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Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years

Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. METHODS: This is a retrospective observational cohort study of...

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Autores principales: Ioannou, Adam, Patel, Rishi K., Razvi, Yousuf, Porcari, Aldostefano, Sinagra, Gianfranco, Venneri, Lucia, Bandera, Francesco, Masi, Ambra, Williams, Georgina E., O’Beara, Sophie, Ganesananthan, Sharmananthan, Massa, Paolo, Knight, Daniel, Martinez-Naharro, Ana, Kotecha, Tushar, Chacko, Liza, Brown, James, Rauf, Muhammad U., Manisty, Charlotte, Moon, James, Lachmann, Helen, Wechelakar, Ashutosh, Petrie, Aviva, Whelan, Carol, Hawkins, Philip N., Gillmore, Julian D., Fontana, Marianna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698091/
https://www.ncbi.nlm.nih.gov/pubmed/36325894
http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060852
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author Ioannou, Adam
Patel, Rishi K.
Razvi, Yousuf
Porcari, Aldostefano
Sinagra, Gianfranco
Venneri, Lucia
Bandera, Francesco
Masi, Ambra
Williams, Georgina E.
O’Beara, Sophie
Ganesananthan, Sharmananthan
Massa, Paolo
Knight, Daniel
Martinez-Naharro, Ana
Kotecha, Tushar
Chacko, Liza
Brown, James
Rauf, Muhammad U.
Manisty, Charlotte
Moon, James
Lachmann, Helen
Wechelakar, Ashutosh
Petrie, Aviva
Whelan, Carol
Hawkins, Philip N.
Gillmore, Julian D.
Fontana, Marianna
author_facet Ioannou, Adam
Patel, Rishi K.
Razvi, Yousuf
Porcari, Aldostefano
Sinagra, Gianfranco
Venneri, Lucia
Bandera, Francesco
Masi, Ambra
Williams, Georgina E.
O’Beara, Sophie
Ganesananthan, Sharmananthan
Massa, Paolo
Knight, Daniel
Martinez-Naharro, Ana
Kotecha, Tushar
Chacko, Liza
Brown, James
Rauf, Muhammad U.
Manisty, Charlotte
Moon, James
Lachmann, Helen
Wechelakar, Ashutosh
Petrie, Aviva
Whelan, Carol
Hawkins, Philip N.
Gillmore, Julian D.
Fontana, Marianna
author_sort Ioannou, Adam
collection PubMed
description Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. METHODS: This is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002–2021) in whom ATTR-CA was a differential diagnosis. RESULTS: We identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P<0.001). This was accompanied by a greater number of ATTR-CA diagnoses, predominantly of the wild-type nonhereditary form, which is now the most commonly diagnosed form of ATTR-CA (0% versus 54% versus 67% versus 66%, chi-square P<0.001). Over time, the median duration of associated symptoms before diagnosis fell from 36 months between 2002 and 2006 to 12 months between 2017 and 2021 (Mann–Whitney P<0.001), and a greater proportion of patients had early-stage disease at diagnosis across the 5-year periods (National Amyloidosis Centre stage 1: 34% versus 42% versus 44% versus 53%, chi-square P<0.001). This was associated with more favorable echocardiographic parameters of structure and function, including lesser interventricular septal thickness (18.0±3.8 mm versus 17.2±2.6 mm versus 16.9±2.3 mm versus 16.6±2.4 mm, P=0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P<0.001). Mortality decreased progressively during the study period (2007–2011 versus 2012–2016: hazard ratio, 1.57 [95% CI, 1.31–1.89], P<0.001; and 2012–2016 versus 2017–2021: hazard ratio, 1.89 [95% CI, 1.55–2.30], P<0.001). The proportion of patients enrolled into clinical trials and prescribed disease-modifying therapy increased over the 20-year period, but even when censoring at the trial or medication start date, year of diagnosis remained a significant predictor of mortality (2012–2016 versus 2017–2021: hazard ratio, 1.05 [95% CI, 1.03–1.07], P<0.001). CONCLUSIONS: There has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.
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spelling pubmed-96980912022-11-28 Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years Ioannou, Adam Patel, Rishi K. Razvi, Yousuf Porcari, Aldostefano Sinagra, Gianfranco Venneri, Lucia Bandera, Francesco Masi, Ambra Williams, Georgina E. O’Beara, Sophie Ganesananthan, Sharmananthan Massa, Paolo Knight, Daniel Martinez-Naharro, Ana Kotecha, Tushar Chacko, Liza Brown, James Rauf, Muhammad U. Manisty, Charlotte Moon, James Lachmann, Helen Wechelakar, Ashutosh Petrie, Aviva Whelan, Carol Hawkins, Philip N. Gillmore, Julian D. Fontana, Marianna Circulation Original Research Articles Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. METHODS: This is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002–2021) in whom ATTR-CA was a differential diagnosis. RESULTS: We identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P<0.001). This was accompanied by a greater number of ATTR-CA diagnoses, predominantly of the wild-type nonhereditary form, which is now the most commonly diagnosed form of ATTR-CA (0% versus 54% versus 67% versus 66%, chi-square P<0.001). Over time, the median duration of associated symptoms before diagnosis fell from 36 months between 2002 and 2006 to 12 months between 2017 and 2021 (Mann–Whitney P<0.001), and a greater proportion of patients had early-stage disease at diagnosis across the 5-year periods (National Amyloidosis Centre stage 1: 34% versus 42% versus 44% versus 53%, chi-square P<0.001). This was associated with more favorable echocardiographic parameters of structure and function, including lesser interventricular septal thickness (18.0±3.8 mm versus 17.2±2.6 mm versus 16.9±2.3 mm versus 16.6±2.4 mm, P=0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P<0.001). Mortality decreased progressively during the study period (2007–2011 versus 2012–2016: hazard ratio, 1.57 [95% CI, 1.31–1.89], P<0.001; and 2012–2016 versus 2017–2021: hazard ratio, 1.89 [95% CI, 1.55–2.30], P<0.001). The proportion of patients enrolled into clinical trials and prescribed disease-modifying therapy increased over the 20-year period, but even when censoring at the trial or medication start date, year of diagnosis remained a significant predictor of mortality (2012–2016 versus 2017–2021: hazard ratio, 1.05 [95% CI, 1.03–1.07], P<0.001). CONCLUSIONS: There has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design. Lippincott Williams & Wilkins 2022-11-03 2022-11-29 /pmc/articles/PMC9698091/ /pubmed/36325894 http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060852 Text en © 2022 The Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
spellingShingle Original Research Articles
Ioannou, Adam
Patel, Rishi K.
Razvi, Yousuf
Porcari, Aldostefano
Sinagra, Gianfranco
Venneri, Lucia
Bandera, Francesco
Masi, Ambra
Williams, Georgina E.
O’Beara, Sophie
Ganesananthan, Sharmananthan
Massa, Paolo
Knight, Daniel
Martinez-Naharro, Ana
Kotecha, Tushar
Chacko, Liza
Brown, James
Rauf, Muhammad U.
Manisty, Charlotte
Moon, James
Lachmann, Helen
Wechelakar, Ashutosh
Petrie, Aviva
Whelan, Carol
Hawkins, Philip N.
Gillmore, Julian D.
Fontana, Marianna
Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title_full Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title_fullStr Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title_full_unstemmed Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title_short Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years
title_sort impact of earlier diagnosis in cardiac attr amyloidosis over the course of 20 years
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698091/
https://www.ncbi.nlm.nih.gov/pubmed/36325894
http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060852
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