62 results on '"Philip N Hawkins"'
Search Results
2. Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis
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Francisco Gama, Stefania Rosmini, Steve Bandula, Kush P. Patel, Paolo Massa, Catalina Tobon-Gomez, Karolin Ecke, Tyler Stroud, Mark Condron, George D. Thornton, Jonathan B. Bennett, Ashutosh Wechelakar, Julian D. Gillmore, Carol Whelan, Helen Lachmann, Stuart A. Taylor, Francesca Pugliese, Marianna Fontana, James C. Moon, Philip N. Hawkins, and Thomas A. Treibel
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Abstract
Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis.This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVPatients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVA total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCardiac amyloid burden quantified by ECV
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- 2022
3. Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping
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Adam Ioannou, Rishi K. Patel, Ana Martinez-Naharro, Yousuf Razvi, Aldostefano Porcari, David F. Hutt, Francesco Bandera, Tushar Kotecha, Lucia Venneri, Liza Chacko, Paolo Massa, Melissa Hanger, Daniel Knight, Charlotte Manisty, James Moon, Cristina Quarta, Helen Lachmann, Carol Whelan, Peter Kellman, Philip N. Hawkins, Julian D. Gillmore, Ashutosh Wechelakar, and Marianna Fontana
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine - Published
- 2023
4. Comparison of 99mTc-DPD Scintigraphy, CMR Imaging, and Echocardiography in Patients With V30M-Associated Hereditary Transthyretin Amyloidosis
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Henry Somers, Ubaid Tanzim, Aldostefano Porcari, Yousuf Razvi, Tamer Rezk, Rishi Patel, Liza Chacko, Dorota Rowczenio, Janet A. Gilbertson, David F. Hutt, Philip N. Hawkins, Marianna Fontana, Julian D. Gillmore, Somers, Henry, Tanzim, Ubaid, Porcari, Aldostefano, Razvi, Yousuf, Rezk, Tamer, Patel, Rishi, Chacko, Liza, Rowczenio, Dorota, Gilbertson, Janet A., Hutt, David F., Hawkins, Philip N., Fontana, Marianna, and Gillmore, Julian D.
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Amyloid Neuropathies, Familial ,Echocardiography ,Prealbumin ,Predictive Value of Test ,Radiology, Nuclear Medicine and imaging ,Radiopharmaceuticals ,Radionuclide Imaging ,Cardiology and Cardiovascular Medicine ,Cardiomyopathie ,Human - Abstract
N/A
- Published
- 2022
5. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis
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Carolina Donà, George Thornton, Francesca Pugliese, James C. Moon, Simon Kennon, Marianna Fontana, Julia Mascherbauer, Philip N. Hawkins, Muhiddin Ozkor, Andreas A. Kammerlander, Guy Lloyd, James D. Newton, Nikant Sabharwal, Thomas A. Treibel, Tim Wollenweber, Andrew Kelion, Christian Nitsche, Paul Scully, Michael J. Mullen, Leon Menezes, Matthias Koschutnik, Kush Patel, and Nida Ahmed
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Diastole ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Valve replacement ,Internal medicine ,Prevalence ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Radionuclide Imaging ,Ventricular remodeling ,Aged ,Aged, 80 and over ,Troponin T ,business.industry ,Amyloidosis ,Aortic Valve Stenosis ,Right bundle branch block ,medicine.disease ,United States ,Stenosis ,Cardiac amyloidosis ,Austria ,Concomitant ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). Objectives This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. Methods Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. Results A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p Conclusions Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.
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- 2021
6. Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression
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Julian D. Gillmore, Janet A. Gilbertson, Ana Martinez-Naharro, James C. Moon, Thirusha Lane, Peter Kellman, David F. Hutt, Carol J. Whelan, Philip N. Hawkins, Aviva Petrie, Liza Chacko, Svetla G. Strehina, Dorota Rowczenio, and Marianna Fontana
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Amyloid Neuropathies, Familial ,Pathology ,medicine.medical_specialty ,Amyloid ,business.industry ,Amyloidosis ,030204 cardiovascular system & hematology ,equipment and supplies ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Extracellular fluid ,cardiovascular system ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,RNA, Small Interfering ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,Cardiac magnetic resonance ,business ,human activities ,Retrospective Studies - Abstract
The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM).Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain.Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a "TTR-stabilizing" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results.Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%).Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran.
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- 2021
7. Identifying Cardiac Amyloid in Aortic Stenosis
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Simon Kennon, Neil Hartman, Muhiddin Ozkor, Francesca Pugliese, James C. Moon, Philip N. Hawkins, Bunny Saberwal, Kush Patel, Rebecca K. Hughes, Thomas A. Treibel, Michael J. Mullen, Ernst Klotz, João L. Cavalcante, Nikant Sabharwal, João B Augusto, Paul Scully, James D. Newton, Andrew Kelion, Leon Menezes, Charlotte Manisty, George Thornton, and Guy Lloyd
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medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Plasma cell dyscrasia ,Computed tomography ,030204 cardiovascular system & hematology ,medicine.disease ,Control subjects ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Stenosis ,0302 clinical medicine ,Cardiac amyloidosis ,Bone scintigraphy ,Valve replacement ,medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine - Abstract
Objectives The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid. Background AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV). Methods Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition. Results A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p Conclusions ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well.
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- 2020
8. Noncontrast Magnetic Resonance for the Diagnosis of Cardiac Amyloidosis
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Michele Boldrini, Cristina Quarta, Aviva Petrie, Ashutosh D. Wechalekar, James C. Moon, Peter Kellman, Andrea Baggiano, Julian D. Gillmore, Tushar Kotecha, Tamer Rezk, Maurizio Gritti, Daniel S Knight, Philip N. Hawkins, Helen J. Lachmann, Marianna Fontana, Ana Martinez-Naharro, Gianluca Pontone, and Stefano Perlini
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renal failure ,medicine.medical_specialty ,accuracy ,amyloidosis ,cardiovascular magnetic resonance ,native T1 mapping ,Population ,Settore MED/11 - Malattie dell'Apparato Cardiovascolare ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,education ,Prospective cohort study ,education.field_of_study ,medicine.diagnostic_test ,biology ,business.industry ,Amyloidosis ,Area under the curve ,Magnetic resonance imaging ,medicine.disease ,Transthyretin ,Cardiac amyloidosis ,Heart failure ,biology.protein ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives This study aimed to assess the diagnostic use of native T1 to detect cardiac amyloidosis (CA) in a large prospective cohort of patients referred for suspected systemic amyloidosis. Background CA is a progressive and fatal underdiagnosed cause of heart failure. Cardiovascular magnetic resonance (CMR) has emerged as an extremely useful test for the non-invasive diagnosis of CA, but administration of contrast is still required to make a diagnosis. Methods In this study, 868 patients with suspected CA referred between 2015 and 2017 underwent CMR with late gadolinium enhancement (LGE), T1 mapping, and an array of clinical investigations. Results The final diagnosis was cardiac light-chain (AL) amyloidosis in 222, cardiac transthyretin (ATTR) amyloidosis in 214, and no cardiac involvement in 427 cases. T1 was significantly elevated in both types of CA and this was associated with high diagnostic accuracy in the overall population (area under the curve, 0.93). A native T1 1,164 ms was associated with 98% positive predictive value for CA. We propose the use of these cut-offs to exclude or confirm CA and to restrict the administration of contrast only to patients with intermediate probability (native T1 between 1,036 and 1,164 ms), 58% of patients in this population. Conclusions Native myocardial T1 enables diagnosis of CA to be made without need for gadolinium contrast in a large proportion of patients with suspected systemic amyloidosis. We propose a diagnostic algorithm for non-contrast CMR applicable to patients with suspected amyloidosis.
