Publications by authors named "Carol Whelan"
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.
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
- 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
- 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
- - The study investigates cardiovascular autonomic dysfunction in individuals with hereditary transthyretin amyloidosis, revealing that 27% reported symptoms at disease onset, increasing to 78% at the first evaluation (T1) after 4.5 years.
- - A total of 124 individuals participated, with cardiovascular autonomic failure found in 75% of symptomatic patients and 64% of asymptomatic TTR variant carriers, highlighting a significant underestimate of autonomic issues in early stages.
- - The findings suggest that autonomic dysfunction can be an early indicator of disease progression, with a faster progression rate observed in individuals reporting autonomic symptoms, emphasizing the need for routine autonomic function testing for better diagnosis and monitoring.
Article Synopsis
- * It analyzed data from 2,141 ATTR-CA patients, revealing that those who walked less than 350 meters on the 6MWT had a significantly higher mortality risk, with mortality rates increasing as walking distance decreased.
- * The findings suggest that monitoring changes in 6MWT performance can enhance risk assessment and disease progression understanding, offering valuable insights beyond conventional measures like N-terminal pro-B-type natriuretic peptide levels.
Article Synopsis
- Transthyretin cardiac amyloidosis (ATTR-CA) is a serious heart condition that can progress at different rates among patients, making it hard to track disease advancement.
- This study analyzed the significance of rising levels of NT-proBNP and increased need for diuretics as predictors of worsening heart function over one year in a large sample of ATTR-CA patients.
- Results showed that increases in NT-proBNP and diuretic use were both strongly linked to increased mortality risk, highlighting the importance of these markers for monitoring patients' health outcomes.
Article Synopsis
- Cardiopulmonary exercise testing (CPET) is important for evaluating heart failure but lacks data specifically for patients with transthyretin (ATTR) amyloidosis.
- The study aimed to characterize the functional capabilities of ATTR amyloidosis patients using CPET and explore how these relate to the severity of cardiac amyloid deposits and patient prognosis.
- Results indicated that functional impairment was common, particularly in patients with ATTR-CM and ATTR-mixed phenotypes, highlighting issues like decreased oxygen consumption and inefficiencies in exercise performance across the different disease types.
Article Synopsis
- Transthyretin cardiac amyloidosis (ATTR-CA) is a serious heart condition, and this study aimed to understand the relationship between various blood biomarkers and patient prognosis.
- Researchers examined 2,566 patients with ATTR-CA, finding high rates of anemia, urea, hyperbilirubinemia, and elevated troponin levels, which increased with disease severity.
- The study concluded that several biomarkers, especially anemia and elevated troponin levels, are independently linked to higher mortality rates in patients, with variations based on genetic factors and heart function.
Article Synopsis
- Cardiac involvement is crucial in systemic amyloidosis outcomes, with this study investigating how myocardial ischaemia affects cellular damage using advanced imaging and tissue analysis.
- The study involved 93 patients with cardiac amyloidosis and 97 controls, revealing that those with amyloidosis had significantly lower myocardial blood flow during stress tests compared to other groups.
- Histopathological analysis showed vascular abnormalities and reduced capillary density in cardiac tissue from amyloid patients, highlighting a complex relationship between amyloid infiltration and ischaemia.
Article Synopsis
- Amyloidogenic serum free light chains (sFLCs) contribute to the worsening of AL amyloidosis, and a new testing method called FLC-MS shows improved sensitivity for detecting disease remnants.
- In a study involving 487 patients, FLC-MS identified that 16.6% and 20.7% were negative for sFLCs at 6 and 12 months post-treatment, respectively, highlighting its ability to correlate with better survival rates and organ response.
- The findings indicate that FLC-MS negativity is a strong predictor of positive outcomes in patients, suggesting it may become the new standard for assessing treatment responses in AL amyloidosis.
Article Synopsis
- Transthyretin cardiac amyloidosis (ATTR-CA) often occurs alongside chronic kidney disease, with albuminuria being common and linked to worse health outcomes; however, its exact impact on ATTR-CA is not fully understood.
- In a study of 1,181 ATTR-CA patients, nearly 48% had albuminuria, which was associated with more severe heart issues marked by elevated cardiac biomarkers and poorer heart function compared to those with normal protein levels in urine.
- Both microalbuminuria and macroalbuminuria independently predicted higher mortality rates, with significant risks evident even in patients without other complicating conditions like hypertension or diabetes; an increase in urinary albumin levels over 12 months also indicated increased
Article Synopsis
- - ATTR-CM is a form of heart failure linked to a specific TTR gene mutation (p.(V142I)) prevalent in 3-4% of individuals of African descent, potentially affecting 1.6 million people in the U.S.
- - A study analyzed 413 patients with this mutation, finding that they had significant heart functional impairment and lower 5-year survival rates compared to patients with wild-type ATTR-CM, emphasizing the seriousness of the condition.
- - The aggressive nature of p.(V142I)-ATTRv-CM was highlighted by findings of myocyte loss and widespread infiltration in the heart muscle, indicating a high risk for biventricular failure and poor patient outcomes.
These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies.
View Article and Find Full Text PDFImportance: Cardiac magnetic resonance (CMR) imaging-derived extracellular volume (ECV) mapping, generated from precontrast and postcontrast T1, accurately determines treatment response in cardiac light-chain amyloidosis. Native T1 mapping, which can be derived without the need for contrast, has demonstrated accuracy in diagnosis and prognostication, but it is unclear whether serial native T1 measurements could also track the cardiac treatment response.
Objective: To assess whether native T1 mapping can measure the cardiac treatment response and the association between changes in native T1 and prognosis.
Aims: The aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA).
Methods And Results: A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.
Background: Systemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden.
Objectives: The purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis.
Aims: To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease.
Methods And Results: A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.
Aims: Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive and fatal cardiomyopathy. Treatment options in patients with advanced ATTR-CM are limited to cardiac transplantation (CT). Despite case series demonstrating comparable outcomes with CT between patients with ATTR-CM and non-amyloid cardiomyopathies, ATTR-CM is considered to be a contraindication to CT in some centers, partly due to a perceived risk of amyloid recurrence in the allograft.
View Article and Find Full Text PDFBackground: Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined.
Objectives: This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging.
Methods: A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype.