Publications by authors named "Gillmore J"
Background: Proteomics is routinely used to type clinical amyloid deposits, and offers additional benefit of identifying genetic variants, which can be diagnostically useful. Reviewing the proteomics data for ATTR patients attending our Centre revealed an unusually large number of samples containing a rare pathogenic H90D TTR variant alongside the more common H90N variant.
Methods: These findings raised questions to their source.
Article Synopsis
- The study aimed to evaluate the effects of trimetazidine, an antianginal medication, on heart function in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt).
- Twenty-two participants were enrolled in a randomized, double-blind trial, comparing the effects of trimetazidine to a placebo over four weeks, measuring various cardiovascular and mitochondrial functions.
- The results showed no significant improvements in key cardiac measures, such as pulmonary artery wedge pressure or mitochondrial function, indicating that trimetazidine did not provide benefits to patients with ATTRwt compared to the placebo.
Background: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM.
View Article and Find Full Text PDFBackground: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE.
View Article and Find Full Text PDFBackground: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, often fatal disease. Nexiguran ziclumeran (nex-z) is an investigational therapy based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease) targeting the gene encoding transthyretin ().
Methods: In this phase 1, open-label trial, we administered a single intravenous infusion of nex-z to patients with ATTR-CM.
Background: The NEURO-TTRansform trial showed that after 66 weeks of treatment, eplontersen significantly reduced neuropathic impairment and improved quality of life (QoL) in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN). In this secondary analysis from NEURO-TTRansform, autonomic impairment, and the impact of eplontersen on autonomic impairment progression was evaluated through 85 weeks in patients randomised to eplontersen ( = 144) versus external placebo ( = 60; through Week 66 from the NEURO-TTR trial).
Methods: Change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) composite score, Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score, and the Neuropathy Symptoms and Change (NSC) total score was evaluated.
Article Synopsis
- - The study aimed to identify what changes in neuropathic impairment and quality of life (QoL) are important to patients with hereditary transthyretin amyloidosis and to evaluate if the drug eplontersen provides significant improvements compared to a placebo.
- - Researchers used data from the NEURO-TTRansform trial and various scoring systems to determine thresholds for meaningful differences, finding that eplontersen led to improvements that exceeded these thresholds in neuropathy, QoL, and nutrition measurements.
- - Results showed eplontersen provided significant clinical benefits, suggesting that these findings could influence future clinical practices and trials regarding treatment effectiveness for patients with this condition.
Importance: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.
Objective: To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.
Aims: Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis.
Methods And Results: The study population comprised 800 patients, of which 400 had light-chain CA (AL-CA) and 400 had transthyretin CA (ATTR-CA).
Article Synopsis
- Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a serious, progressive disease, and vutrisiran is a new treatment that works by reducing the production of transthyretin in the liver.
- In a double-blind trial involving 655 patients, those receiving vutrisiran had a lower risk of death and cardiovascular events compared to those on placebo, demonstrating significant efficacy.
- Vutrisiran also improved patient outcomes, showing less decline in walking distance and quality of life measurements over the study period compared to placebo.
Article Synopsis
- Cardiac amyloid infiltration significantly impacts survival in systemic light-chain (AL) amyloidosis, with guidelines suggesting early therapy changes for patients not responding well, regardless of cardiac amyloid severity.
- The study aimed to compare serum biomarkers, echocardiography, and cardiovascular magnetic resonance (CMR) with extracellular volume (ECV) mapping in understanding cardiac amyloid and its prognostic value.
- Findings revealed that ECV is a strong independent predictor of mortality, showing different relationships between the depth of hematological response and survival based on specific ECV thresholds over 1- and 6-month periods.
Article Synopsis
- Transthyretin cardiac amyloidosis (ATTR-CA) primarily impacts older adults with various chronic health issues, leading to significant physical and emotional difficulties.
- New drugs show promise in early treatment stages, prompting a need for thorough assessments of patients' functional abilities and quality of life.
- Incorporating comprehensive geriatric assessment tools into standard care can help identify early signs of frailty and improve management strategies for older ATTR-CA patients.
Article Synopsis
- Kidney light chain (AL) amyloidosis can lead to serious health issues including the need for kidney replacement therapy and increased mortality risk, with better outcomes linked to significant reductions in proteinuria after treatment.
- This study aimed to confirm how different levels of kidney response to treatment relate to patient survival, using data from 732 patients over several years.
- Results showed that deeper kidney responses within 6 months of treatment initiation were associated with significantly lower chances of needing kidney replacement therapy after 5 years.