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- 2020
9. Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction
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Tim Lockie, Hui Xue, Roby Rakhit, Ana Martinez-Naharro, Sven Plein, Deven Patel, Sundeep Kalra, Gerry Coghlan, Daniel R. Knight, Niket Patel, James C. Moon, Tushar Kotecha, Peter Kellman, Philip N. Hawkins, Marianna Fontana, and Michele Boldrini
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Blood flow ,Fractional flow reserve ,030204 cardiovascular system & hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,Coronary arteries ,Coronary artery disease ,03 medical and health sciences ,Stenosis ,0302 clinical medicine ,medicine.anatomical_structure ,Internal medicine ,Angiography ,medicine ,Cardiology ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Perfusion - Abstract
Objectives This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. Background Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. Methods Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. Results Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p Conclusions This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.
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- 2019
10. The Authors’ Reply
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Francesco Bandera, Raffaele Martone, Liza Chacko, Sharmananthan Ganesananthan, Janet A. Gilbertson, Markella Ponticos, Thirusha Lane, Ana Martinez-Naharro, Carol Whelan, Cristina Quarta, Dorota Rowczenio, Rishi Patel, Yousuf Razvi, Helen Lachmann, Ashutosh Wechelakar, James Brown, Daniel Knight, James Moon, Aviva Petrie, Francesco Cappelli, Marco Guazzi, Luciano Potena, Claudio Rapezzi, Ornella Leone, Philip N. Hawkins, Julian D. Gillmore, and Marianna Fontana
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,NO - Published
- 2021
11. Myocardial Edema and Prognosis in Amyloidosis
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Thomas A. Treibel, Peter Kellman, Marianna Fontana, Philip N. Hawkins, Rohin Francis, Amna Abdel-Gadir, Roby Rakhit, Ana Martinez-Naharro, James C. Moon, Julian D. Gillmore, Daniel S Knight, Ashutosh D. Wechalekar, Stefania Rosmini, Mary N. Sheppard, Giulia Zumbo, Janet A. Gilbertson, Tushar Kotecha, Heerajnarain Bulluck, Viviana Maestrini, and Sabrina Nordin
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Adult ,Male ,medicine.medical_specialty ,Myocardial edema ,030204 cardiovascular system & hematology ,Gene mutation ,Asymptomatic ,Gastroenterology ,030218 nuclear medicine & medical imaging ,T2 mapping ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,London ,medicine ,AL amyloidosis ,Edema ,Humans ,Prealbumin ,CMR ,Aged ,amyloidosis ,cardiology and cardiovascular medicine ,Aged, 80 and over ,medicine.diagnostic_test ,biology ,business.industry ,Myocardium ,Amyloidosis ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Transthyretin ,Cardiac amyloidosis ,biology.protein ,Female ,medicine.symptom ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis.The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis.The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 onMyocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67).Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.
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- 2018
12. P-024: Early relapse is an adverse prognostic marker in systemic immunoglobulin light chain (AL) Amyloidosis
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Marianna Fontana, Helen J. Lachmann, Shameem Mahmood, Philip N. Hawkins, Sriram Ravichandran, Jullian Gillmore, Brendan Wisniowski, Ashutosh D. Wechalekar, Ana Martinez-Naharro, Carol J. Whelan, Steven Law, and Darren Foard
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Bortezomib ,Plasma cell dyscrasia ,Hematology ,Disease ,medicine.disease ,Clinical trial ,Immunoglobulin Light-chain Amyloidosis ,Internal medicine ,Cohort ,Monoclonal ,AL amyloidosis ,Medicine ,business ,medicine.drug - Abstract
Background Systemic Immunoglobulin light chain amyloidosis (AL) is a protein-misfolding disorder associated with an underlying monoclonal B-cell or plasma cell dyscrasia. There is little information on how response durability impacts outcomes. It is conceivable that early relapse may confer an adverse prognosis in AL, like in Myeloma. Here, we test the above hypothesis and analyse the factors affecting response durability in a cohort of AL patients treated with frontline Bortezomib. Methods All patients treated with frontline Bortezomib in 2010-2019 are included in the analysis. Patients with primary refractory disease, those with a continuing response but ≤ 24 months follow up, and those who received 2nd line therapy for reasons other than progression are excluded from the analysis. We defined early relapse (ER) as PFS ≤ 24 months. Results 560 patients are included in this analysis. 250 (44.6%) and 310 (55.4%) patients had ER and LR, respectively. The ER group had more advanced cardiac disease (p 20% (p=0.021), ≥ VGPR after 1st line (p 20%, and dFLC Conclusions In conclusion, these data identify a high-risk group of patients who relapse early and have a poorer survival (irrespective of their initial response). The depth of response to the initial treatment is a critical determinant of response durability. The early relapses should be considered for clinical trials that can identify treatments with the potential to overcome the high-risk biology of the disease.
- Published
- 2021
13. Magnetic Resonance in Transthyretin Cardiac Amyloidosis
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Peter Kellman, David F. Hutt, James C. Moon, Rohin Francis, Carol J. Whelan, Stefania Rosmini, Marianna Fontana, Julian D. Gillmore, Ana Martinez-Naharro, Daniel S Knight, Philip N. Hawkins, Candida Cristina Quarta, Giulia Zumbo, Amna Abdel-Gadir, Tamer Rezk, Thomas A. Treibel, Tushar Kotecha, and Heerajnarain Bulluck
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Male ,medicine.medical_specialty ,Magnetic Resonance Imaging, Cine ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,030218 nuclear medicine & medical imaging ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,AL amyloidosis ,Humans ,cardiovascular diseases ,Ventricular remodeling ,Aged ,Retrospective Studies ,Amyloid Neuropathies, Familial ,Ejection fraction ,business.industry ,Myocardium ,Amyloidosis ,Hypertrophic cardiomyopathy ,Middle Aged ,Prognosis ,medicine.disease ,Cardiac amyloidosis ,Heart failure ,cardiovascular system ,Cardiology ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Cardiac transthyretin amyloidosis (ATTR) is an increasingly recognized cause of heart failure. Cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) and T1 mapping, is emerging as a reference standard for diagnosis and characterization of cardiac amyloidosis. Objectives The authors used CMR with extracellular volume fraction (ECV) measurement to characterize cardiac involvement in relation to outcome in ATTR. Methods Subjects comprised 263 patients with cardiac ATTR corroborated by grade 2 to 3 99mTc-DPD (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid) cardiac uptake, 17 with suspected cardiac ATTR (grade 1 99mTc-DPD), and 12 asymptomatic individuals with amyloidogenic transthyretin (TTR) mutations. Fifty patients with cardiac light-chain (AL) amyloidosis acted as disease comparators. Results Unlike cardiac AL amyloidosis, asymmetrical septal left ventricular hypertrophy (LVH) was present in 79% of patients with ATTR (70% sigmoid septum and 30% reverse septal contour), whereas symmetrical LVH was present in 18%, and 3% had no LVH. In patients with cardiac amyloidosis, the pattern of LGE was always typical for amyloidosis (29% subendocardial, 71% transmural), including right ventricular LGE (96%). During follow-up (19 ± 14 months), 65 patients died. ECV independently correlated with mortality and remained independent after adjustment for age, N-terminal pro-B-type natriuretic peptide, ejection fraction, E/E′, and left ventricular mass (hazard ratio: 1.164; 95% confidence interval: 1.066 to 1.271; p Conclusions Asymmetrical hypertrophy, traditionally associated with hypertrophic cardiomyopathy, was the commonest pattern of ventricular remodeling in ATTR. LGE imaging was typical in all patients with cardiac ATTR. ECV correlated with amyloid burden and was an independent prognostic factor for survival in this cohort of patients.
