Search Results (164)

Transthyretin amyloidosis (ATTR) is a rare disease caused by misfolded proteins, amyloids, that are deposited in various organs and tissues, typically the heart and/or nerves, causing the development of cardiomyopathy (CM) and polyneuropathy (PN). Although this may be an incurable disease, there are various treatments that are currently available for patients with ATTR, including transthyretin (TTR) silencers such as inotersen and patisiran. The silencers help slow down the progression of disease and improve the quality of life of patients with ATTR by alleviating the cardiac and neurological symptoms that patients present. The purpose of this study was to compare the cardiac findings observed in the ⁹⁹Tc-PYP scintigraphy (PYP scan) parameters of patients with a mixed phenotype before and after treatment with inotersen or patisiran. This study included ten patients from the amyloidosis clinic at the University Health Network. All of the patients (average age: 63.80 ± 11.70; 60.0% males, 40.0% females) received inotersen or patisiran as their treatment. These patients underwent a PYP scan before and after treatment to observe any improvements in terms of their CM post-treatment. Nine (90.0%) patients showed an improvement with their CM, as they showed a decrease in their heart-to-contralateral lung (H/CL) ratio and/or pyrophosphate (PYP) grade based on their results from the PYP scan post-treatment with a TTR silencer. Only one patient (10.0%) had worsening results, as their H/CL ratio and PYP grade increased post-treatment in comparison to the PYP scan results pre-treatment. Patients with ATTR who have a mixed phenotype should undergo a PYP scan before and after treatment with a TTR silencer. By undergoing these scans, the effectiveness of this treatment could be determined by observing any improvements in the signs of CM. A decrease in the H/CL ratio and/or the PYP grade would indicate that the TTR silencer has been effective in alleviating the signs and symptoms of CM, and that the patients should continue with their treatment plan. Full article

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive form of restrictive cardiomyopathy caused by the misfolding and deposition of transthyretin protein. What was once a condition that had little by way of treatment other than liver transplantation has now become a manageable disease due to revolutionary novel therapies. This review outlines therapeutic strategies aimed at halting or reversing disease progression. Current approaches include transthyretin (TTR) stabilizers such as tafamidis and acoramidis, as well as TTR silencers such as vutisiran. In addition, novel therapies under clinical investigation are emerging, such as gene-editing strategies and monoclonal antibodies targeting amyloid deposits. The aim of this paper is to investigate the current literature and ongoing clinical trials exploring treatment options for ATTR-CM. Transthyretin stabilizers and RNA silencers improve survival, functional capacity, and quality of life. Early-phase studies of gene-editing and monoclonal antibody therapies demonstrate promising amyloid-lowering effects. Stabilizers and silencers continue to constitute the standard therapy, while gene-editing and monoclonal antibodies offer potential as future treatments. The advent of a multitude of therapies for ATTR-CM holds promise for a future of targeted, personalized medicine for the treatment of this not-so-uncommon cause of heart failure. Full article

Background/Objectives: Anti-IgLON5 disease is a neurological disorder characterized by the presence of autoantibodies directed against the neuronal cell adhesion protein IgLON5. Pathophysiology involves both autoimmune inflammation and neurodegenerative processes. The most common causes of death are sudden death, central hypoventilation, dysphagia, and aspiration. However, the high rate of largely unclear sudden deaths calls for further research in this area. Methods: We performed a systematic search of the literature on causes of death in anti-IgLON5 disease following the PRISMA guidelines. In addition, we present a new case that was followed up in our clinic until death. Results: Of 258 publications with anti-IgLON5 disease, 21 publications comprising 61 cases that reported the causes of death were included in the analysis. The most common cause of death was death due to complications at 36.1%, followed by sudden death, accounting for 32.8% of the cases. Other causes include respiratory, cardiac, and unknown causes. The patient presented here as a case report was also diagnosed with cardiac amyloidosis and died from a cardiac cause of sudden death. Conclusions: Sudden death in anti-IgLON5 disease is one of the most common causes of death in the literature. A progressive neurodegenerative process in the brain stem causing central hypoventilation is generally assumed as a major causative factor. The case reported here had concomitant cardiac amyloidosis, which may raise the question as to whether unrecognized cardiac causes, which are not routinely screened for in this population, might represent another cause of sudden death, which would have important therapeutic implications. Full article

