Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction

Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non‐invasively using 99mTc 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scintigraphy‐based diagnostic criteria. Our...

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Main Authors: L. Healy, G. Giblin, A. Gray, N. Starr, L. Murphy, D. O'Sullivan, E. Kavanagh, C. Howley, C. Tracey, E. Morrin, A. McDaid, A. Clarke, J.O. O'Neill, E. Joyce, M. O'Connell, N. G. Mahon
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Language:English
Published: Wiley 2025-04-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.15112
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author L. Healy
G. Giblin
A. Gray
N. Starr
L. Murphy
D. O'Sullivan
E. Kavanagh
C. Howley
C. Tracey
E. Morrin
A. McDaid
A. Clarke
J.O. O'Neill
E. Joyce
M. O'Connell
N. G. Mahon
author_facet L. Healy
G. Giblin
A. Gray
N. Starr
L. Murphy
D. O'Sullivan
E. Kavanagh
C. Howley
C. Tracey
E. Morrin
A. McDaid
A. Clarke
J.O. O'Neill
E. Joyce
M. O'Connell
N. G. Mahon
author_sort L. Healy
collection DOAJ
description Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non‐invasively using 99mTc 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scintigraphy‐based diagnostic criteria. Our aim was to determine the prevalence of ATTR‐CM in an undifferentiated HFpEF cohort with a DPD scintigraphy‐based screening protocol. Methods Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60 years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant. Results Eighty‐six subjects were prospectively enrolled: 56% female, mean age 77 ± 8 years, 63% New York Heart Association (NYHA) Class III and median N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) 1766 ng/L [inter‐quartile range (IQR) 731–3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild‐type ATTR‐CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy‐negative cohort, DPD scintigraphy‐positive patients were older (86 ± 3 vs. 76 ± 8 years), more frequently male (16% vs. 2%, P = 0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12 mm; P = 0.002) and higher high‐sensitivity troponin levels at diagnosis [78 ng/L (IQR 21–116) vs. 11 ng/L (IQR 9–17); P < 0.001]. Conclusions In an undifferentiated HFpEF cohort, 8% were found to have wild‐type ATTR‐CM using a DPD scintigraphy‐based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high‐sensitivity troponin levels.
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spelling doaj-art-15f8d55b97f342b8ac8eecc781ebd51f2025-08-20T03:01:47ZengWileyESC Heart Failure2055-58222025-04-011221176118210.1002/ehf2.15112Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fractionL. Healy0G. Giblin1A. Gray2N. Starr3L. Murphy4D. O'Sullivan5E. Kavanagh6C. Howley7C. Tracey8E. Morrin9A. McDaid10A. Clarke11J.O. O'Neill12E. Joyce13M. O'Connell14N. G. Mahon15Mater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandMater Misericordiae University Hospital Dublin IrelandAbstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasinglyrecognized cause of heart failure with preserved ejection fraction (HFpEF), which may be diagnosed non‐invasively using 99mTc 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scintigraphy‐based diagnostic criteria. Our aim was to determine the prevalence of ATTR‐CM in an undifferentiated HFpEF cohort with a DPD scintigraphy‐based screening protocol. Methods Patients with HFpEF [ejection fraction (EF) ≥50%] aged ≥60 years and no prior evaluation for cardiac amyloidosis or known monoclonal gammopathy attending a regional cardiology network were screened with DPD scintigraphy. Patients with positive myocardial uptake (Perugini grade 2 or 3) were tested for a monoclonal protein and transthyretin gene variant. Results Eighty‐six subjects were prospectively enrolled: 56% female, mean age 77 ± 8 years, 63% New York Heart Association (NYHA) Class III and median N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) 1766 ng/L [inter‐quartile range (IQR) 731–3703]. DPD scintigraphy was positive in seven patients (8%). Monoclonal gammopathy of undetermined significance was present in one out of seven patients, and no pathogenic TTR gene variant was identified. The prevalence of wild‐type ATTR‐CM was 8% of this cohort. Compared with the HFpEF DPD scintigraphy‐negative cohort, DPD scintigraphy‐positive patients were older (86 ± 3 vs. 76 ± 8 years), more frequently male (16% vs. 2%, P = 0.02), and had significantly greater left ventricular (LV) wall thickness (16 vs. 12 mm; P = 0.002) and higher high‐sensitivity troponin levels at diagnosis [78 ng/L (IQR 21–116) vs. 11 ng/L (IQR 9–17); P < 0.001]. Conclusions In an undifferentiated HFpEF cohort, 8% were found to have wild‐type ATTR‐CM using a DPD scintigraphy‐based screening protocol. Screening undifferentiated HFpEF patients is associated with a significant diagnostic yield, which can be further increased by targeting older males with increased LV wall thickness and elevated high‐sensitivity troponin levels.https://doi.org/10.1002/ehf2.15112amyloidosisDPD scintigraphyheart failureHFpEFtransthyretin
spellingShingle L. Healy
G. Giblin
A. Gray
N. Starr
L. Murphy
D. O'Sullivan
E. Kavanagh
C. Howley
C. Tracey
E. Morrin
A. McDaid
A. Clarke
J.O. O'Neill
E. Joyce
M. O'Connell
N. G. Mahon
Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
ESC Heart Failure
amyloidosis
DPD scintigraphy
heart failure
HFpEF
transthyretin
title Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
title_full Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
title_fullStr Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
title_full_unstemmed Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
title_short Prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
title_sort prevalence of transthyretin cardiac amyloidosis in undifferentiated heart failure with preserved ejection fraction
topic amyloidosis
DPD scintigraphy
heart failure
HFpEF
transthyretin
url https://doi.org/10.1002/ehf2.15112
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