- Published
- 2017
14. High prevalence of recurrent nocturnal desaturations in systemic AL amyloidosis: a cross-sectional pilot study
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Leena George, Helen J. Lachmann, Christina C. Quarta, Julian D. Gillmore, Peter Smith, Ashutosh D. Wechalekar, Shameem Mahmood, Philip N. Hawkins, Milind Sovani, Carol J. Whelan, Marianna Fontana, and Sajitha Sachchithanantham
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Male ,medicine.medical_specialty ,Pilot Projects ,Polysomnography ,030204 cardiovascular system & hematology ,Nocturnal ,03 medical and health sciences ,Sleep Apnea Syndromes ,0302 clinical medicine ,Internal medicine ,Prevalence ,AL amyloidosis ,Macroglossia ,Humans ,Medicine ,Immunoglobulin Light-chain Amyloidosis ,Hypoxia ,Aged ,Aged, 80 and over ,biology ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,General Medicine ,Middle Aged ,Hypoxia (medical) ,medicine.disease ,Surgery ,Transthyretin ,Cross-Sectional Studies ,Cardiac amyloidosis ,biology.protein ,Cardiology ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objectives Cardiac involvement and/or macroglossia with soft tissue deposits are risk factors for central sleep apnoea (CSA) and obstructive sleep apnoea (OSA), and common features of systemic AL amyloidosis. Little data exist on the occurrence of sleep-disordered breathing (SDB) or recurrent nocturnal hypoxia in amyloidosis, which this study sought to investigate. Methods A total of 72 consecutive patients with systemic amyloidosis (mean age 69 years and mean BMI 25) were evaluated for occurrence of SDB, by overnight continuous pulse oximetry, and completed Epworth Sleepiness Score (ESS) and STOPBANG questionnaires. Patients included: AL cardiac (AL-C), AL macroglossia (AL-M), AL both (AL-CM) and transthyretin (ATTR). Results Mean overnight oxygen saturations were 93% (SD ± 2, 95% CI 87–96) with abnormal oximetry (4% oxygen desaturation index (ODI) >5/hour): AC-C 84%, AL-M 57%, AL-CM 62% and ATTR 47%. NYHA class directly correlated with a higher 4% ODI, NYHA class I vs 3, ( p = 0.01). Two-thirds of patients had STOPBANG scores >3 and abnormally high ESS scores (>10) were seen in up to 30% of patients. Conclusion Recurrent nocturnal hypoxaemia, suggestive of sleep-disordered breathing, is frequent in systemic AL amyloidosis. The higher incidence in cardiac amyloidosis highlights CSA and recurrent hypoxia as possible mechanisms for morbidity/mortality in these cases. A detailed polysomnography study is planned to clarify and further investigate these findings.
- Published
- 2017
15. The Authors Reply
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Andrea Baggiano, Michele Boldrini, Ana Martinez-Naharro, Tushar Kotecha, Aviva Petrie, Tamer Rezk, Maurizio Gritti, Cristina Quarta, Daniel S. Knight, Ashutosh D. Wechalekar, Helen J. Lachmann, Stefano Perlini, Gianluca Pontone, James C. Moon, Peter Kellman, Julian D. Gillmore, Philip N. Hawkins, and Marianna Fontana
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Magnetic Resonance Spectroscopy ,Humans ,Radiology, Nuclear Medicine and imaging ,Amyloidosis ,Cardiology and Cardiovascular Medicine - Published
- 2020
16. CMR-Verified Regression of Cardiac AL Amyloid After Chemotherapy
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James C. Moon, Julian D. Gillmore, Thirusha Lane, Peter Kellman, Shameem Mahmood, Daniel S Knight, Sajitha Sachchithanantham, Marianna Fontana, Giulia Zumbo, Philip N. Hawkins, Amna Abdel-Gadir, Carol J. Whelan, Ashutosh D. Wechalekar, Stefania Rosmini, Ana Martinez-Naharro, Thomas A. Treibel, and Helen J. Lachmann
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Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Amyloid ,medicine.medical_treatment ,Magnetic Resonance Imaging, Cine ,030204 cardiovascular system & hematology ,Immunoglobulin light chain ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Remission induction ,0302 clinical medicine ,Predictive Value of Tests ,medicine ,Humans ,Immunoglobulin Light-chain Amyloidosis ,Radiology, Nuclear Medicine and imaging ,Aged ,Retrospective Studies ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Remission Induction ,Monoclonal immunoglobulin ,Magnetic resonance imaging ,Middle Aged ,Amyloid fibril ,medicine.disease ,Treatment Outcome ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Systemic light-chain (AL) amyloidosis is characterized by interstitial deposition of aggregated misfolded monoclonal immunoglobulin light chains in the form of amyloid fibrils. Cardiac involvement is the main driver of prognosis. Brain natriuretic peptides and echocardiography are currently the
- Published
- 2018
17. Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis
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Shonit Punwani, Julian D. Gillmore, Stuart A. Taylor, Philip N. Hawkins, Steven K White, James C. Moon, Thomas A. Treibel, Marianna Fontana, Anna S Herrey, Steve Bandula, and Janet A. Gilbertson
- Subjects
Male ,Biopsy ,Contrast Media ,Severity of Illness Index ,Electrocardiography ,Natriuretic Peptide, Brain ,Extracellular space ,CMR ,Ultrasonography ,Ejection fraction ,medicine.diagnostic_test ,biology ,DynEQ-CT, Bolus-only Dynamic-Equilibrium Computed Tomography ,Amyloidosis ,RV, Right ventricle ,Heart ,Middle Aged ,Magnetic Resonance Imaging ,Troponin ,Radiology Nuclear Medicine and imaging ,cardiovascular system ,Cardiology ,Female ,ECV, Extracellular Volume fraction ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,Research Paper ,Adult ,AL amyloidosis, Immunoglobulin light-chain amyloidosis ,medicine.medical_specialty ,Cardiac-Gated Imaging Techniques ,Cardiac imaging techniques ,LV, Left ventricle ,LVH, Left ventricular hypertrophy ,Bone and Bones ,EQ-CMR, Equilibrium-infusion contrast Cardiovascular Magnetic Resonance ,Predictive Value of Tests ,Triiodobenzoic Acids ,Internal medicine ,TTR, Transthyretin protein ,Multidetector Computed Tomography ,medicine ,AL amyloidosis ,AS, Aortic Stenosis ,Humans ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,ATTR amyloidosis, Transthyretin amyloidosis ,Aged ,business.industry ,LGE, Late gadolinium enhancement ,Magnetic resonance imaging ,medicine.disease ,Peptide Fragments ,CCT ,ShMOLLI, Shortened Modified Look-Locker Inversion Recovery ,Bone scintigraphy ,Cardiac amyloidosis ,Case-Control Studies ,biology.protein ,Cardiac Imaging Techniques ,DPD, 3,3-diphosphono-1,2-propanodicarboxylicacid ,business ,Biomarkers - Abstract
Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p, Highlights • Cardiac involvement determines outcome in amyloidosis. • There is major unmet need for quantification of cardiac amyloid burden. • Dynamic Equilibrium CT (DynEQ-CT) is a 5-minute contrast-enhanced CT scan. • DynEQ-CT measures the extracellular volume fraction, which increases in amyloid. • DynEQ-CT has major potential for diagnosis and quantification of cardiac amyloidosis.
