Amyloid Polyneuropathy Research Articles

The prevalence and prognostic impact of low voltage zone in patients with cardiomyopathy after catheter ablation for atrial fibrillation

Abstract Background The low voltage zone (LVZ) in left atrium (LA) was observed in 20-30% of patients undergoing catheter ablation of atrial fibrillation (AF). Furthermore, LVZ was associated with not only AF recurrence but also prognosis. However, the prevalence and prognostic impact of LVZ in patients diagnosed with cardiomyopathy remained unclear. Purpose In this study, we focused on the patients with cardiomyopathy after AF ablation and investigated the prevalence and prognostic impact of LVZ after AF ablation. Methods This study is a single-center retrospective observational study. We enrolled 125 patients diagnosed with cardiomyopathy. All patients underwent voltage mapping after pulmonary vein isolation. LVZ was defined as regions where bipolar peak-to-peak voltage was <0.5mV. We set 5 cm² as the cutoff of the presence of LVZ. The etiology of cardiomyopathy was divided into arrhythmia-induced cardiomyopathy (AICM) and non-AICM consisting of idiopathic dilated cardiomyopathy (iDCM), hypertrophic cardiomyopathy (HCM), ischemic cardiomyopathy (ICM), transthyretin amyloidosis wild type (ATTRwt) and others (1 Fabry disease, 1 cardiac sarcoidosis, 1 restrictive cardiomyopathy). AICM was defined as patient whose LVEF was recovered above 50% after maintenance of sinus rhythm. We investigated the proportion of LVZ by etiology, and the association between LVZ and the composite endpoint consisting of all cause death, heart failure hospitalization, ventricular assisting device implantation, ventricular arrhythmia and stroke. Results Out of 125 patients [age 68 (58-73), female 32 (25%), LVEF 34.0 (25-43)], 51 (41%) had LVZ. Sixty-four patients were AICM etiology (LVEF pre to post: 30.7±10.7% to 61.1±6.7% ) and 61 was Non-AICM etiology (LVEF: 40.7 ± 18.1 to 44.7±15.7, P=0.0062). The presence of LVZ was lower in AICM than in non-AICM group (20.3% vs. 62.3%, P<0.0001). The etiology of non-AICM was consisting of 26 iDCM, 18 HCM, 7 ICM, 7 ATRRwt and 3 other etiology. The prevalence of LVZ was lower in AICM than in non-AICM (20.3 vs. 62.3%, P<0.0001). Detail is shown in Figure 1. Next, the incidence of composite endpoint was higher in patients with LVZ than in those without (HR 4.6, 95%CI 2.1-10.0, P=0.0001) (Figure 2A). Among 4 groups stratified by AICM/non-AICM and with/without LVZ, there was significant difference in the incidence of the composite endpoint (Figure 2B, P<0.0001). After adjusted with age, gender, Non-AICM, LVZ, LVZ tended to have association with composite endpoint (2.21, 0.87-5.65, P=0.097) and Non-AICM showed strong association (5.58, 1.55-20.12, P=0.0086). LVZ was associated with HF hospitalization (4.35, 1.21-15.61, P=0.024). Conclusions The prevalence of LVZ was 60% in Non-AICM, while it was 20% in AICM. LVZ tended to be associated with poor prognosis of cardiomyopathy after AF ablation. LVZ was associated with HF hospitalization in patients with cardiomyopathy. LVZ might be the marker for poor prognosis in cardiomyopathy cohort.

Divergent Total Synthesis of Isoflavone Natural Products and Their Potential as Therapeutic Agents for TTR Amyloidosis.

We have achieved the divergent total synthesis of nine isoflavone natural products 1-9 starting from commercially available 2,4,6-trihydroxyacetophenone as a starting material. The isoflavone skeleton of 1-9 was constructed by the Suzuki-Miyaura coupling reaction as the key reaction. Investigation of the potential of 1-9 as therapeutic agents for transthyretin (TTR) amyloidosis revealed that millexatin F (3) showed the best efficacy in ex vivo competitive binding experiments and thioflavin-T fluorescence studies. Therefore, millexatin F (3) is promising as a seed compound for a novel TTR amyloidosis therapeutic agent.

