Cardiomuscular biomarkers in the diagnosis and prognostication of immune checkpoint Inhibitor myocarditis
Lorenz H. Lehmann
(1)
,
Markus B. Heckmann
(1)
,
Guillaume Bailly
(2)
,
Daniel Finke
(1)
,
Adrien Procureur
(2)
,
John R. Power
(3)
,
Frederic Stein
(1)
,
Marie Bretagne
(2)
,
Stéphane Ederhy
(4)
,
Charlotte Fenioux
(2)
,
Omar Hamwy
(2)
,
Elisa Funck-Brentano
(5)
,
Emanuela Romano
(6)
,
Laurence Pieroni
(7)
,
Jan Münster
(1)
,
Yves Allenbach
(8, 2)
,
Céline Anquetil
(2)
,
Sarah Leonard-Louis
(2)
,
Nicolas L Palaskas
(9)
,
Salim S. Hayek
(10)
,
Hugo A. Katus
(1)
,
Evangelos Giannitsis
(1)
,
Norbert Frey
(1)
,
Ziya Kaya
(1)
,
Javid Moslehi
(11)
,
Edi Prifti
(12, 13)
,
Joe-Elie Salem
(2)
1
DZHK -
German Center for Cardiovascular Research
2 CHU Pitié-Salpêtrière [AP-HP]
3 UC San Diego - University of California [San Diego]
4 CHU Saint-Antoine [AP-HP]
5 Hôpital Ambroise Paré [AP-HP]
6 Institut Curie [Paris]
7 CHU Tenon [AP-HP]
8 Centre de recherche en Myologie – U974 SU-INSERM
9 MD Anderson Cancer Center [Houston]
10 University of Michigan [Ann Arbor]
11 UC San Francisco - University of California [San Francisco]
12 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
13 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
2 CHU Pitié-Salpêtrière [AP-HP]
3 UC San Diego - University of California [San Diego]
4 CHU Saint-Antoine [AP-HP]
5 Hôpital Ambroise Paré [AP-HP]
6 Institut Curie [Paris]
7 CHU Tenon [AP-HP]
8 Centre de recherche en Myologie – U974 SU-INSERM
9 MD Anderson Cancer Center [Houston]
10 University of Michigan [Ann Arbor]
11 UC San Francisco - University of California [San Francisco]
12 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
13 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
Markus B. Heckmann
- Fonction : Auteur
- PersonId : 1381828
- ORCID : 0000-0002-3085-1282
Daniel Finke
- Fonction : Auteur
- PersonId : 1230808
- ORCID : 0000-0002-0536-7536
Adrien Procureur
- Fonction : Auteur
- PersonId : 1341004
- ORCID : 0000-0003-3486-5208
John R. Power
- Fonction : Auteur
- PersonId : 1168201
- ORCID : 0000-0003-4254-4447
Stéphane Ederhy
- Fonction : Auteur
- PersonId : 772992
- ORCID : 0000-0002-0792-2521
- IdRef : 095495304
Elisa Funck-Brentano
- Fonction : Auteur
- PersonId : 1309825
- ORCID : 0000-0002-1092-0789
Jan Münster
- Fonction : Auteur
- PersonId : 1381830
- ORCID : 0009-0003-1687-4570
Yves Allenbach
- Fonction : Auteur
- PersonId : 977142
- IdHAL : yves-allenbach
- ORCID : 0000-0002-3185-7993
- IdRef : 160377293
Nicolas L Palaskas
- Fonction : Auteur
- PersonId : 813502
- ORCID : 0000-0001-7565-1797
Salim S. Hayek
- Fonction : Auteur
- PersonId : 1341005
- ORCID : 0000-0003-0180-349X
Evangelos Giannitsis
- Fonction : Auteur
- PersonId : 1381831
- ORCID : 0000-0002-1025-2872
Ziya Kaya
- Fonction : Auteur
- PersonId : 1381832
- ORCID : 0000-0002-3745-0836
Javid Moslehi
- Fonction : Auteur
- PersonId : 1230699
- ORCID : 0000-0001-5443-4312
Edi Prifti
- Fonction : Auteur
- PersonId : 1151183
- IdHAL : edi-prifti
- ORCID : 0000-0001-8861-1305
- IdRef : 155572822
Joe-Elie Salem
- Fonction : Auteur
- PersonId : 777251
- IdHAL : joe-elie-salem
- ORCID : 0000-0002-0331-3307
- IdRef : 160947227
Résumé
BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P =0.03 versus cTnT), and 43 of 57 ([75%] P <0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P <0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco–German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2–16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2–38.0]; P <0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients ( P <0.001), respectively. CONCLUSIONS: cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.