- Published
- 2015
18. The V122I Variant in Hereditary Transthyretin-Mediated Amyloidosis is Significantly Associated with Polyneuropathy
- Author
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Margaret M. Parker, Scott M. Damrauer, Catherine Tcheandjieu, David Erbe, Emre Aldinc, Philip N. Hawkins, Julian Gillmore, Leland E. Hull, Julie A. Lynch, Jacob Joseph, Simina Ticau, Alexander O. Flynn-Carroll, Aimee M. Deaton, Lucas D. Ward, Themistocles L. Assimes, Philip S. Tsao, Kyong-Mi Chang, Daniel J. Rader, Kevin Fitzgerald, Akshay K. Vaishnaw, Gregory Hinkle, and Paul Nioi
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2020
19. Identifying Mixed Phenotype: Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy
- Author
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Martha Grogan, John L. Berk, Ole B. Suhr, Verena Karsten, Anastasia McManus, John Vest, Christine Powell, Madeline Merkel, Daniel P. Judge, Arnt V. Kristen, Philip N. Hawkins, and Hollis Lin
- Subjects
Pathology ,medicine.medical_specialty ,biology ,business.industry ,Amyloidosis ,Cardiomyopathy ,nutritional and metabolic diseases ,macromolecular substances ,030204 cardiovascular system & hematology ,medicine.disease ,Phenotype ,nervous system diseases ,03 medical and health sciences ,Transthyretin ,0302 clinical medicine ,biology.protein ,Medicine ,In patient ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Polyneuropathy - Abstract
Identifying Mixed Phenotype : Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy
- Published
- 2019
20. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy
- Author
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Aisling Carr, Mary M. Reilly, Janice L. Holton, Philip N. Hawkins, Zane Jaunmuktane, Sebastian Brandner, Carol J. Whelan, M.R.B. Evans, Ashutosh D. Wechalekar, Julian Blake, D. Hutt, Ana L. Pelayo-Negro, Julian D. Gillmore, E. Heally, and Renata S Scalco
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Heart Diseases ,Amyloid ,Cardiomyopathy ,Familial amyloid cardiomyopathy ,medicine ,Humans ,Muscle, Skeletal ,Myopathy ,Genetics (clinical) ,Amyloid Neuropathies, Familial ,biology ,business.industry ,Myocardium ,Amyloidosis ,Peripheral Nervous System Diseases ,Middle Aged ,medicine.disease ,Transthyretin ,Amyloid Neuropathy ,Neurology ,Cardiac amyloidosis ,Pediatrics, Perinatology and Child Health ,biology.protein ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Hereditary transthyretin amyloidosis (ATTR) is a genetically and clinically heterogeneous disease manifesting with predominant peripheral and autonomic neuropathy; cardiomyopathy, or both. ATTR V122I is the most common variant associated with non-neuropathic familial amyloid cardiomyopathy. We present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment.
- Published
- 2015
21. Natural history and outcomes in localised immunoglobulin light-chain amyloidosis: a long-term observational study
- Author
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Ketna Patel, Shameem Mahmood, Marianna Fontana, Janet A. Gilbertson, Carol J. Whelan, Sajitha Sachchithanantham, Thomas Wagner, Philip N. Hawkins, Dorota Rowczenio, Julian D. Gillmore, Frank Bridoux, Helen J. Lachmann, Ashutosh D. Wechalekar, Rabya Sayed, and Christopher P. Venner
- Subjects
Male ,medicine.medical_specialty ,Biopsy ,Gastroenterology ,Immunoglobulin Light-chain Amyloidosis ,Internal medicine ,medicine ,AL amyloidosis ,Humans ,Longitudinal Studies ,Survival rate ,Aged ,Aged, 80 and over ,Hematology ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Middle Aged ,Prognosis ,medicine.disease ,Debulking ,Surgery ,Lymphoma ,Survival Rate ,Female ,Immunoglobulin Light Chains ,business - Abstract
Summary Background Localised immunoglobulin light-chain amyloidosis, involving one type of tissue, is rare. Little systematic data exists regarding clinical presentations, course or outcomes, or risk of progression to systemic amyloidosis. We aimed to report clinical features and outcomes of a large series of patients with localised light-chain amyloidosis. Methods We examined data for all patients with localised amyloidosis who were diagnosed, assessed, and followed at the UK National Amyloidosis Centre (NAC) between Jan 2, 1980, and Dec 15, 2011, from the NAC database and written records. The inclusion criteria was the presence of biopsy sample proven localised amyloidosis classified as biopsy proven amyloid deposition confined to one site or tissue proven by histology of the tissue examined), without any evidence of vital organ involvement, which was defined as cardiac, renal, or liver involvement or peripheral or autonomic neuropathy and treatment naive. Findings We identified 606 patients with biopsy proven localised amyloidosis (likely light-chain type in 98%) from 5050 newly diagnosed patients with all types of amyloidosis. Median age was 59·5 years (IQR 50·2–74·5). The most common sites included bladder (95; 16%), laryngeal or tonsillar (92; 15%), cutaneous (84; 14%), and pulmonary nodular (47; 8%). 121 (20%) had a monoclonal immunoglobulin or abnormal circulating free light chains. At median follow-up of 74·4 months (IQR 37·2–132·0), seven (1%) patients progressed to systemic immunoglobin light-chain amyloidosis. 270 (51%) patients had one repeated treatment intervention and 112 (21%) had more than one repeated treatment interventions (predominantly localised debulking). The estimated 5-year overall survival was 90·6% (95% CI 87·7–92·9) and 10-year overall survival was 80·3% (75·1–84·1). In patients aged 70 years or older, median overall survival was 12·1 years (95% CI 10·5–13·7). Interpretation Localised immunoglobulin light-chain amyloidosis has an excellent prognosis with no apparent effect on life expectancy. Evolution into systemic immunoglobulin light chain amyloidosis is very rare. Funding None.
- Published
- 2015
22. Ixazomib, lenalidomide and dexamethasone in relapsed AL amyloidosis – a first report
- Author
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Rakesh Popat, Cristina Quarta, Charalampia Kyriakou, Oliver C Cohen, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Carol J. Whelan, Neil Rabin, Simon Cheesman, Raakhee Shah, Marianna Fontana, Helen J. Lachmann, Kwee Yong, Ana Martinez-Naharro, Shameem Mahmood, Julian D. Gillmore, Faye Sharpley, and Philip N. Hawkins
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Ixazomib ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,AL amyloidosis ,business ,Dexamethasone ,Lenalidomide ,medicine.drug - Published
- 2019
23. Structure, Folding Dynamics, and Amyloidogenesis of D76N β2-Microglobulin
- Author
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Mark B. Pepys, Young-Ho Lee, Sofia Giorgetti, Palma Mangione, Alessandra Corazza, Ranieri Rolandi, Vittorio Bellotti, Graham W. Taylor, Julian D. Gillmore, Monica Stoppini, Fabrizio Chiti, Philip N. Hawkins, Riccardo Porcari, Annalisa Relini, Sara Raimondi, Hisashi Yagi, Amanda Penco, Gennaro Esposito, Federico Fogolari, Yuji Goto, Mohsin M. Naqvi, and Ciro Cecconi
- Subjects
Globular protein ,macromolecular substances ,Protein aggregation ,010402 general chemistry ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,medicine ,Amyloid precursor protein ,Molecular Biology ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,Chemistry ,Amyloidosis ,P3 peptide ,Fibrillogenesis ,Cell Biology ,medicine.disease ,3. Good health ,0104 chemical sciences ,Biochemistry of Alzheimer's disease ,Cell biology ,biology.protein ,Protein folding - Abstract
Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin (β2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition.
- Published
- 2013
24. T1 Mapping for Myocardial Extracellular Volume Measurement by CMR
- Author
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Stefan K. Piechnik, James C. Moon, Philip N. Hawkins, Daniel Sado, Steven K White, Amir M. Sheikh, Andrew S. Flett, Matthew D. Robson, Marianna Fontana, Derek J. Hausenloy, Viviana Maestrini, and Sanjay M Banypersad
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cardiomyopathy ,Hypertrophic cardiomyopathy ,Infarction ,Magnetic resonance imaging ,Blood flow ,medicine.disease ,Bolus (medicine) ,Radiology Nuclear Medicine and imaging ,Internal medicine ,Heart failure ,Extracellular fluid ,medicine ,Cardiology ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives The aim of this study was to determine the accuracy of the contrast “bolus only” T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume fraction (ECV). Background Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR [EQ-CMR]) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. Methods One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. Results The ECV by both techniques correlated with histological CVF (n = 18, r 2 = 0.69, p 2 = 0.71, p 2 = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV 0.4 = 0.040 ± 0.075, p Conclusions Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.
