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. 2024 Sep 12;3(10):101261.
doi: 10.1016/j.jacadv.2024.101261. eCollection 2024 Oct.

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

René Rettl  1 , Raffaella Calabretta  2 , Franz Duca  1 , Christina Kronberger  1 , Christina Binder  1 , Robin Willixhofer  1 , Michael Poledniczek  1 , Felix Hofer  1 , Carolina Doná  1 , Dietrich Beitzke  3 , Christian Loewe  3 , Christian Nitsche  1 , Christian Hengstenberg  1 , Roza Badr Eslam  1 , Johannes Kastner  1 , Jutta Bergler-Klein  1 , Marcus Hacker  2 , Andreas A Kammerlander  1
Affiliations

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

René Rettl et al. JACC Adv. .

Abstract

Background: The pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium.

Objectives: This study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM.

Methods: Forty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups.

Results: ATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, β = 0.139, P < 0.001), native T1 time (r = 0.432, β = 0.020, P = 0.005), RV-LS (r = 0.445, β = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, β = 2.842, P = 0.003), troponin T (r = 0.422, β = 0.048, P = 0.007), 6MWD (r = 0.385, β = -0.007, P = 0.017), and NAC stage (r = 0.490, β = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021).

Conclusions: In ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

Keywords: ATTR amyloidosis; ATTRwt-CM; CMR; ECV; SPECT/CT.

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Conflict of interest statement

Dr Rettl has received speaker fees and congress support from Akcea Therapeutics, Alnylam Pharmaceuticals, and Pfizer Inc, as well as research grants from 10.13039/100004319Pfizer Inc. Dr Duca has received speaker fees and congress support from 10.13039/501100015086AOP Orphan Pharmaceuticals GmbH, 10.13039/100006400Alnylam Pharmaceuticals, 10.13039/100004326Bayer AG, 10.13039/100004336Novartis AG, 10.13039/100004319Pfizer Inc and, as well as research grants from the 10.13039/501100015797Austrian Society of Cardiology and 10.13039/100004319Pfizer Inc. Dr Beitzke has received speaker fees from GE Healthcare and Siemens. Dr Nitsche receives speaker fees and research grants from 10.13039/100004319Pfizer Inc. Dr Badr Eslam has received speaker fees from Merck Sharp & Dohme Ges.m.b.H., AOP Orphan Pharmaceuticals GmbH, and OrphaCare GmbH, as well as research grants from OrphaCare GmbH and Astra Zeneca GmbH. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Patient Flowchart A total of 71 treatment-naïve ATTR-CM patients who underwent DPD SPECT/CT and CMR imaging were screened for the study. Reasons for study exclusion are depicted. ATTR-CM = transthyretin amyloid cardiomyopathy; ATTRwt-CM = wild-type ATTR-CM; CMR = cardiac magnetic resonance; DPD = 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; SPECT/CT = single-photon emission computed tomography/computed tomography; TTR = transthyretin.
Figure 2
Figure 2
Correlation: DPD Quantification and CMR Imaging Characteristics (A) Correlation between SUV retention index and extracellular volume. (B) Correlation between SUV retention index and native T1 time. (C) Correlation between SUV retention index and right ventricular longitudinal strain. CMR = cardiac magnetic resonance; DPD = 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; SUV = standardized uptake value.
Figure 3
Figure 3
Correlation: DPD Quantification and Clinical and Laboratory Characteristics (A) Correlation between SUV retention index and NT-proBNP. (B) Correlation between SUV retention index and troponin T. (C) Correlation between SUV retention index and 6-minute walk distance. DPD = 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; SUV = standardized uptake value.
Central Illustration
Central Illustration
Correlation of DPD Quantification With Myocardial Amyloid Burden, Longitudinal Cardiac Function, Cardiac Biomarkers, Exercise Capacity, and Disease Stage in ATTRwt-CM 6MWD = 6-minute walk distance; ATTRwt-CM = wild-type transthyretin amyloid cardiomyopathy; DPD = 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; ECV = extracellular volume; NAC = National Amyloidosis Centre; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; RV-LS = right ventricular longitudinal strain; SPECT/CT = single-photon emission computed tomography/computed tomography; SUV = standardized uptake value.
See this image and copyright information in PMC

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