Heart Failure with Preserved Ejection Fraction and Cardiac Amyloidosis in the Aging Heart.

Heart Failure with Preserved Ejection Fraction (HFpEF) is one of the most frequent causes of heart failure in the world's population (about 19-55%), and is commonly associated with a high rate of hospitalization (almost 70-80%) and with increased mortality (40-50% in a 5-year timeframe). The elderly are more often affected, with higher rates of hospitalizations than young people, and currently almost 70% of the population aged 65 years old has HFpEF. An increase in cardiomyocyte stiffness, thus resulting in diastolic dysfunction, increased filling pressures and heart failure with preserved ejection fraction are characteristics features of the disease. In addition, among the various causes of HFpEF, cardiac amyloidosis (CA) can provoke diastolic dysfunction and increased wall stiffness directly from intercellular deposition of insoluble proteic substances and their toxic activity. Totally, almost 30 different proteins are able to form deposits, but the most frequently involved are transthyretin and misfolded monoclonal immunoglobulin light chains, which bring to two clinical conditions called transthyretin amyloidosis (ATTR) and light-chain amyloidosis (AL). Although there has been increasing attention on ATTR-CA in recent years, the actual prevalence remains underestimated, especially in people of advanced age, as well as its real impact as a cause of HFpEF, and only data derived from autoptic exams are currently available. Moreover, CA itself often mimics HFpEF, and some conflicting data on the use of predictive scores are described in the literature. The close relationship between HFpEF and CA, especially in older population and the main pathophysiological mechanisms which bond these two conditions are described in this focused review. The need to screen red flags for ATTR-CA in elderly patients with HFpEF is urgently advised, because a prompt recognition of the disease can optimize the approach to the disease with an early therapeutic, life-saving choice.

CEPARM: Four decades of dedication to advancing Familial Amyloidotic Polyneuropathy research and patient care

This paper delves into the remarkable journey of theCentro de Paramiloidose Antônio Rodrigues de Mello (CEPARM),located at the Hospital Universitário Clementino Fraga Filho(HUCFF) of UFRJ, over the past four decades, from itsestablishment in 1984 to its emergence as a pioneering institution inthe so called field of Familial Amyloidotic Polyneuropathy (FAP).Founded in response to the urgent need for specialized researchand treatment of this rare genetic disorder prevalent amongindividuals of Portuguese descent mainly with expressivePolyneuropathy (Hereditary Transthyretin Amyloidosis withPolyneuropathy - hATTR-PN) or even Cardyomyopathy (HereditaryTransthyretin Amyloidosis with Cardyomyopathy hATTR-CM),CEPARM has played a crucial role in the evolution of this field.The paper offers a comprehensive overview of thecenter’s development, emphasizing its major achievements,research contributions, and advancements in patient care. Ithighlights CEPARM’s pivotal role in developing innovativetreatment protocols, including the introduction of livertransplantation for FAP and groundbreaking therapies such astafamidis, patisiran, inotersen, vutrisiran, and eplontersen.Additionally, the paper explores CEPARM’s efforts to enhancepatient quality of life through multidisciplinary care and supportprograms.By reflecting on the center’s historical milestones,leadership transitions, and ongoing initiatives, this paperunderscores CEPARM’s unwavering commitment to advancingscientific knowledge and improving patient outcomes mainly in therealm of hATTR-PN.

Neck triangle nerve enlargement in hereditary transthyretin amyloidosis correlates with changes in the autonomic, cardiac, and gastrointestinal systems.

Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear. We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5-C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis. We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6±5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross-sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy. Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv.

Transthyretin Cardiac Amyloidosis: Insights into Wild-Type Variants and Familial Amyloid Cardiomyopathy

Transthyretin (TTR) cardiac amyloidosis is a progressive condition characterized by amyloid fibril deposition in the heart, leading to heart failure. This review focuses on insights into wild-type (ATTRwt) and familial (ATTRm) variants of TTR amyloidosis. The pathophysiology involves TTR tetramer destabilization, monomer misfolding, and amyloid fibril formation. Therapeutic advances, including TTR stabilizers like tafamidis and Diflunisal, and gene-silencing agents such as patisiran and inotersen, show promise in managing the disease. Despite these advancements, early diagnosis remains challenging, and side effects of current therapies necessitate the development of safer, more effective treatments. Future research should focus on novel therapies, improved diagnostic methods, and personalized treatment strategies to enhance patient outcomes. This review underscores the importance of continued innovation and collaboration in tackling TTR cardiac amyloidosis.