- Published
- 2013
25. The electrocardiographic features associated with cardiac amyloidosis of variant transthyretin isoleucine 122 type in Afro-Caribbean patients
- Author
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Jason Dungu, Dorota Rowczenio, Jennifer H. Pinney, Julian D. Gillmore, Lisa J. Anderson, Prayman T. Sattianayagam, Philip N. Hawkins, Simon D. J. Gibbs, Sanjay M Banypersad, Janet A. Gilbertson, Ashutosh D. Wechalekar, Helen J. Lachmann, and Carol J. Whelan
- Subjects
Male ,medicine.medical_specialty ,Heart block ,Black People ,Left ventricular hypertrophy ,Electrocardiography ,Internal medicine ,medicine ,Humans ,Prealbumin ,cardiovascular diseases ,Aged ,Aged, 80 and over ,Bundle branch block ,medicine.diagnostic_test ,biology ,business.industry ,Amyloidosis ,Middle Aged ,medicine.disease ,Transthyretin ,Caribbean Region ,Cardiac amyloidosis ,Heart failure ,Cardiology ,biology.protein ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date.Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size.We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen (P.05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing.Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.
- Published
- 2012
26. Clinical Profiles and Outcomes in 1203 Newly Diagnosed Patients With Systemic AL Amyloidosis – First Analysis of the ALChemy Study
- Author
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Shameem Mahmood, Philip N. Hawkins, Sajitha Sachchithanantham, Julian D. Gillmore, Taryn Youngstein, Cristina Quarta, Helen J. Lachmann, Richa Manwani, Tamer Rezk, Darren Foard, Thirusha Lane, Ashutosh D. Wechalekar, Marianna Fontana, and Carol J. Whelan
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,AL amyloidosis ,Medicine ,Hematology ,Newly diagnosed ,business ,medicine.disease ,Dermatology ,Surgery - Published
- 2017
27. A case series and systematic literature review of anakinra and immunosuppression in idiopathic recurrent pericarditis
- Author
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Ian C. Scott, Helen J. Lachmann, Philip N. Hawkins, and Vijay Hajela
- Subjects
Anakinra ,medicine.medical_specialty ,Pediatrics ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,Autoinflammatory ,Azathioprine ,Immunosuppression ,Article ,Clinical trial ,Systematic review ,Refractory ,Internal medicine ,Immunology ,medicine ,Etiology ,Cardiology ,Recurrent pericarditis ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
SummaryIdiopathic recurrent pericarditis (IRP) impairs quality of life. Although its precise etiology is not certain, it is believed to be immunologically mediated. Its optimal treatments are unknown. Initial therapy is with non-steroidal anti-inflammatory drugs and colchicine. Steroids, which are often used, however may promote recurrences. European guidelines advocate azathioprine or cyclophosphamide in refractory cases despite limited evidence. We report two adults with IRP successfully treated with the interleukin-1 antagonist, anakinra. We combine this experience with the first systematic literature review of immunosuppression in IRP. A total of 8 papers were included in the review, which alongside our patients described 18 cases. The best treatments comprised anakinra and intravenous immunoglobulin, with respective remission rates of 100% and 67%. Cyclophosphamide and azathioprine were less efficacious. The unprovoked inflammatory episodes in our patients alongside their prompt response to anakinra indicate that in some instances IRP may represent an autoinflammatory condition. We suggest that in IRP refractory to initial treatment, anakinra should be considered as a potential therapy. Clinical trials are required to confirm its benefits in IRP.
- Published
- 2011
- Full Text
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28. Amyloidogenicity and Clinical Phenotype Associated with Five Novel Mutations in Apolipoprotein A-I
- Author
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Dorota Rowczenio, Helen J. Lachmann, Prayman T. Sattianayagam, Janet A. Gilbertson, Philip N. Hawkins, Ahmet Dogan, JH Pinney, Simon D. J. Gibbs, Ashutosh D. Wechalekar, Toby Hunt, Julie A. Vrana, Julian D. Gillmore, and Jason D. Theis
- Subjects
Adult ,Male ,Proteomics ,Amyloid ,Pathology ,medicine.medical_specialty ,Apolipoprotein B ,Biopsy ,DNA Mutational Analysis ,Fibril ,Pathology and Forensic Medicine ,Tandem Mass Spectrometry ,AL amyloidosis ,medicine ,Humans ,Radionuclide Imaging ,Serum amyloid P component ,Microdissection ,Aged ,Laser capture microdissection ,Apolipoprotein A-I ,biology ,Palate ,Lasers ,Amyloidosis ,Regular Article ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Serum Amyloid P-Component ,Phenotype ,Mutation ,biology.protein ,Female ,Mutant Proteins - Abstract
The phenotype of hereditary apolipoprotein A-I amyloidosis is heterogeneous with some patients developing extensive visceral amyloid deposits and end-stage renal failure as young adults and others having only laryngeal and/or skin amyloid, which may be of little clinical consequence. Clinical management and prognosis of patients with systemic amyloidosis depend entirely on correct identification of the fibril protein, such that light chain amyloidosis (AL, previously referred to as “primary”), the most frequently diagnosed type, is treated with chemotherapy, which has absolutely no role in hereditary apolipoprotein A-I amyloidosis. We report five novel apolipoprotein A-I variants, four of which were amyloidogenic and one of which was incidental in a patient with systemic AL amyloidosis. Interestingly, only one of four patients with apolipoprotein A-I amyloidosis had a family history of similar disease. Laser microdissection and tandem mass spectrometry–based proteomics were used to confirm the amyloid fibril protein and, for the first time in apolipoprotein A-I amyloidosis, demonstrated that only mutated protein as opposed to wild-type apolipoprotein A-I was deposited as amyloid. The clinical spectrum and outcome of hereditary apolipoprotein A-I amyloidosis are reviewed in detail and support the need for sequencing of the apolipoprotein A-I gene among patients with apparent localized amyloidosis in whom IHC is nondiagnostic of the fibril protein, even in the absence of a family history of disease.
- Published
- 2011
29. Differential cytokine secretion results from p65 and c-Rel NF-κB subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients
- Author
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Graham A. Hitman, Tom Pettersson, Michael F. McDermott, Margo Whiteford, Shane McKee, Peter D. Arkwright, Belinda Nedjai, Annamari Ranki, Susanna Stjernberg, Mark D. Turner, Philip N. Hawkins, Leigh D Church, and Kirsten Minden
- Subjects
Adult ,Male ,Fever ,medicine.medical_treatment ,Immunology ,Biology ,medicine.disease_cause ,Young Adult ,medicine ,Humans ,Secretion ,Child ,Transcription factor ,Immunoassay ,Mutation ,Hereditary Autoinflammatory Diseases ,Transcription Factor RelA ,Middle Aged ,medicine.disease ,Molecular biology ,Proto-Oncogene Proteins c-rel ,Cytokine ,Receptors, Tumor Necrosis Factor, Type I ,TNF receptor associated periodic syndrome ,Cancer research ,Cytokines ,Female ,Tumor necrosis factor alpha ,Cytokine secretion ,REL ,Signal Transduction - Abstract
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene which encodes the tumor necrosis factor (TNF) receptor, TNFR1. We investigated the effect of three high penetrance and three low penetrance TNFRSF1A mutations upon NF-κB transcription factor family subunit activity, and the resulting impact upon secretion of 25 different cytokines. Whilst certain mutations resulted in elevated NF-κB p65 subunit activity, others instead resulted in elevated c-Rel subunit activity. Interestingly, high p65 activity was associated with elevated IL-8 secretion, whereas high c-Rel activity increased IL-1β and IL-12 secretion. In conclusion, while all six TNFRSF1A mutations showed enhanced NF-κB activity, different mutations stimulated distinct NF-κB family subunit activities, and this in turn resulted in the generation of unique cytokine secretory profiles.
