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Background Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype.

Abstract Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. Objective: To evaluate the prevalence of RTA in individuals with ATTRv. Methods: We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 +) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. Results: We selected 49 individuals with a mean age of 40 (35.5–56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

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Purpose of Review: Cardiac amyloidosis is a condition marked by the misfolding of precursor proteins into insoluble amyloid fibrils, leading to restrictive cardiomyopathy and heart failure symptoms. This review discusses advancements in nuclear imaging techniques that enhance the diagnosis and guide the management of cardiac amyloidosis, addressing the critical need for early and accurate detection in clinical practice., Recent Findings: Recent studies and guidelines emphasizes the pivotal role of nuclear imaging techniques in diagnosing cardiac amyloidosis. Cardiac scintigraphy, using bone-avid tracers like 99mTc-PYP, 99mTc-DPD, and 99mTc-HMDP, is instrumental in distinguishing between transthyretin amyloidosis and light chain amyloidosis. PET, with tracers such as 11C-Pittsburgh Compound B (11C-PiB) and 18F-Florbetapir, offers significant potential in measuring amyloid burden and monitoring disease progression, providing detailed insights into the myocardial involvement., Summary: The advancements in nuclear imaging techniques significantly impact the management of cardiac amyloidosis. These methods allow for a more accurate diagnosis, detailed assessment of disease extent, and better differentiation between amyloidosis types, which are crucial for tailoring treatment approaches. The integration of these techniques into clinical practice is essential for improving patient outcomes and advancing research in cardiac amyloidosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

ABSTRACT Background: Hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy is a rare, inherited, multisystem, and often fatal disease caused by a variant in transthyretin (TTR) gene. Baseline characteristics of patients, especially anthropometric data, are scarce in the literature, and they are relevant to define effective treatment strategies. Objective: This study aimed to describe baseline demographic, anthropometric, and disease characteristics in a cohort of patients from a reference center in Brazil. Methods: Symptomatic patients not previously included in clinical trials and eligible for treatment were enrolled. Ethnicity, state of residence, age, sex, weight, height, body mass index (BMI), TTR variant, and Polyneuropathy Disability Score (PND) at diagnosis were analyzed. Results: Among the 108 patients enrolled, 58.33% were male, 60.19% were Caucasian, and 83.33% lived in the Southeast region. Mean age was 51.61 (±16.37) years, mean weight was 65.76 (±15.16) kg, mean height was 168.33 (±10.26) cm, and mean BMI was 23.11 (±4.45) kg/m2. The most prevalent variant was V30M (86.11%). Patients with PND score 0 presenting autonomic neuropathy were 14.81%. Patients with PND score I-II and III-IV were 52.78 and 32.41%, respectively. Mean weight and BMI were significantly lower in patients with sensory-motor manifestations. Conclusions: This is the largest cohort of patients in Brazil for whom anthropometric characteristics have been described. Baseline demographic, anthropometric, and disease data indicate that delay in diagnosis of hATTR amyloidosis with polyneuropathy is still a problem and that efforts must be made to expedite diagnosis and maximize opportunities for new disease-modifying treatments.

Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention., (© 2024. The Author(s).)

Pathological cardiac hypertrophy is a complex process that often leads to heart failure. Label-free proteomics has emerged as an important platform to reveal protein variations and to elucidate the mechanisms of cardiac hypertrophy. Endomyocardial biopsy is a minimally invasive technique for sampling cardiac tissue, but it yields only limited amounts of an ethically permissible specimen. After regular pathological examination, the remaining trace samples pose significant challenges for effective protein extraction and mass spectrometry analysis. Herein, we developed trace cardiac tissue proteomics based on the anchor-nanoparticles (TCPA) method. We identified an average of 6666 protein groups using ∼50 μg of myocardial interventricular septum samples by TCPA. We then applied TCPA to acquire proteomics from patients' cardiac samples both diagnosed as hypertrophic hearts and myocarditis controls and identified significant alterations in pathways such as regulation of actin cytoskeleton, oxidative phosphorylation, and cGMP-PKG signaling pathway. Moreover, we found multiple lipid metabolic pathways to be dysregulated in transthyretin cardiac amyloidosis compared to other types of cardiac hypertrophy. TCPA offers a new technique for studying pathological cardiac hypertrophy and can serve as a platform toolbox for proteomic research in other cardiac diseases.

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 2 vs 127 ± 37 g/m 2 , 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 2  = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I 2  = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I 2  = 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2024. Published by Elsevier B.V.)