Deep phenotyping of p.(V142I)-associated variant transthyretin amyloid cardiomyopathy : Distinct from wild-type transthyretin amyloidosis?
© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology..
AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. A total of 3-4% of individuals of African descent carry a TTR gene mutation encoding the p.(V142I) variant, a powerful risk factor for development of variant ATTR-CM (ATTRv-CM); this equates to 1.6 million carriers in the United States. We undertook deep phenotyping of p.(V142I)-ATTRv-CM and comparison with wild-type ATTR-CM (ATTRwt-CM).
METHODS AND RESULTS: A retrospective study of 413 patients with p.(V142I) ATTRv-CM who attended the UK National Amyloidosis Centre (NAC) was conducted. Patients underwent evaluation at time of diagnosis, including clinical, echocardiography, and biomarker analysis; a subgroup had cardiac magnetic resonance (CMR) imaging. A total of 413 patients with ATTRwt-CM, matched for independent predictors of prognosis (age, NAC Stage, decade of first presentation), were used as a comparator group. At time of diagnosis, patients with ATTRv-CM had significant functional impairment by New York Heart Association classification (NHYA class ≥ III; 38%) and 6-min walk test distance (median 276 m). Median 5-year survival in ATTRv-CM patients was 31 versus 59 months in matched patients with ATTRwt-CM (p < 0.001). Patients with ATTRv-CM had significant impairment of functional parameters by echocardiography including biventricular impairment, high burden of regurgitant valvular disease and low cardiac output. Multivariable analysis revealed the prognostic importance of right ventricular dysfunction. CMR and histological analysis revealed myocyte atrophy and widespread myocardial infiltration in ATTRv-CM.
CONCLUSION: p.(V142I)-ATTRv-CM has an aggressive phenotype characterized by myocyte loss and widespread myocardial infiltration which may account for frequent biventricular failure and poor prognosis in this ATTR-CM genotypic subgroup.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
|---|---|
| Enthalten in: |
European journal of heart failure - 26(2024), 2 vom: 11. Feb., Seite 383-393 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Razvi, Yousuf [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Amyloid |
|---|
| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/ejhf.3088 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36445380X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36445380X | ||
| 003 | DE-627 | ||
| 005 | 20240327235428.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ejhf.3088 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1350.xml |
| 035 | |a (DE-627)NLM36445380X | ||
| 035 | |a (NLM)37953725 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Razvi, Yousuf |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Deep phenotyping of p.(V142I)-associated variant transthyretin amyloid cardiomyopathy |b Distinct from wild-type transthyretin amyloidosis? |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.03.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. | ||
| 520 | |a AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. A total of 3-4% of individuals of African descent carry a TTR gene mutation encoding the p.(V142I) variant, a powerful risk factor for development of variant ATTR-CM (ATTRv-CM); this equates to 1.6 million carriers in the United States. We undertook deep phenotyping of p.(V142I)-ATTRv-CM and comparison with wild-type ATTR-CM (ATTRwt-CM) | ||
| 520 | |a METHODS AND RESULTS: A retrospective study of 413 patients with p.(V142I) ATTRv-CM who attended the UK National Amyloidosis Centre (NAC) was conducted. Patients underwent evaluation at time of diagnosis, including clinical, echocardiography, and biomarker analysis; a subgroup had cardiac magnetic resonance (CMR) imaging. A total of 413 patients with ATTRwt-CM, matched for independent predictors of prognosis (age, NAC Stage, decade of first presentation), were used as a comparator group. At time of diagnosis, patients with ATTRv-CM had significant functional impairment by New York Heart Association classification (NHYA class ≥ III; 38%) and 6-min walk test distance (median 276 m). Median 5-year survival in ATTRv-CM patients was 31 versus 59 months in matched patients with ATTRwt-CM (p < 0.001). Patients with ATTRv-CM had significant impairment of functional parameters by echocardiography including biventricular impairment, high burden of regurgitant valvular disease and low cardiac output. Multivariable analysis revealed the prognostic importance of right ventricular dysfunction. CMR and histological analysis revealed myocyte atrophy and widespread myocardial infiltration in ATTRv-CM | ||
| 520 | |a CONCLUSION: p.(V142I)-ATTRv-CM has an aggressive phenotype characterized by myocyte loss and widespread myocardial infiltration which may account for frequent biventricular failure and poor prognosis in this ATTR-CM genotypic subgroup | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amyloid | |
| 650 | 4 | |a Cardiomyopathy | |
| 650 | 4 | |a TTR | |
| 650 | 4 | |a Transthyretin | |
| 650 | 4 | |a V122I | |
| 650 | 7 | |a Prealbumin |2 NLM | |
| 700 | 1 | |a Ioannou, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Rishi K |e verfasserin |4 aut | |
| 700 | 1 | |a Chacko, Liza |e verfasserin |4 aut | |
| 700 | 1 | |a Karia, Nina |e verfasserin |4 aut | |
| 700 | 1 | |a Riefolo, Mattia |e verfasserin |4 aut | |
| 700 | 1 | |a Porcari, Aldostefano |e verfasserin |4 aut | |
| 700 | 1 | |a Rauf, Muhammad Umaid |e verfasserin |4 aut | |
| 700 | 1 | |a Starr, Neasa |e verfasserin |4 aut | |
| 700 | 1 | |a Ganesananthan, Sashiananthan |e verfasserin |4 aut | |
| 700 | 1 | |a Blakeney, Iona |e verfasserin |4 aut | |
| 700 | 1 | |a Kaza, Nandita |e verfasserin |4 aut | |
| 700 | 1 | |a Filisetti, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Bolhuis, Roos Eline |e verfasserin |4 aut | |
| 700 | 1 | |a Rowczenio, Dorota |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbertson, Janet |e verfasserin |4 aut | |
| 700 | 1 | |a Hutt, David |e verfasserin |4 aut | |
| 700 | 1 | |a Mahmood, Shameem |e verfasserin |4 aut | |
| 700 | 1 | |a Lachmann, Helen J |e verfasserin |4 aut | |
| 700 | 1 | |a Wechalekar, Ashutosh D |e verfasserin |4 aut | |
| 700 | 1 | |a Kotecha, Tushar |e verfasserin |4 aut | |
| 700 | 1 | |a Knight, Daniel S |e verfasserin |4 aut | |
| 700 | 1 | |a Coghlan, John G |e verfasserin |4 aut | |
| 700 | 1 | |a Petrie, Aviva |e verfasserin |4 aut | |
| 700 | 1 | |a Whelan, Carol J |e verfasserin |4 aut | |
| 700 | 1 | |a Venneri, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez-Naharro, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Hawkins, Phillip |e verfasserin |4 aut | |
| 700 | 1 | |a Fontana, Marianna |e verfasserin |4 aut | |
| 700 | 1 | |a Gillmore, Julian D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of heart failure |d 1999 |g 26(2024), 2 vom: 11. Feb., Seite 383-393 |w (DE-627)NLM106698575 |x 1879-0844 |7 nnns |
| 773 | 1 | 8 | |g volume:26 |g year:2024 |g number:2 |g day:11 |g month:02 |g pages:383-393 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ejhf.3088 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 26 |j 2024 |e 2 |b 11 |c 02 |h 383-393 | ||