Hereditary Transthyretin-Related Amyloidosis Ongoing Observational Study: A Baseline Report of the First 3167 Participants.

Background: Hereditary transthyretin-related amyloidosis is a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene (hATTR amyloidosis). Objective: The current study describes the demographic, clinical, and genetic characteristics of patients with suspected hATTR amyloidosis. Methods: This study is part of the "Hereditary transthyretin-related amyloidosis and longitudinal monitoring of TTR-positive patients" (TRAMmoniTTR) study. This study included 3167 participants, along with their clinical details. Principal component (PC) analysis was used to analyze their clinical symptomatology. Next-generation sequencing of the TTR gene was performed and genotype-phenotype relationships were investigated. We compared the demographic and clinical characteristics using the principal components (PCs) and also compared participants with and without the TTR pathogenic variants. Results: We identified five main clinical phenotypes out of 22 single symptoms that explained 49% of the variation. The first two PCs referred to polyneuropathy and cardiomyopathy. We found significant differences between gender and PC-polyneuropathy and PC-cardiomyopathy, with male over-representation in the higher quantiles of PC-polyneuropathy and male under-representation in the lowest quantiles of PC-cardiomyopathy. We identified 92 participants with hATTR (3%), exhibiting 17 unique heterozygous TTR variants. The p.Val50Met variant was the most frequent. Furthermore, 503 participants (20%) were identified with ATTR and no relevant TTR variants (ATTRwt). We detected significant differences between the ATTRwt and hATTR groups, with male gender predominance in only the ATTRwt group and a positive family history of polyneuropathy and/or cardiomyopathy among the hATTR participants. Conclusions: The current clinical and genetic characterization of this cohort serves as a foundation for further longitudinal monitoring and assessment.

TTR associated leptomeningeal amyloidosis in a Sri Lankan patient

ObjectivesThis case report aims to contribute to the expanding genotypic-phenotypic spectrum of TTR associated leptomeningeal amyloidosis. MethodsNeuroimaging and targeted TTR Sanger sequencing were performed on a 52-year-old female presenting with cognitive and motor symptoms. ResultsThe proband, a Sri Lankan woman, presented with a gradually progressive cognitive decline, followed by a rapid deterioration in motor function and level of consciousness. She had a significant family history of an undiagnosed neurological disorder, characterized by cognitive impairment and early death occurring in the fifth decade of life. Analysis of cerebrospinal fluid (CSF) demonstrated elevated protein levels. CT scan of the brain showed extensive leptomeningeal calcifications and hydrocephalus, and gadolinium enhanced magnetic resonance imaging (MRI) demonstrated extensive leptomeningeal enhancement in the brain and spinal cord.Genetic analysis revealed c.113 A > G, p.D38G mutation in TTR, a rare mutation with characteristic clinic-radiological central nervous system features. DiscussionLeptomeningeal amyloidosis represents the least common subtype of familial transthyretin amyloidosis, which is a life-threatening condition. Among the over 150 identified mutations, few are specifically associated with central nervous system disease. The genetic spectrum and clinical phenotypes including neuroimaging findings continue to expand. It is important to maintain a high index of suspicion for leptomeningeal amyloidosis, particularly when the presentation is not acute or when there are relapsing-remitting symptoms. Consideration of family history and early genetic testing are essential to facilitate appropriate treatment and genetic counselling.

Hereditary Transthyretin Amyloidosis Polyneuropathy.

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., 99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

Diagnostic delay in patients with sporadic hereditary transthyretin-mediated amyloidosis.

Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis) is a rare progressively incapacitating condition with a wide range of genotype/phenotype presentations. It is frequently diagnosed late in its course, particularly in sporadic cases. Analysing predictors of diagnostic delay in this subpopulation should be, therefore, a priority. 109 apparently sporadic ATTRv amyloidosis patients followed in a reference centre in Hospital de Santa Maria (ULS Santa Maria-CAML), in Lisbon, were studied. Time from symptom onset to diagnosis, age, sex, municipality of origin and initial symptoms were obtained. Diagnostic delay was compared between different decades with a Kruskal-Wallis test, and its predictors were evaluated in a univariate model followed by a binary logistic regression analysis to calculate the adjusted odds ratio. The median diagnostic delay was 1262days. There was a non-significant difference in diagnostic delay between the 80s, 90s, 2000s and 2010s decades. There was a non-significant trend for a longer diagnostic delay in woman and in patients having no neurologic symptoms at onset. There is an important diagnostic delay in sporadic cases of ATTRv amyloidosis. Awareness should be spread among clinicians regarding the various manifestations of this disease, stressing the importance of family history and epidemiological data.

Transthyretin amyloidosis in patients with spinal stenosis who underwent spinal surgery: a systematic review and meta-analysis.

Accumulation of transthyretin amyloids (ATTR) is detected in ligamentum flavum in about 1/3 of patients underwent surgery for spinal stenosis. However, the significance of this finding is not known. The aim of this systematic review and meta-analysis is to analyze the incidence and importance of ATTR in patients with spinal stenosis who underwent spinal surgery. The primary outcome measure was incidence of ATTR in patients with spinal stenosis. English language observational studies published within 10 years period were searched in Pubmed and Taylor and Francis databases. Nine articles were included in the systematic review. The incidence of positive ATTR among patients who underwent lumbar spinal surgery was 48% (95%CI 38-58%). ATTR deposits were found in the lumbar region the most frequently. Seven studies showed that patients with positive ATTR were older than those with negative. Five studies investigated and found a significant relationship between the ligamentum flavum thickness and positive ATTR. Five studies investigated cardiac involvement among patients with positive ATTR. ATTR deposits are frequently found in older patients with spinal stenosis, especially in the lumbar region. The presence of ATTR deposits is related to ligamentum flavum thickness.

Clinical outcomes for 2788 patients with transthyretin amyloidosis: Tafamidis meglumine early access program in France

BackgroundEarly access experience in France with tafamidis meglumine, a selective transthyretin stabilizer for transthyretin-related amyloidosis cardiomyopathy (ATTR-CM), following transthyretin-related amyloidosis (ATTR) polyneuropathy approval and positive ATTR-ACT study results. AimTo describe the characteristics and clinical outcomes for patients in the French ATTR-CM tafamidis meglumine early access programme (28 Nov 2018 to 01 Jun 2021). MethodsPatients with confirmed ATTR-CM received tafamidis meglumine 20mg/day or 80mg/day. Demographic and clinical data were collected prospectively until patients discontinued treatment or died, or the programme ended. ResultsOverall, 222 physicians from 126 centres enrolled 2788 patients. The median age was 82years, 81.6% were male and New York Heart Association severity was class I for 12.8%, class II for 60.1% and class III for 27.0%. Overall, 1943 (74.6%) had genetic testing, and the results were available at tafamidis start for 1208 (62.2%) patients: 995 (82.4%) had wild-type ATTR and 213 (17.6%) had hereditary ATTR. Most patients started treatment≤12months after diagnosis (88.3%): 2268 (81.3%) at 20mg/day, with 401 (17.7%) increasing to 80mg/day. Median follow-up duration was 11.8months. New York Heart Association class improved or remained stable for 1299 (77.6%), whereas 376 (22.4%) worsened between inclusion and last follow-up. Among patients initiated at 80mg, 297 (81.1%) improved or remained stable and 69 (18.9%) worsened. New York Heart Association class progression did not vary with age. The 18-month survival rates were 89.8% (95% confidence interval: 87.0–92.0) among patients aged<80years, and 86.5% (95% confidence interval: 83.9–88.7) among those aged≥80years. ConclusionsEarly tafamidis meglumine access was given to 2788 patients with ATTR-CM. New York Heart Association class progression and survival were consistent with previously published data.

