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Observational Study
. 2025 Aug;18(8):e012816.
doi: 10.1161/CIRCHEARTFAILURE.125.012816. Epub 2025 May 15.

High-Sensitivity Cardiac Troponin I for Risk Stratification in Wild-Type Transthyretin Amyloid Cardiomyopathy

Laura De Michieli  1   2 , Giulio Sinigiani  1 , Gianluigi Guida  3 , Giulia Saturi  4 , Giuseppe Sena  4 , Teresa Maria Capovilla  5 , Anna Cantone  6 , Alessandro Cianca  7 , Alessandro Lupi  1 , Aldostefano Porcari  5 , Giacomo Tini  7 , Giuseppe Vergaro  8 , Francesco Cappelli  9 , Riccardo Albertini  10 , Matteo Bianco  11 , Roberta Mussinelli  12 , Matteo Serenelli  6 , Beatrice Musumeci  7 , Stefano Perlini  12 , Marco Merlo  5 , Simone Longhi  4 , Gianfranco Sinagra  5 , Martina Perazzolo Marra  1   2 , Sabino Iliceto  1   2 , Allan S Jaffe  13   14 , Giovanni Palladini  12   15 , Alberto Cipriani  1   2 , Paolo Milani  12   15
Affiliations
Observational Study

High-Sensitivity Cardiac Troponin I for Risk Stratification in Wild-Type Transthyretin Amyloid Cardiomyopathy

Laura De Michieli et al. Circ Heart Fail. 2025 Aug.

Abstract

Background: Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were: first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification.

Methods: Observational multicenter study of stable wild-type transthyretin amyloid cardiomyopathy patients from different cohorts using the Abbott Architect Stat hs-cTnI assay and the Beckman Coulter Access hs-cTnI assay (testing cohorts) and the Siemens Centaur XPT hs-cTnI assay (validation cohort). Outcome was all-cause mortality.

Results: In the Abbott cohort (n=136; median follow-up 22 [13-41] months; 31 [23%] deaths) and Beckman cohort (n=98; median follow-up 19 [12-28] months; 16 [16%] deaths), natural log-transformed hs-cTnI was an independent predictor of mortality (age- and sex-adjusted hazard ratio, 1.62 [95% CI, 1.11-2.35]; P=0.012 and 2.47 [95% CI, 1.48-4.14]; P<0.001, respectively). The best hs-cTnI threshold for 18-month mortality of the combined Abbott/Beckman cohorts (n=234) was 81 ng/L, rounded to 80 ng/L for simplicity of clinical use. A 2-variable staging system (based on the Mayo Clinic system) using hs-cTnI (>80 ng/L) and NPs (natriuretic peptides; NT-proBNP [N-terminal pro-B-type natriuretic peptide] >3000 ng/L or BNP [B-type natriuretic peptide] >250 ng/L) identified 3 groups with progressively worse prognosis. The staging system (using hs-cTnI >80 ng/L and NT-proBNP>3000 ng/L) was then applied to an independent cohort evaluated with the hs-cTnI Siemens assay (n=345, median follow-up 32 [24-42] months, 119 [34%] deaths). The significant differences between the groups were maintained.

Conclusions: In patients with wild-type transthyretin amyloid cardiomyopathy, hs-cTnI is a strong and independent predictor of mortality. A threshold of hs-cTnI of 80 ng/L for these 3 assays provides effective risk stratification alone and in a staging system with NP.

Keywords: amyloidosis; cardiomyopathies; prognosis; risk; troponin I.

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Conflict of interest statement

Dr De Michieli has received honoraria from Pfizer Inc, Alnylam Pharmaceuticals, AstraZeneca Spa, Takeda Pharmaceutical, and Sanofi. Dr Cipriani received honoraria from Pfizer Inc, Alnylam Pharmaceuticals, and AstraZeneca Spa. Dr Jaffe has consulted or presently consults for most of the major diagnostics companies, including Beckman Coulter, Abbott, Siemens, Ortho Diagnostics, ET Healthcare, Roche, Radiometer, Sphingotec, Amgen, and Novartis. He has stock in RCE Technologies. Dr Milani received honoraria from Janssen, Pfizer, and Prothena and is on the advisory boards of Janssen and Siemens Dr Cappelli received honoraria from Pfizer, Alnylam, Astra Zeneca, Novo Nordisk, Daiichi Sankyo, Amicus, and Bridgebio. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Prognostic performance of hs-cTnI (high-sensitivity cardiac troponin I) in the combined Abbott/Beckman cohort. A, Receiver-operating characteristic (ROC) curve of hs-cTnI for 18-month mortality in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). B, Kaplan-Meier curves for survival in patients with ATTRwt-CM and hs-cTnI values at baseline below/equal to (blue) or above (red) 80 ng/L. AUC indicates area under the curve; and HR, hazard ratio.
Figure 2.
Figure 2.
Kaplan-Meier (KM) curves for survival according to the 2-variable staging system based on hs-cTnI (high-sensitivity cardiac troponin I) >80 ng/L (Abbott/Beckman) and elevated natriuretic peptides (NPs). Elevated NPs are defined as NT-proBNP (N-terminal pro-B-type natriuretic peptide) >3000 ng/L or, if NT-proBNP not available, as BNP (B-type natriuretic peptide) >250 ng/L. Stage I is defined as both variables being below the cutoffs, stage II as 1 variable being above, and stage III as both variables being above. HR indicates hazard ratio.
Figure 3.
Figure 3.
Time-dependent area under the curve (AUC) of the different prognostic parameters in the Abbott/Beckman cohort. Below the table, the different AUC values at several time points are reported. The actual P values for global AUC comparisons between the different prognostic criteria can be found in Table S3. eGFR indicates estimated glomerular filtration rate; hs-cTnI, high-sensitivity cardiac troponin I; and NPs, natriuretic peptides. *Global value, not time-dependent AUC.
Figure 4.
Figure 4.
Kaplan-Meier (KM) curves for survival according to the 2-variable staging system based on hs-cTnI (high-sensitivity cardiac troponin I) >80 ng/L (Siemens) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) >3000 ng/L. Stage I is defined as both variables being below the cutoffs, stage II as 1 variable being above, and stage III as both variables being above. HR indicates hazard ratio.
Figure 5.
Figure 5.
hs-cTnI (high-sensitivity cardiac troponin I) for risk stratification in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM): summary findings. In patients with ATTRwt-CM evaluated at diagnosis with hs-cTnI with 1 of the 3 assays included in this study, a threshold of 80 ng/L can be used for risk stratification alone and combined in a staging system with natriuretic peptides, particularly NT-proBNP (N-terminal pro-B-type natriuretic peptide) >3000 ng/L (or BNP [B-type natriuretic peptide] >250 ng/L). KM indicates Kaplan-Meier.
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References

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