As an important representation form of three-dimensional scenes, the point cloud contains rich geometry and attribute information. The video-based point cloud compression standard (V-PCC) divides and projects three-dimensional data directionally onto a two-dimensional plane. The generated geometric and attribute graphs contain occupied pixels obtained by projection and unoccupied pixels used for smooth filling. Among them, the non-occupied pixels have no practical effect on the reconstructed point cloud. However, in the process of encoding bitrate allocation, V-PCC still uses the original bitrate control method, resulting in insufficient bitrate utilization efficiency. To this end, this paper proposes a method for optimizing the unoccupied pixels of point cloud videos based on V-PCC and jointly controlling the coding rate of geometries and attribute graphs. For geometric graphs, this paper improves the allocation of bitrate weights based on whether the encoded blocks contain non-occupied pixels and the proportion of occupied pixels, and stops allocating bitrates to encoded blocks that are all non-occupied pixels. For the attribute graph, the input pixel improvement algorithm is designed by using the occupation map, and the invalid unoccupied pixel information is cavitation. Experiments show that under the All Intra configuration, compared with the original scheme, this method reduces the Geom.BD-GeomRate by an average of 15.67% and 16.68%, respectively, in the point-to-point D1 and point-to-face D2 metrics. The end-to-end BD-AttrRate is reduced by an average of 4.38%, 0.68%, and 1.74%, respectively. Overall, the average savings are 29.88%, 31.50%, 5.50%, 2.66%, and 3.34%, respectively, achieving bitrate optimization and effectively controlling encoding loss. Full article

Transthyretin amyloidosis (ATTR) is a disease caused by the deposition of transthyretin-derived fibrils in the body. Despite extensive research conducted over the years, there are currently only four drugs available in clinical use to treat this condition, two of which are repurposed drugs used off-label. However, these treatments present several limitations; therefore, there is an urgent need for new therapeutic options. In this context, dietary supplements containing natural compounds capable of stabilizing the transthyretin (TTR) protein could represent a promising approach to contrast the disease progression, potentially supporting the therapeutic effects of the aforementioned drugs. In light of this, the present review highlights and analyzes the natural compounds that have most recently been reported in the literature as TTR stabilizers. In particular, the studies elucidating the potential of these compounds in the treatment of ATTR, along with the available crystallographic data explaining their binding mode to TTR, are reported. Overall, although the use of natural compounds as supplements shows promise in managing ATTR, further research is still needed to explore its feasibility and confirm its effectiveness. Hopefully, this work will help shed light on these issues and serve as a useful starting point for the development of new strategies to treat this disease. Full article

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype. Full article

Transthyretin-related (ATTR) amyloidosis is a progressive, multisystem disease caused by the extracellular deposition of misfolded transthyretin (TTR) monomers as insoluble amyloid fibrils. Clinical manifestations vary widely and may include cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN), or mixed phenotypes. The condition is increasingly recognized as an underdiagnosed contributor to heart failure, particularly in elderly patients. ATTR amyloidosis exists in two major forms: hereditary (ATTRv), resulting from mutations in the TTR gene, and wild-type (ATTRwt), typically affecting men over 70 years of age. Advances in disease understanding have led to a paradigm shift in management, with the introduction of targeted therapies that slow disease progression and improve prognosis. First-generation therapies such as tafamidis have demonstrated survival benefits in ATTR-CM. More recently, second-generation agents—such as the TTR stabilizer acoramidis and RNA silencers including vutrisiran and eplontersen—have shown promising efficacy in clinical trials. Additional strategies under investigation include gene editing and monoclonal antibodies targeting TTR amyloid deposits. This review outlines current diagnostic strategies and therapeutic options for ATTR amyloidosis, emphasizing the need for early detection and individualized treatment approaches. The expanding therapeutic landscape highlights the importance of accurate phenotyping and timely intervention to optimize clinical outcomes. Full article

Background/Objectives: Having serum biomarkers available for cardiac transthyretin amyloidosis (ATTR-CA) would be beneficial for diagnosis and prognosis. This study aimed to identify potential ATTR-CA biomarkers through proteomic analysis. Patients and Methods: Serum proteomic analyses were conducted on 15 ATTR-CA patients before receiving treatment, 11 ATTR-CA patients who had received tafamidis treatment for at least six months, and 13 patients with suspected cardiac amyloidosis who were later ruled out. All patients underwent blood tests, standard 12-lead electrocardiography, transthoracic echocardiography, and ^99mTc-DPD scintigraphy. Results: Proteomic analysis revealed significant differences in protein levels among the study groups. Key findings revealed increased levels of several proteins, including ceruloplasmin, apolipoprotein E, SERPINA1, and cDNA FLJ54111 (which is highly similar to serum transferrin), in ATTR-CA patients before receiving specific treatment. There was also a reduction in prothrombin, transferrin, CD14, and alpha-2-macroglobulin. In the ATTR-CA group treated with tafamidis, elevated levels of SERPINA1, paraoxonase 1, and complement C2 were observed. Notably, levels of cDNA FLJ54111 and SERPINA3 were reduced in this group. Compared to the control group, patients with ATTR-CA exhibited higher levels of ceruloplasmin, SERPINA3, and VCAM1, as well as lower levels of ApoA-I, ApoA-II, clusterin, and gelsolin. Controls exhibited elevated levels of transthyretin and prothrombin. Conclusions: This study identified candidate serum biomarkers for diagnosing ATTR-CA and monitoring the effectiveness of tafamidis treatment. Full article