- Published
- 2011
30. Staging Cardiac Amyloidosis With CMR
- Author
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Ana Martinez-Naharro, Philip N. Hawkins, and Marianna Fontana
- Subjects
0106 biological sciences ,Pathology ,medicine.medical_specialty ,business.industry ,Amyloidosis ,MEDLINE ,030204 cardiovascular system & hematology ,medicine.disease ,01 natural sciences ,Phenotype ,03 medical and health sciences ,0302 clinical medicine ,Cardiac amyloidosis ,010608 biotechnology ,medicine ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,business - Published
- 2016
31. Reply
- Author
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Marianna Fontana, Tushar Kotecha, Philip N. Hawkins, Ana Martinez-Naharro, and Julian D. Gillmore
- Subjects
Pathology ,medicine.medical_specialty ,Mass spectrometry based proteomics ,medicine.diagnostic_test ,Amyloid ,business.industry ,Amyloidosis ,Myocardial edema ,Magnetic resonance imaging ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Edema ,medicine ,In patient ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
We thank Dr. Cao for his interest in our paper [(1)][1]. The aim of our study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. We propose that edema, detected using cardiovascular magnetic resonance, is an additional mechanism by which amyloid
- Published
- 2018
32. Solid Organ Transplantation in AL Amyloidosis
- Author
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Julian D. Gillmore, Philip N. Hawkins, JH Pinney, Carol J. Whelan, Sdj Gibbs, Helen J. Lachmann, Prayman T. Sattianayagam, Janet A. Gilbertson, and Ashutosh D. Wechalekar
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Liver transplantation ,Recurrence ,medicine ,AL amyloidosis ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Kidney transplantation ,Aged ,Heart transplantation ,Transplantation ,business.industry ,Amyloidosis ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Liver Transplantation ,Surgery ,Death, Sudden, Cardiac ,Treatment Outcome ,surgical procedures, operative ,Cardiac amyloidosis ,Feasibility Studies ,Heart Transplantation ,business ,Stem Cell Transplantation ,Primary systemic amyloidosis - Abstract
Vital organ failure remains common in AL amyloidosis. Solid organ transplantation is contentious because of the multisystem nature of this disease and risk of recurrence in the graft. We report outcome among all AL patients evaluated at the UK National Amyloidosis Centre who received solid organ transplants between 1984 and 2009. Renal, cardiac and liver transplants were performed in 22, 14 and 9 patients respectively, representing
- Published
- 2010
33. Organ Transplantation in Hereditary Apolipoprotein AI Amyloidosis
- Author
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Mark B. Pepys, Helen J. Lachmann, Dorota Rowczenio, John O'Grady, Julian D. Gillmore, Hugh J. B. Goodman, Glenys A. Tennent, Ashutosh D. Wechalekar, A Bybee, Nigel Heaton, Philip N. Hawkins, Janet A. Gilbertson, J. Acheson, and Arie J. Stangou
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Liver transplantation ,Organ transplantation ,Renal amyloidosis ,Amyloid disease ,Risk Factors ,Secondary Prevention ,medicine ,AL amyloidosis ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Kidney transplantation ,Retrospective Studies ,Transplantation ,Apolipoprotein A-I ,business.industry ,Amyloidosis ,Graft Survival ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Liver Transplantation ,Surgery ,Treatment Outcome ,surgical procedures, operative ,Mutation ,Kidney Failure, Chronic ,Female ,business ,Amyloidosis, Familial ,Liver Failure ,Follow-Up Studies - Abstract
Patients with hereditary apolipoprotein AI (apoAI) amyloidosis often have extensive visceral amyloid deposits, and many develop end-stage renal failure as young adults. Solid organ transplantation to replace failing organ function in systemic amyloidosis is controversial due to the multisystem and progressive nature of the disease and the risk of recurrence of amyloid in the graft. We report the outcome of solid organ transplantation, including dual transplants in 4 cases, among 10 patients with apoAI amyloidosis who were followed for a median (range) of 16 (4-28) and 9 (0.2-27) years from diagnosis of amyloidosis and transplantation, respectively. Eight of 10 patients were alive, seven with a functioning graft at censor. Two patients died, one of disseminated cytomegalovirus infection 2 months after renal transplantation and the other of multisystem failure following severe trauma more than 13 years after renal transplantation. The renal transplant of one patient failed due to recurrence of amyloid after 25 years. Amyloid disease progression was very slow and the natural history of the condition was favorably altered in both cases in which the liver was transplanted. Failing organs in hereditary apoAI amyloidosis should be replaced since graft survival is excellent and confers substantial survival benefit.
- Published
- 2006
34. Systemic amyloidosis
- Author
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Helen J, Lachmann and Philip N, Hawkins
- Subjects
Survival Rate ,Pharmacology ,Anti-Inflammatory Agents, Non-Steroidal ,Drug Discovery ,Humans ,Amyloidosis ,Prognosis - Abstract
Amyloidosis describes a heterogeneous group of diseases in which normally soluble plasma proteins are deposited in the extracellular space in an abnormal insoluble fibrillar form. These diseases can affect virtually any organ system and often present a major diagnostic and management challenge. Current therapies centre on reducing the supply of the respective amyloid fibril precursor protein, combined with supportive treatment. Better understanding of the mechanisms underlying amyloid formation has led to the development of novel treatment strategies aimed at inhibiting fibrillogenesis or destabilizing existing amyloid deposits. It is hoped that some of these developments might contribute to effective treatment not only of systemic amyloidosis, which is relatively rare, but also of the much more common type II diabetes and Alzheimer's disease, in which local amyloid formation is thought to play a role.
- Published
- 2006
35. NALP3 Forms an IL-1β-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder
- Author
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Fabio Martinon, Kimberly Burns, Philip N. Hawkins, Michael F. McDermott, Laetitia Agostini, and Jürg Tschopp
- Subjects
Macromolecular Substances ,Immunology ,NALP3 ,Autoimmune Diseases ,Cell Line ,Familial Cold Autoinflammatory Syndrome ,NLRC4 ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Humans ,Immunology and Allergy ,Protein Precursors ,NALP ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Inflammation ,biology ,Macrophages ,Caspase 1 ,Cryopyrin-associated periodic syndrome ,Inflammasome ,medicine.disease ,Neoplasm Proteins ,Protein Structure, Tertiary ,CARD Signaling Adaptor Proteins ,Cytoskeletal Proteins ,Infectious Diseases ,Mutation ,biology.protein ,Carrier Proteins ,NLRP3 inflammasome complex ,Inflammasome complex ,Interleukin-1 ,medicine.drug - Abstract
Mutations within the NALP3/cryopyrin/CIAS1 gene are responsible for three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. The NALP3 protein is homologous to NALP1, which is a component of the inflammasome, a molecular platform that activates the proinflammatory caspases-1 and -5. NALP3 (and other members of the NALP family) lacks the C-terminal, CARD-containing sequence of NALP1, and its role in caspase activation is unclear. Here, we report that NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity. Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders.