Neuroprotective effect against amyloidogenic transthyretin aggregates - Induced cytotoxicity on human neuroblastoma cell by phenolic-rich Centella asiatica extract

Transthyretin (ATTR) amyloidosis is a progressive and life-threatening neurodegenerative disease caused by aggregation of the plasma transport protein, transthyretin, for which treatment is rare and cure unavailable. Centella asiatica is a small edible herb with a long history of neurological application in ethnomedicine. This work investigated whether hydrophilic extract of C. asiatica (CAB) could suppress the toxic effects of transthyretin amyloid aggregate (TTRa) in cell model derived from the same in vivo target. TTRa was prepared via thermal-induced aggregation. Chemical cross-linking and Tricine-SDS-PAGE, Thioflavin-T fluorescence, and TEM analyses confirmed that TTRa matched the profile of TTRL55P nonfibrillar amyloid aggregates. PrestoBlue cell viability assay revealed that exposure of IMR-32 human neuroblastoma cells to TTRa (2–8 μM) resulted in significant cytotoxicity. Conversely, exposure of IMR-32 cells to CAB did not adversely affect their viability. In addition, when IMR-32 cells were co-treated with TTRa and varied concentrations of CAB, the toxic effect of TTRa was significantly (p < 0.01) inhibited dose-dependently. The extract was found to possess potent radical scavenging effects, and quantitative RP-HPLC analysis showed that asiaticoside and phenolics were its main components. The cytoprotective effect against TTRa, antioxidant property, and good safety profile collectively suggest that CAB could be applied in the development of nutraceuticals or therapeutics against transthyretin amyloidosis.

“A hot topic”: TTR amyloidosis gets its moment to shine at ESC 2024

n transthyretin amyloidosis (ATTR), the liver produces an abnormal transthyretin (TTR) protein, which aggregates into amyloid fibrils that accumulate in peripheral nerves and the heart. Over time, this can lead to progressive cardiomyopathy (ATTR-CM), heart failure (HF), and premature mortality. At the recent meeting of the ESC there was much excitement and enthusiasm about ATTR-CM, largely inspired by the HELIOS-B trial of vutrisiran, an RNA interference (RNAi) agent that, if approved, would become only the second medication indicated for ATTR-CM. This report reviews the most relevant insights from the meeting into the diagnosis and management of ATTR-CM, with expert commentary on their relevance and implications for Canadian clinicians.

Transthyretin amyloidosis prevalence and characteristics in Korean patients with heart failure with preserved or mildly reduced ejection fractions

The diagnosis and awareness of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in heart failure with left ventricular ejection fraction (LVEF) > 40% remains under-recognized. This study aimed to investigate the prevalence and characteristics of ATTR-CM in patients with heart failure with LVEF > 40%. Patients with LVEF > 40% and maximal left ventricular wall thickness (MWT) > 10 mm who underwent bone scintigraphy were retrospectively investigated. Patients with a definite cause of heart failure were excluded. ATTR-CM was diagnosed when grade 2 or 3 myocardial uptake was observed on scintigraphy. Among 97 patients (male, 62.5%; median age, 69 years), 13 (13.4%) were diagnosed with ATTR-CM (wild type, 69.2%; hereditary type, 30.8%). Age or biomarker levels did not differ significantly; however, all patients with ATTR-CM were male. The ATTR-CM group had a significantly higher prevalence of polyneuropathy or carpal tunnel syndrome than the non-ATTR-CM group, accompanied by a longer PR interval, thicker MWT, larger left atrial volume index, and higher E/e′. Accordingly, ATTR was present in a substantial number, particularly among men. Clinicians should suspect ATTR when a male patient exhibits neurologic symptoms, diastolic dysfunction, and a long PR interval.

Aspects cliniques des amyloses systémiques en 2024

The three most common varieties of systemic amyloidosis are transthyretin amyloidosis (ATTR), immunoglobulin amyloidosis (AL) and inflammatory amyloidosis (AA). There are two forms of transthyretin amyloidosis: the wild type, the most common, represents approximately 15% of heart diseases and the genetic, or "mutated" form, which is a rare disease and manifests mainly by peripheral neuropathy and heart disease. Major therapeutic advances have been made in recent years thanks to molecules that stabilize transthyretin and/or prevent its translation by destroying messenger RNA. Immunoglobulin amyloidosis (AL) is a hematological disease whose severity is due to the toxicity of immunoglobulin light chains forming amyloid deposits that are toxic to tissues, particularly the heart and kidneys. Treatments for immunoglobulin amyloidosis are increasingly effective, and target the plasma cell, leading to an overall improvement in the prognosis, with cardiac involvement being the most worrying condition. Inflammatory amyloidosis (AA) complicates chronic inflammatory diseases less often due to the effectiveness of anti-inflammatory biotherapies in inflammatory rheumatism, chronic inflammatory bowel diseases and genetic auto-inflammatory diseases. The causes of inflammatory amyloidosis are now more diverse with an increase in cases of unknown cause associated or not with obesity.

A multicenter study of clinical predictors of positive pyrophosphate scintigraphy findings in the diagnosis of transthyretin amyloidosis

BackgroundThe prevalence of wild-type transthyretin (ATTR) amyloidosis is increasing with advancements in diagnostic techniques and growing awareness of the disease worldwide. 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy exhibits high performance in diagnosing ATTR cardiac amyloidosis. This study aimed to validate the characteristics of patients with positive 99mTc-PYP scintigraphy results in a multicenter setting to provide more accurate case selection criteria. Methods and resultsIn total, 180 patients with suspected ATTR amyloidosis underwent 99mTc-PYP scintigraphy in participating institutions in Japan between January 2018 and July 2022. Of 135 patients included in the analysis, 62 were 99mTc-PYP-positive. Logistic regression analysis was performed, and the following five factors were adopted to create a scoring system, with each weighted according to its odds ratio value; 1 point was scored for the absence of hypertension, existence of peripheral entrapment neuropathy (carpal tunnel syndrome or spinal canal stenosis), conduction disturbance (the presence of QRS complex ≥120 ms, first-degree atrioventricular block, higher degree of atrioventricular block, or presence of pacemaker implantation), and left ventricular hypertrophy and 2 points for troponin I/T ≥ 0.06 ng/mL. 99mTc-PYP scintigraphy positivity rate in the 0-point group was 0 %, whereas that in the 6-point group was 100 %. The area under the curve of the criteria was 0.820 (95 % confidence interval, 0.752–0.888; P < 0.001). ConclusionsThe combination of clinical information, which is easily available in local clinics, can provide accurate pretest prediction of positive 99mTc-PYP scintigraphy results. This will help clinicians to make an early diagnosis of ATTR amyloidosis.

ATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity.

Amyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form by the liver, but also by retinal epithelium and choroid plexus. The deposition of these fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryoelectron microscopy (cryo-EM), we investigated fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found consistent fibril structures from both tissues, similar to cardiac fibrils previously described, but different from vitreous humor fibrils of the same genotype. Our findings, along with previous ATTR fibrils structural studies, suggest a uniform fibrillar architecture across different tissues when transthyretin originates from the liver. This study advances our understanding of how deposition and production sites influence fibril structure in ATTRv-V30M amyloidosis.

Diagnosing AL and ATTR Amyloid Cardiomyopathy: A Multidisciplinary Approach.

Amyloidosis with cardiac involvement is a fatal disease leading to progressive heart failure. The most common forms of amyloidosis with cardiac involvement are light chain (AL) and transthyretin (ATTR) amyloidosis. To allow effective specific treatment for both forms, precise and early diagnosis is important. This review focuses on diagnostic approaches for AL and ATTR amyloidosis with cardiac involvement, including different strategies, the role of imaging and biomarkers and possible pitfalls.

L’amylose – point de vue du pathologiste

Despite the advent of scintigraphic diagnosis of transthyretin amyloidosis, the role of pathologists remains central for the diagnosis and typing of amyloidosis. The anatomo-pathological diagnosis and typing of amyloidosis are hindered by pitfalls that should be known, linked to the Congo red staining (technical implementation and interpretation) and the difficulties of immunohistochemistry. The use of expert centers is recommended for difficult cases and when the type cannot be confirmed.