Background: Transthyretin amyloidosis is a multi-system disease that may manifest as cardiomyopathy (ATTR-CM) and/or polyneuropathy. Both disease manifestations are associated with autonomic dysfunction. However, the prevalence of autonomic dysfunction in ATTR-CM remains to be evaluated. Methods: Within the scope of a prospective ATTR-CM registry, the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire was applied to consecutive patients between November 2022 and November 2024. Baseline characteristics are described, and associations of the COMPASS-31 score with markers of disease severity were assessed. Kaplan–Meier analysis was utilized to assess the COMPASS-31 score’s association with a combined endpoint of all-cause mortality and heart failure-related hospitalizations. Results: A total of 129 ATTR-CM patients [81.7 years (IQR: 77.4–84.3), 108 male (83.7%)] were included in the final study cohort. After stratification using the COMPASS-31 median [14 points, interquartile range (IQR): 6–29], statistically significant differences with regard to New York Heart Association (NYHA) stage and the Kansas City Cardiomyopathy Questionnaire (KCCQ) were observed. Furthermore, the COMPASS-31 score was moderately correlated with the KCCQ score in Spearman correlation analysis (r = −0.55, p < 0.001). The primary endpoint occurred in 16 patients (13 HF-hospitalizations/3 deaths) after 6.3 (IQR: 2.8–17.1) months. In Kaplan–Meier analysis, a COMPASS-31 score above the median of 14 was also associated with the primary endpoint of all-cause mortality and HF-related hospitalization (log-rank p = 0.047). Conclusions: Autonomic dysfunction is highly prevalent in ATTR-CM, affecting almost two-thirds of patients. As the presence of autonomic dysfunction is likely associated with more severely impaired quality of life, routine screening for this disease manifestation of transthyretin amyloidosis may be advisable. Full article

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant disorder caused by pathogenic variants in the TTR gene. The destabilized mutant form of the transport protein transthyretin (TTR) leads to the extracellular deposition of amyloid fibrils. Materials and Methods: A 65-year-old female patient with suspected clinical diagnosis of ATTR was referred for genetic testing for pathogenic variants in the TTR gene after physical, neurological and cardiac testing. Results: The patient had had cardiac dysfunction, atrial fibrillation and supraventricular tachycardia for around 10 years before the suspected and confirmed cardiac amyloidosis. The molecular genetic testing showed a heterozygous pathogenic variant in exon 3 of the TTR gene NM_000371.4(TTR): c.258A>C, p.(Glu86Asp). This variant in the TTR gene is classified as pathogenic in accordance with ACMG/AMP for the interpretation of variants. Conclusions: The presented case of a very rare pathogenic variant in the TTR gene displays the valuable role of genetic testing on the way to clarifying a diagnosis. Full article

Background: Bisphosphonate scintigraphy (BS) is a recognized tool for diagnosing amyloid transthyretin cardiomyopathy (ATTR-CA). However, its sensitivity for rare transthyretin (TTR) variants, like Glu54Gln, remains underexplored. Methods: This was a retrospective descriptive study including all known patients with the Glu54Gln variant diagnosed between 2017 and 2023 in Romania, aiming to evaluate the diagnostic performance of BS in Glu54Gln ATTR–CA. Results: All symptomatic patients (n = 22) with histologically confirmed ATTR-CA had positive BS results (100% sensitivity). No false negatives were observed in asymptomatic carriers (n = 4). The Perugini visual score correlated with disease severity, with grade 3 scores associated with advanced cardiac involvement. We proposed a new parameter, heart-to-liver-uptake (H/L) ratio, which proved a strong positive correlation with both the heart-to-contralateral-uptake (H/CL) ratio (R² = 0.768, p < 0.001) and interventricular septum thickness (R² = 0.584, p < 0.001) and a weak correlation with the global longitudinal strain (R² = 0.212, p = 0.023). Conclusions: BS demonstrates high diagnostic accuracy for Glu54GlnATTR-CA, underscoring its utility in early diagnosis and clinical management. The H/L ratio presents a novel approach to semiquantitative analysis of bisphosphonate uptake in cardiac amyloidosis, potentially addressing key limitations of the traditional H/CL ratio. Full article