- Published
- 2004
- Full Text
- View/download PDF
36. Length of Hospital Stay is an Independent Predictor of Overall Survival in Patients with systemic AL Amyloidosis
- Author
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Ashutosh D. Wechalekar, Carol J. Whelan, Marianna Fontana, Helen J. Lachmann, Shameem Mahmood, Philip N. Hawkins, Cristina Quarta, Ahmed Mohamed Abdel Shafì, and Julian D. Gillmore
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Independent predictor ,Oncology ,Emergency medicine ,medicine ,Overall survival ,AL amyloidosis ,In patient ,Intensive care medicine ,business ,Hospital stay - Published
- 2017
37. Tolérance et efficacité à long terme du canakinumab dans les CAPS : Résultats du Registre ß-Confident
- Author
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Philip N. Hawkins, V.D.P. Tom, Isabelle Koné-Paut, A. Speziale, H. Hoffman, W. Ulrich, H.T. Hugh, J. B. Kuemmerle-Deschner, and Y. Joubert
- Subjects
Rheumatology - Published
- 2016
38. Comparison of usefulness between exercise capacity and echocardiographic indexes of left ventricular function in cardiac amyloidosis
- Author
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Celia M Oakley, Petros Nihoyannopoulos, Loukianos Rallidis, Athanasios G Trikas, and Philip N. Hawkins
- Subjects
Adult ,Male ,medicine.medical_specialty ,Heart disease ,Doppler echocardiography ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,Oxygen Consumption ,Internal medicine ,medicine ,Humans ,Heart Failure ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,VO2 max ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Cardiac amyloidosis ,Echocardiography ,Heart failure ,Exercise Test ,Cardiology ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,Anaerobic exercise ,Primary systemic amyloidosis - Abstract
In patients with primary systemic amyloidosis (AL), the echocardiographic assessment of ventricular function alone does not always correspond to patients' symptoms and functional status. Peak oxygen uptake and anaerobic threshold (AT), in contrast, constitute 2 objective, reliable and reproducible indicators of functional status in patients with circulatory failure. Thirty-two consecutive patients (mean age 50 +/- 13 years) with histologic evidence of systemic primary AL were studied (29 AL, 3 hereditary). There were 16 with echocardiographic features of cardiac infiltration (group I) and 16 without (group II). Twenty age- and gender-matched healthy subjects were also studied for comparison. Of the 32 patients, 12 were in New York Heart Association functional class I, 9 were in class II, and 11 were in class III. Each subject underwent 2-dimensional and Doppler echocardiography and cardiopulmonary exercise testing using a modified Bruce protocol. Left atrial (LA), left ventricular (LV) dimensions, wall thickness, and LV fractional shortening, as well as transmitral flow velocities and their E/A ratio were measured. Peak oxygen consumption (VO2max [ml/kg/min]), AT (ml/kg/min), and exercise duration (seconds) were also measured. VO2max and AT were lower in patients with AL than in controls (20.8 +/- 7.0 vs 35.0 +/- 8.5, p0.001 and 13.1 +/- 3.7 vs 27.0 +/- 4.2, p0.001, respectively). As a group, symptomatic patients had lower VO2max, AT, and exercise duration than those without symptoms (17.1 +/- 3.6 vs 27.0 +/- 6.9, p = 0.0001, 11.1 +/- 2.1 vs 16.2 +/- 3.6, p = 0.0001, and 489 +/- 235 vs 843 +/- 197, p = 0.0001, respectively), whereas LV dimensions only showed a small difference (p = 0.03). VO2max, AT, and exercise duration of patients in functional class I were higher than those in functional classes II and III (p = 0.01, p0.05, and p = 0.007, respectively). Asymptomatic patients had lower VO2max, AT, and exercise duration than controls (p0.0001). VO2max, AT, and exercise duration were poorly related to LA diameter, LV dimensions, fractional shortening, wall thickness, peak velocities of E and A waveforms, and E/A ratio. Patients with VO2max15 ml/kg/min had a better survival than patients with VO2max15 ml/kg/min. Thus, in patients with primary systemic AL, cardiorespiratory exercise testing is the preferred way of assessing functional capacity. Echocardiographic Doppler indexes at rest are not predictive of a patient's symptoms and exercise capacity. Furthermore, VO2max is a strong independent predictor of survival in these patients.
- Published
- 1999
39. Echocardiographic assessment of cardiac involvement in systemic AL amyloidosis in relation to whole body amyloid load measured by serum amyloid P component (SAP) clearance
- Author
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Gerald J. Clesham, Celia M. Oakley, Petros Nihoyannopoulos, Mark B. Pepys, Philip N. Hawkins, and D M Vigushin
- Subjects
Adult ,Male ,Amyloid ,medicine.medical_specialty ,Pathology ,Time Factors ,Heart disease ,Heart Ventricles ,Hemodynamics ,Ventricular Function, Left ,Iodine Radioisotopes ,Internal medicine ,medicine ,AL amyloidosis ,Humans ,Serum amyloid P component ,Aged ,biology ,business.industry ,Amyloidosis ,Middle Aged ,medicine.disease ,Echocardiography, Doppler ,Transplantation ,Serum Amyloid P-Component ,Cardiac amyloidosis ,cardiovascular system ,Cardiology ,biology.protein ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business - Abstract
Using SAP tracer studies we have shown here, for the first time in vivo, that the severity of cardiac AL amyloidosis is unrelated to the whole body amyloid load. Measurements of radiolabeled SAP clearance would thus enable identification of patients with cardiac amyloidosis in whom systemic involvement is limited and who might therefore be the best candidates for cardiac transplantation.
- Published
- 1997
40. Long-term survival in systemic amyloid A amyloidosis complicating Crohn's disease
- Author
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Mark B. Pepys, Laurence Lovat, S Madhoo, and Philip N. Hawkins
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Adolescent ,Amyloid ,Iodine Radioisotopes ,Crohn Disease ,AA amyloidosis ,Humans ,Medicine ,Serum amyloid A ,Child ,Radionuclide Imaging ,Serum amyloid P component ,Serum Amyloid A Protein ,Crohn's disease ,Hepatology ,biology ,business.industry ,Amyloidosis ,Gastroenterology ,medicine.disease ,Survival Analysis ,Transplantation ,Serum Amyloid P-Component ,biology.protein ,Kidney Failure, Chronic ,Female ,business ,Kidney disease - Abstract
Systemic AA amyloidosis is a serious and potentially fatal complication of Crohn's disease. Proteinuria is the most common presentation, but the diagnosis can only be confirmed by showing amyloid in the tissues and is often delayed. Recently, scintigraphy has been developed using 123I-serum amyloid P component (SAP) as a noninvasive and quantitative alternative to histology in which this nuclear medicine tracer specifically targets amyloid deposits in vivo. This study investigates 4 patients with Crohn's disease who, despite having only low-grade clinical activity, developed progressive AA amyloidosis and renal failure. One patient died while receiving hemodialysis, but in the other 3 cases, renal transplantation and standard antirejection therapy were associated with remission of inflammatory activity. Serial SAP scintigraphy showed regression of amyloid in 2 of these patients and absence of progression in the other. These case studies show the dynamic but variable behavior of AA deposits in different patients and show the use of radiolabeled SAP for diagnosis and monitoring of amyloidosis in Crohn's disease.
- Published
- 1997
41. SYSTEMATIC REVIEW OF 1142 ADMISSIONS WITH ACUTE HEART FAILURE REVEALS HIGH FREQUENCY OF TRANSTHYRETIN V122I CARDIAC AMYLOIDOSIS IN AFRO-CARIBBEAN PATIENTS
- Author
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Jason Dungu, Mark S. O'Donnell, Lisa J. Anderson, and Philip N. Hawkins
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Afro-Caribbean ,medicine.disease ,Transthyretin ,Cardiac amyloidosis ,Internal medicine ,Heart failure ,medicine ,Cardiology ,biology.protein ,business ,Cardiology and Cardiovascular Medicine - Published
- 2012
- Full Text
- View/download PDF
42. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis
- Author
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Ole B. Suhr, B.G Wallin, S Richardson, Gösta Holmgren, Philip N. Hawkins, Mark B. Pepys, A Seymour, Lars Steen, Carl-Gustav Groth, Oluf Andersen, and B.-G Ericzon
- Subjects
Adult ,Male ,Tafamidis ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Liver transplantation ,chemistry.chemical_compound ,medicine ,Humans ,Prealbumin ,Serum amyloid P component ,biology ,business.industry ,Amyloidosis ,Peripheral Nervous System Diseases ,General Medicine ,Middle Aged ,medicine.disease ,Liver Transplantation ,Transplantation ,Transthyretin ,Amyloid Neuropathy ,Peripheral neuropathy ,chemistry ,biology.protein ,business - Abstract
Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.