Article Synopsis
- - Immunoglobin light chain (AL) amyloidosis is a rare disease mainly affecting the heart and kidneys through amyloid fibril buildup, making organ-specific evaluations crucial for understanding the disease's impact and guiding treatment.
- - To promote new treatment developments, the Amyloidosis Forum convened to create guidelines for clinical trials, focusing on identifying effective assessment measures particularly from the insights of the Renal Working Group.
- - Key recommendations include using estimated glomerular filtration rate (eGFR) and proteinuria to determine trial eligibility and track patient responses, while highlighting the importance of timely and accurate evaluation of treatment effects.
Article Synopsis
- The study investigates the role of beta-blockers in improving survival for patients with cardiac amyloidosis (CA), highlighting unclear efficacy and concerns about worsening heart failure symptoms.
- A systematic review and meta-analysis of 13 studies involving 4,215 CA patients concluded that beta-blocker therapy may be associated with reduced mortality, particularly in mixed ATTR-CM and AL-CM cases.
- However, the study notes significant limitations, such as a lack of information on the staging of CA, which may affect the findings' applicability.
Article Synopsis
- Wild-type transthyretin amyloid cardiomyopathy (ATTRwt) is connected to heart failure, with this study focusing on how cardiac performance and mitochondrial function relate to different disease stages.
- The research involved 47 patients diagnosed with ATTRwt and categorized into three groups based on disease severity, revealing significant issues like increased filling pressures during exercise even when resting pressures were normal.
- Findings indicated that patients exhibited reduced cardiac output and impaired mitochondrial function, suggesting a complex interplay between heart health and mitochondrial performance in ATTRwt patients.*
Article Synopsis
- This study aims to enhance the NAC staging system for transthyretin cardiac amyloidosis (ATTR-CA) by adding a new stage to better identify patients at high risk of early death.
- A new stage 4 was introduced based on NT-proBNP levels (≥10,000 ng/L), and results from 2042 patients showed significantly higher mortality rates for this group compared to lower stages.
- The findings suggest that patients in stage 4 may need more intensive treatment strategies due to their elevated risk of early mortality, which could also inform clinical trial designs.
Article Synopsis
- This study analyzed the effectiveness and tolerability of SGLT2 inhibitors in patients with transthyretin cardiomyopathy (ATTR-CM), a condition previously excluded from related clinical trials.
- Out of 2,356 ATTR-CM patients, 260 received SGLT2 inhibitors, and after matching for certain variables, it was found that SGLT2i treatment led to less deterioration in heart failure symptoms and better kidney function over time.
- The findings suggest that SGLT2i treatment not only had a low discontinuation rate but also significantly reduced the risks of all-cause mortality, cardiovascular mortality, and heart failure hospitalizations in these patients.
Article Synopsis
- Bortezomib is a common first-line treatment for systemic AL amyloidosis, and the study evaluates the effectiveness of a second-line therapy combining daratumumab, bortezomib, and dexamethasone (DVD) in patients previously treated with bortezomib.
- From a cohort of 116 patients undergoing second-line DVD, a significant percentage (69.8%) achieved a complete response (CR) or very good partial response (VGPR), with better outcomes observed in those who initially responded well to first-line bortezomib.
- The study also found that patients who received DVD due to inadequate response to first-line treatment had lower event-free survival
Article Synopsis
- A 56-year-old man experienced 2 years of worsening fatigue, weakness, and nocturnal bowel issues, leading to abnormal test results that suggested potential cardiac amyloidosis.
- His echocardiogram showed thickened heart walls, and additional scans indicated transthyretin amyloidosis (ATTR), despite finding Bence Jones protein in his urine.
- Diagnostic tests, including a bone marrow biopsy, confirmed amyloid presence, revealing a genetic mutation for hereditary ATTR but no signs of another type of amyloidosis (AL).
Article Synopsis
- Hereditary transthyretin amyloidosis (ATTRv) and wild-type ATTR amyloidosis (ATTRwt) are rare and progressive disorders characterized by the accumulation of amyloid fibrils in various organs, leading to significant health complications and unmet medical needs for patients.
- The Amyloidosis Forum, a partnership between the FDA and the Amyloidosis Research Consortium, recently discussed strategies for advancing drug development and clinical trial designs for ATTR amyloidosis, considering perspectives from various stakeholders.
- With the changing landscape of ATTR amyloidosis, reliance on historical control data is diminishing, highlighting the importance of using contemporary real-world data to inform clinical trial designs and address relevant clinical questions effectively.