Background: Carpal tunnel syndrome (CTS) has emerged as an early indicator of cardiac amyloidosis (CA) caused by transthyretin-associated (ATTR) mutations, possibly linked to adverse cardiovascular outcomes. This case series examines the relationship between idiopathic CTS and CA imaging diagnosis. Methods: Twenty-two patients from the cross-sectional study CarPoS (NCT05409833) were included. These patients underwent physical evaluation, laboratory exams, electrocardiography, echocardiography, cardiac magnetic resonance (CMR) imaging, and scintigraphy with ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Results: Four of the twenty-two patients included had ATTR cardiomyopathy. These patients presented left-ventricle hypertrophy and signs of infiltrative cardiomyopathy in echocardiograms and late gadolinium enhancement in CMR images without having any cardiovascular symptoms. Conclusions: Our findings suggest a high prevalence of CA in patients with bilateral idiopathic CTS, highlighting the importance of screening for CA in patients with CTS. Early detection could significantly impact patient prognosis, underscoring the need for further research into diagnostic and therapeutic strategies. Full article

Background/Objectives: A 43-year-old male presented with neurological symptoms and asymptomatic cardiac dysfunction, left ventricular hypertrophy, and impaired global longitudinal strain with apical sparing, associated with elevated NT-proBNP. Methods: Multimodality imaging (bone scintigraphy and cardiac magnetic resonance) revealed cardiac amyloid deposition. Genetic testing confirmed variant transthyretin amyloidosis (ATTR) with mixed phenotype. Results: Treatment with tafamidis 20 mg for stage I polyneuropathy, available at that moment, was initiated with good neurological outcome. Three years later, cardiac function deteriorated, following a moderate COVID-19 infection, with heart failure symptoms and reduced ventricular and atrial functions. For progressive ATTR cardiomyopathy, we intensified therapy to tafamidis free acid 61 mg, associated with SGLT2 inhibitor, spironolactone, and furosemide with subsequent improvements of symptoms and stabilization of imaging findings. Conclusions: This case emphasizes the importance of multimodal imaging in early detection, monitoring, and guiding individualized management in ATTR cardiomyopathy. Full article

Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. Methods: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as “cardiac amyloidosis”, “cardiac amyloidosis from transthyretin”, “cardiomyopathy”, “transthyretin”, “immunoglobulin light-chain amyloidosis”, and “familial amyloidosis” were used. Relevant clinical trials and guideline-based management recommendations were also included. Results: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. Conclusions: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease. Full article

Background/Objectives: In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), the effect of tafamidis on right ventricular (RV) dysfunction has been poorly investigated. The purpose of this study was to evaluate the effect of tafamidis on RV free wall global longitudinal strain (RV FW-GLS) and right ventricular and pulmonary artery (RV-PA) coupling over 12 months of treatment. Methods: Ninety-three patients with ATTR-CM treated with 61 mg of tafamidis daily who underwent multimodality imaging evaluation at baseline by cardiovascular magnetic resonance (CMR) and speckle-tracking echocardiography were retrospectively studied. The 12-month follow-up included an echocardiographic assessment of RV FW-GLS and RV-PA coupling. RV reverse remodeling was defined as a >10% improvement in RV FW-GLS and/or in RV-PA coupling from baseline. RV-PA coupling was assessed using the tricuspid annular plane systolic excursion/ pulmonary artery systolic pressure (TAPSE/PASP) ratio. Results: Over 12 months of tafamidis treatment, RV reverse remodeling was documented in 22.6% of patients. In these patients, RV FW-GLS improved significantly from 14.5 ± 2.1% to 17.3 ± 2%, p < 0.001, whereas the TAPSE/PASP ratio improved from 0.42 ± 0.05 mm/mmHg to 0.54 ± 0.07 mm/mmHg, p = 0.001. Patients who experienced RV reverse remodeling were at an earlier stage of disease prior to tafamidis treatment with less dilated RV and less severe RV-PA uncoupling (TAPSE/PASP ratio: 0.43 ± 0.06 mm/mmHg vs. 0.39 ± 0.06 mm/mmHg, p = 0.040). CMR-derived baseline RV end-systolic volume (HR 0.83, 95% CI 0.73–0.94, p = 0.005) and NT-proBNP (HR 0.989, 95% CI 0.988–0.999, p = 0.024) were the strongest independent predictors of RV reverse remodeling, followed by PASP (HR 0.82, 95% CI 0.69–0.98, p = 0.030). Conclusions: Patients with ATTR-CM treated with tafamidis at an earlier stage of the disease experienced RV reverse remodeling with significant improvement in RV FW-GLS and RV-PA coupling. Full article