE-based LACI is independently associated with all-cause mortality in AL-CA patients and augments prognostic value to traditional staging models.

Background: A high incidence of valvular involvement of amyloid in the setting of aortic stenosis (AS) has been reported. Amyloid derived from ApoAI (AApoAI) can form local amyloid deposits in the aortic valve. Although a high prevalence of concomitant severe AS and cardiac transthyretin-type amyloidosis (ATTR) has been reported, the prevalence of valvular involvement by ATTR and AApoAI is unclear.

Methods: Using immunostaining and mass spectrometry, we analysed amyloid proteins in 97 aortic valves removed for valve replacement due to AS at Kyoto Prefectural University of Medicine between 2014 and 2021. Clinical information was also reviewed.

Results: Amyloid deposits were found in 44 cases (45%), of which 30 cases (68%) involved ATTR and 33 cases (75%) AApoAI. Statistical analysis showed significantly lower age and E/e' among amyloid-positive cases compared with amyloid-negative cases and significantly lower brain natriuretic peptide, higher fractional shortening, and higher left ventricular ejection fraction among ATTR-positive cases compared with ATTR-negative cases. Seven recent patients underwent bone scintigraphy and ATTR cardiomyopathy was observed in only one case.

Conclusions: AS symptoms can manifest earlier in patients with amyloid or ATTR deposition in the aortic valve than in patients without such deposition, even though left ventricular function is preserved.

Introduction: Transthyretin (ATTR) amyloidosis is an ultimately fatal disease. While approved therapies slow disease progression, the cost of care can be significant for patients. The objective of this survey was to describe the factors associated with financial toxicity of ATTR amyloidosis and the economic burden of care and treatment.

Methods: The Amyloidosis Research Consortium (ARC) conducted an online survey in the United States for patients with ATTR amyloidosis and their caregivers. Financial toxicity was assessed using the COmprehensive Score for Financial Toxicity (COST). Multivariate linear regression was used to identify factors associated with financial toxicity controlling for key sociodemographic and patient characteristics.

Results: Of 452 respondents, 249 (55%) reported financial toxicity. Respondents who reported financial toxicity predominantly had ATTRv amyloidosis, were younger, non-white, had a household income <$100,000, had multiple sources of insurance, and were less frequently retired. Respondents reported using several ways to offset the cost of treatment.

Conclusions: Patients with ATTR amyloidosis experience significant financial distress that is comparable to patients with cancer, and as a result, many patients delay treatment or pay for treatment using savings and/or borrowing money. African American respondents (vs white) were significantly at risk.

Background: Accurate tissue typing in amyloidosis is essential to provide appropriate therapy for individual patients.

Objective: To get a real-life overview of typing strategies worldwide.

Methods: The International Society of Amyloidosis (ISA) performed an online questionnaire survey among ISA members. We prepared questionnaire sheets for referral institutions (Category 1; C1), institutions performing amyloid typing for internal requests only (C2), and institutions outsourcing amyloid typing to referral institutions (C3), respectively.

Results: Seventy-six institutions participated in this survey, including C1 (n = 33), C2 (n = 20) and C3 (n = 23) institutions. Multiple typing methods were available across the responding institutions, including immunohistochemistry (85% of C1/C2 institutions), immunofluorescence microscopy (43%), genetic analysis (77%) and mass spectrometric analysis (42%). Commercial antibodies were used worldwide for immunohistochemistry. C1 institutions in Europe and Asia also used various in-house antibodies. Ninety-three percent of institutions performed genetic analysis of TTR gene, followed by APOA1 (43%), FGA, GSN, LYZ (33%) and APOA2 (31%). Hierarchical referral flows of mass spectrometric analysis, immunohistochemistry and genetic analysis were observed regionally and internationally. Globalization and centralization of referral flows were more prominent for mass spectrometric analysis.

Conclusion: These data provide an assessment of the current state, enabling improvement in capabilities of amyloid typing worldwide and enhancing regional/international networks.

Introduction: Cardiac Amyloidosis (CA) is characterised by amyloid fibril deposits causing heart failure (HF). Lumbar spinal stenosis (LSS) is recognised as a potential red flag for CA, but the association remains underexplored in large-scale studies.

Methods: This nationwide registry-based cohort study in Denmark included subjects ≥60 years with a history of LSS surgery. LSS patients were matched 1:1 with controls by age, sex, ischaemic heart disease, chronic obstructive lung disease, chronic kidney disease, diabetes, and atrial fibrillation.

Results: A total of 44,548 LSS surgery patients and matched controls were included (median age 71.5 years, 56.2% women). The cumulative incidence of amyloidosis after 10 years was higher in the LSS group (0.16% vs. 0.08%, HR 2.29 [95% CI 1.46-3.60]) after adjustment for malignancy, hypertension, and liver disease. The cumulative incidence of HF after 10 years was 10.1% in LSS patients compared with 7.5% in controls (HR 1.28 [95% CI 1.22-1.35], p < 0.0001).

Conclusions: In this nationwide cohort study, LSS surgery was associated with a significantly higher risk of amyloidosis and HF. Prospective studies are warranted to explore the association further.

Aims: To evaluate the predictive value of the Columbia score in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

Methods: Observational study based in a prospective, multi-centre registry of patients with ATTR-CM recruited between January-2018 and December-2023 in 7 Spanish hospitals. The Baseline Columbia score was correlated by means of multivariable Cox's regression with study endpoints all-cause death and all-cause death or heart failure (HF) hospitalisation. Discriminative capacity was evaluated by means of Harrell's C statistics and area under 2-year time-dependent receiver-operator curves.

Results: We studied 374 patients with ATTR-CM. Columbia score was independently associated with increased risk of all-cause death (adjusted HR per 1 point = 1.30, 95% CI 1.17-1.45) and all-cause death or HF hospitalisation (adjusted HR per 1 point = 1.38, 95% 1.26-1.50). The score showed moderate discriminative capacity for all-cause death (Harrell's C = 0.653) and all-cause death or HF hospitalisation (Harrell's C = 0.697). The area under the 2-year time-dependent receiver-operator curve was 0.594 for all-cause death and 0.669 for all-cause death or HF hospitalisation. Columbia's score was adequately calibrated for both outcomes.

Conclusions: We studied the prognostic performance of the Columbia score in a Spanish prospective cohort of patients with ATTR-CM. The score showed adequate calibration and moderate discriminative capacity for predicting death and HF hospitalisations.