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Silvia Castelletti

Bio: Silvia Castelletti is an academic researcher from University College London. The author has contributed to research in topics: Medicine & Cardiology. The author has an hindex of 21, co-authored 71 publications receiving 1510 citations. Previous affiliations of Silvia Castelletti include St Bartholomew's Hospital & University of Pavia.

Papers published on a yearly basis

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Journal ArticleDOI
TL;DR: Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloids, but with lower maximal T1 elevation, and appears to be an early disease marker.
Abstract: Objectives The aims of the study were to explore the ability of native myocardial T1 mapping by cardiac magnetic resonance to: 1) detect cardiac involvement in patients with transthyretin amyloidosis (ATTR amyloidosis); 2) track the cardiac amyloid burden; and 3) detect early disease. Background ATTR amyloidosis is an underdiagnosed cause of heart failure, with no truly quantitative test. In cardiac immunoglobulin light-chain amyloidosis (AL amyloidosis), T1 has high diagnostic accuracy and tracks disease. Here, the diagnostic role of native T1 mapping in the other key type of cardiac amyloid, ATTR amyloidosis, is assessed. Methods A total of 3 groups were studied: ATTR amyloid patients (n = 85; 70 males, age 73 ± 10 years); healthy individuals with transthyretin mutations in whom standard cardiac investigations were normal (n = 8; 3 males, age 47 ± 6 years); and AL amyloid patients (n = 79; 55 males, age 62 ± 10 years). These were compared with 52 healthy volunteers and 46 patients with hypertrophic cardiomyopathy (HCM). All underwent T1 mapping (shortened modified look-locker inversion recovery); ATTR patients and mutation carriers also underwent cardiac 3,3-diphosphono-1,2-propanodicarboxylicacid (DPD) scintigraphy. Results T1 was elevated in ATTR patients compared with HCM and normal subjects (1,097 ± 43 ms vs. 1,026 ± 64 ms vs. 967 ± 34 ms, respectively; both p Conclusions Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloid, but with lower maximal T1 elevation, and appears to be an early disease marker.

339 citations

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TL;DR: In this paper, the authors explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance.
Abstract: Background— Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance. Methods and Results— A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and 99mTC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69–85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5–35.8]; P =0.001). Conclusions— Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.

198 citations

Journal ArticleDOI
TL;DR: The spectrum and prevalence of mutations in the 12 Brugada syndrome (BrS)-susceptibility genes discovered to date in a single large cohort of unrelated BrS patients were provided to date and putative pathogenic mutations were identified.

190 citations

Journal ArticleDOI
TL;DR: Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.
Abstract: Objectives The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood. Background ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement—a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic. Methods Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct. Results Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R2 = 0.51; p Conclusions Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

125 citations

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TL;DR: In this paper, the authors defined reference values of cardiac volumes, dimensions, and new morpho-functional parameters normalized for age, gender, and body surface area by cine-bSSFP (balanced steady-state free-precession) magnetic resonance (MR).
Abstract: Purpose To define reference values of cardiac volumes, dimensions, and new morpho-functional parameters normalized for age, gender, and body surface area by cine-bSSFP (balanced steady-state free-precession) magnetic resonance (MR). Materials and Methods We enrolled 308 healthy subjects subdivided by gender and by six age classes: class I, >15–20 years; class II, >20–30 years; class III, >30–40 years; class IV, >40–50 years; class V, >50–60 years; and class VI >60 years. Dimensional, volumetric and morpho-functional parameters of the left (LV) and right (RV) ventricles were measured using cine-bSSFP MRI at 1.5T. Results The LV and RV end-diastolic volume indexes (EDVi) were inversely related to age (P < 0.0001 r = –0.34 and P < 0.0001 r = –0.37, respectively). In addition, the LV mass index decreased with age (P = 0.0004, r = –0.21). The LV longitudinal shortening was not significantly different among groups: ≥15% in all populations (95% confidence interval [CI]: 16–31). The sphericity index measured in end-diastole was higher in females than in males (P < 0.03): the upper limit was 40% for males and 42% for females. The normality cutoff of LV global function index was ≥33% in males and ≥35% in females. The end-diastolic volume (EDV) of RV and LV was balanced (RV/LV ratio 0.85–1.15) without differences in the population. The LV EDV/mass was 1.0–1.8 in males and 1.0–2.1 in females. Conclusion This study provides potential age- and gender-specific reference. Evidence level 2 J. Magn. Reson. Imaging 2016.

78 citations


Cited by
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TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)

13,400 citations

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TL;DR: The panel of experts, having emphasised the importance of initiating aetiologic treatment for any degree of hepatic disease at the earliest possible stage, extended its work to all the complications of cirrhosis which had not been covered by the European Association for the Study of the Liver guidelines.

1,534 citations

Journal ArticleDOI
TL;DR: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy, and proposes noninvasive diagnostic criteria that are applicable to the majority of patients with this disease.
Abstract: Background—Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed...

1,185 citations