- Published
- 1993
43. Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component
- Author
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Christopher G. Winearls, Philip N. Hawkins, P.E. Gower, Christopher W. Pugh, Nelson, D. O. Oliver, Mark B. Pepys, D. Sethi, S Richardson, and J. P. Lavender
- Subjects
Pathology ,medicine.medical_specialty ,Time Factors ,Amyloid ,medicine.medical_treatment ,Scintigraphy ,Iodine Radioisotopes ,Amyloid disease ,Renal Dialysis ,medicine ,Humans ,Prospective Studies ,Radionuclide Imaging ,Serum amyloid P component ,Dialysis ,medicine.diagnostic_test ,biology ,business.industry ,Amyloidosis ,General Medicine ,medicine.disease ,Serum Amyloid P-Component ,Injections, Intravenous ,biology.protein ,Kidney Failure, Chronic ,Haemodialysis-associated amyloidosis ,Hemodialysis ,Joint Diseases ,business - Abstract
Long-term haemodialysis is frequently complicated by amyloid deposition in which the fibrils consist of beta 2-microglobulin. Dialysis-related amyloid disease causes extensive morbidity and has been associated with deaths in some cases. All amyloid deposits contain amyloid P component that is derived from the normal circulating protein, serum amyloid P component (SAP). We have used scintigraphic imaging after injection of 123I-labelled SAP to assess the distribution of amyloidosis in 38 patients receiving long-term haemodialysis for end-stage renal failure. There was focal localisation of tracer at all sites where histological examination confirmed amyloid deposition. Splenic uptake was seen in 12 patients, indicating splenic amyloidosis, but there was no evidence of other visceral involvement. 6 control subjects who had been dialysed for under 1.5 years showed no localisation of tracer, nor was there any uptake of 123I-labelled human serum albumin in 3 long-term dialysis patients with histologically confirmed amyloidosis and positive 123I-SAP images. Negative scans were also obtained in 5 patients who had been transplanted 0.8-2.4 years previously, despite past evidence of dialysis arthropathy (5) and histologically proven amyloidosis (4). 123I-SAP scintigraphy may be helpful as a non-invasive method for both the diagnosis and monitoring of dialysis-associated amyloidosis.
- Published
- 1991
44. Interim analysis of ALCHemy – a prospective study of 1000 patients with Systemic AL amyloidosis
- Author
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Taryn Youngstein, Shameem Mahmood, Philip N. Hawkins, A.D. Wechalekar, Darren Foard, Julian D. Gillmore, Helen J. Lachmann, Mark R.E. Coyne, Ashutosh D. Wechalekar, M Fontana, Carol J. Whelan, and Thirusha Lane
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,General surgery ,medicine ,AL amyloidosis ,Hematology ,medicine.disease ,Interim analysis ,Prospective cohort study ,business ,Surgery - Published
- 2015
45. Heavy/light chain immunoparesis identifies systemic AL amyloidosis patients with poor survival outcomes
- Author
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O. Berlanga, A. Alvi, Sajitha Sachchithanantham, Julian D. Gillmore, NJ Wassef, R Sayeed, Helen J. Lachmann, Shameem Mahmood, Ashutosh D. Wechalekar, Philip N. Hawkins, and Carol J. Whelan
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Family medicine ,Amyloidosis ,medicine ,Medical school ,AL amyloidosis ,Hematology ,medicine.disease ,business - Abstract
e192 PO-193 Heavy/light chain immunoparesis identifies systemic AL amyloidosis patients with poor survival outcomes S. Sachchithanantham, O. Berlanga, A. Alvi, N. Wassef, S. Mahmood, R. Sayeed, J. Gillmore, H. Lachmann, C. Whelan, P. Hawkins, A. Wechalekar National Amyloidosis Centre, University College London Medical School, London, UK; The Binding Ste Group Ltd, Birmingham, UK; Department of Biochemistry, Royal Free London NHS Foundation trust, London, UK
- Published
- 2015
46. Bleeding diathesis and prothrombotic tendencies in patients with newly diagnosed systemic light chain Amyloidosis: important clinical implications
- Author
-
Ashutosh D. Wechalekar, Cristina Quarta, Carol J. Whelan, Ketna Patel, K. Gomez, Mark R.E. Coyne, Julian D. Gillmore, Sajitha Sachchithanantham, Rabya Sayed, Taryn Youngstein, Helen J. Lachmann, Thirusha Lane, Darren Foard, Shameem Mahmood, Philip N. Hawkins, A. Riddle, and Marianna Fontanna
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,General surgery ,Amyloidosis ,education ,Medical school ,Hematology ,Newly diagnosed ,medicine.disease ,Haemophilia ,Surgery ,Bleeding diathesis ,Oncology ,medicine ,In patient ,business - Abstract
PO-206 Bleeding diathesis and prothrombotic tendencies in patients with newly diagnosed systemic light chain Amyloidosis: important clinical implications S. Mahmood, A. Riddle, S. Sachchithanantham, T. Lane, D. Foard, T. Youngstein, R. Sayed, K. Patel, M. Fontanna, M. Coyne, C. Quarta, C.J. Whelan, H.J. Lachmann, J.D. Gillmore, P.N. Hawkins, K. Gomez, A.D. Wechalekar Division of Medicine, Royal Free Hospital Campus, National Amyloidosis Centre, University College of London Medical School, London, United Kingdom; Haemophilia Department, Royal Free Hospital, Rowland Street, London, United Kingdom
- Published
- 2015
47. B081 Hevylite™ Detects Residual IgGK in IgG Heavy-chain Disease
- Author
-
Philip N. Hawkins, Helen J. Lachmann, C Margetts, Arthur R. Bradwell, Graham P. Mead, and Stephen Harding
- Subjects
Cancer Research ,Oncology ,business.industry ,Immunology ,Medicine ,Hematology ,General Medicine ,IGG HEAVY CHAIN DISEASE ,business ,Residual - Published
- 2009
48. DIFFERENTIATING HYPERTENSIVE HEART DISEASE AND CARDIAC TRANSTHYRETIN ISOLEUCINE 122 (V122I) AMYLOIDOSIS IN AFRO-CARIBBEAN PATIENTS
- Author
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Philip N. Hawkins, Lisa J. Anderson, Oswaldo Valencia, Aigul Baltabaeva, Jason Dungu, and Tarek Ft Antonios
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Amyloidosis ,Afro-Caribbean ,medicine.disease ,Gastroenterology ,Hypertensive heart disease ,Transthyretin ,Endocrinology ,Internal medicine ,biology.protein ,medicine ,Isoleucine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2012
49. Efficacy and Safety of Canakinumab in a Large Cohort of Cryopyrin-Associated Periodic Syndrome (CAPS) Patients across All Severity Phenotypes
- Author
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N Patel, R Preiss, Philip N. Hawkins, Pierre Quartier, J Hoyer, A Widmer, Marco Gattorno, R Cartwright, Isabelle Koné-Paut, Kieron S. Leslie, Eric Hachulla, Judith A. Smith, and J. B. Kuemmerle-Deschner
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Cryopyrin-associated periodic syndrome ,medicine.disease ,Phenotype ,Large cohort ,Canakinumab ,Internal medicine ,Physical therapy ,Immunology and Allergy ,Medicine ,business ,medicine.drug - Published
- 2011
50. DETERMINING THE ELECTROCARDIOGRAPHIC FEATURES SPECIFIC TO TRANSTHYRETIN CARDIAC AMYLOID
- Author
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Lisa J. Anderson, Philip N. Hawkins, Jason Dungu, and Prayman T. Sattianayagam
- Subjects
Pathology ,medicine.medical_specialty ,Transthyretin ,Amyloid ,biology ,business.industry ,medicine ,biology.protein ,Cardiology and Cardiovascular Medicine ,business - Published
- 2010
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