Domaines
ImmunothérapieFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Résumé |
en
BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P =0.03 versus cTnT), and 43 of 57 ([75%] P <0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P <0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco–German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2–16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2–38.0]; P <0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients ( P <0.001), respectively. CONCLUSIONS: cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.
|
Titre |
en
Cardiomuscular biomarkers in the diagnosis and prognostication of immune checkpoint Inhibitor myocarditis
|
Auteur(s) |
Lorenz H. Lehmann
1
, Markus B. Heckmann
1
, Guillaume Bailly
2
, Daniel Finke
1
, Adrien Procureur
2
, John R. Power
3
, Frederic Stein
1
, Marie Bretagne
2
, Stéphane Ederhy
4
, Charlotte Fenioux
2
, Omar Hamwy
2
, Elisa Funck-Brentano
5
, Emanuela Romano
6
, Laurence Pieroni
7
, Jan Münster
1
, Yves Allenbach
8, 2
, Céline Anquetil
2
, Sarah Leonard-Louis
2
, Nicolas L Palaskas
9
, Salim S. Hayek
10
, Hugo A. Katus
1
, Evangelos Giannitsis
1
, Norbert Frey
1
, Ziya Kaya
1
, Javid Moslehi
11
, Edi Prifti
12, 13
, Joe-Elie Salem
2
1
DZHK -
German Center for Cardiovascular Research
( 455355 )
- Allemagne
2
CHU Pitié-Salpêtrière [AP-HP]
( 353778 )
- 47-83 Boulevard de l'Hôpital, 75013 Paris
- France
3
UC San Diego -
University of California [San Diego]
( 300717 )
- UCSD, 9500 Gilman Dr., La Jolla, CA 92093 USA
- États-Unis
4
CHU Saint-Antoine [AP-HP]
( 454982 )
- 184, rue du Faubourg Saint-Antoine
75571 Paris cedex 12
- France
5
Hôpital Ambroise Paré [AP-HP]
( 300151 )
- 9, avenue Charles de Gaulle92104 Boulogne-Billancourt cedex
- France
6
Institut Curie [Paris]
( 301888 )
- 26 rue d'Ulm - 75248 Paris
- France
7
CHU Tenon [AP-HP]
( 328304 )
- 4 Rue de la Chine, 75020 Paris
- France
8
Centre de recherche en Myologie – U974 SU-INSERM
( 1053657 )
- Faculté de Médecine Sorbonne Université
Site Pitié Salpêtrière
105 boulevard de l’Hôpital
75013 Paris
- France
9
MD Anderson Cancer Center [Houston]
( 116559 )
- 1515 Holcombe Blvd, Houston, TX 77030
- États-Unis
10
University of Michigan [Ann Arbor]
( 24332 )
- 500 Church Street Ann Arbor, MI 48109-1090
- États-Unis
11
UC San Francisco -
University of California [San Francisco]
( 190541 )
- 505 Parnassus Ave, San Francisco, CA 94143
- États-Unis
12
UMMISCO -
Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
( 541946 )
- IRD France Nord - 32 avenue Henri Varagnat - 93143 Bondy cedex
- France
13
Nutriomics -
Nutrition et obésités: approches systémiques (UMR-S 1269)
( 1002956 )
- France
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Langue du document |
Anglais
|
Nom de la revue |
|
Volume |
148
|
Numéro |
6
|
Page/Identifiant |
473-486
|
Date de publication |
2023-06-15
|
Domaine(s) |
|
Mots-clés |
en
Myocarditis, Cardio-oncology, Pharmacology, Immune-checkpoint inhibitors, Adverse drug reactions, Biomarkers, Troponins
|
DOI | 10.1161/CIRCULATIONAHA.123.062405 |
Base Horizon | fdi:010090126 |
Fichier principal
Troponin paper vf - Clean.pdf ( 1.43 Mo
)
Télécharger
Troponin paper vf - Supp Data.pdf ( 2.22 Mo
)
Télécharger
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