@article{fdi:010090126,
  title = {{C}ardiomuscular biomarkers in the diagnosis and prognostication of immune checkpoint inhibitor myocarditis},
  author = {{L}ehmann, {L}. {H}. and {H}eckmann, {M}. {B}. and {B}ailly, {G}. and {F}inke, {D}. and {P}rocureur, {A}. and {P}ower, {J}. {R}. and {S}tein, {F}. and {B}retagne, {M}. and {E}derhy, {S}. and {F}enioux, {C}. and {H}amwy, {O}. and {F}unck-{B}rentano, {E}. and {R}omano, {E}. and {P}ieroni, {L}. and {M}unster, {J}. {P}. and {A}llenbach, {Y}. and {A}nquetil, {C}. and {L}eonard-{L}ouis, {S}. and {P}alaskas, {N}. {L}. and {H}ayek, {S}. {S}. and {K}atus, {H}. {A}. and {G}iannitsis, {E}. and {F}rey, {N}. and {K}aya, {Z}. and {M}oslehi, {J}. and {P}rifti, {E}di and {S}alem, {J}. {E}.},
  editor = {},
  language = {{ENG}},
  abstract = {{BACKGROUND}: {I}mmune checkpoint inhibitors ({ICI}s) are approved for multiple cancers but can result in {ICI}-associated myocarditis, an infrequent but life-threatening condition. {E}levations in cardiac biomarkers, specifically troponin-{I} (c{T}n{I}), troponin-{T} (c{T}n{T}), and creatine kinase ({CK}), are used for diagnosis. {H}owever, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. {METHODS}: {W}e analyzed the diagnostic accuracy and prognostic performances of c{T}n{I}, c{T}n{T}, and {CK} in patients with {ICI} myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units ({APHP} {S}orbonne, {P}aris, {F}rance and {H}eidelberg, {G}ermany). {A} total of 1751 (1 c{T}n{T} assay type), 920 (4 c{T}n{I} assay types), and 1191 {CK} sampling time points were available. {M}ajor 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. {D}iagnostic performance of c{T}n{I} and c{T}n{T} was also assessed in an international {ICI} myocarditis registry. {RESULTS}: {W}ithin 72 hours of admission, c{T}n{T}, c{T}n{I}, and {CK} were increased compared with upper reference limits ({URL}s) in 56 of 57 (98%), 37 of 42 ([88%] {P}=0.03 versus c{T}n{T}), and 43 of 57 ([75%] {P}<0.001 versus c{T}n{T}), respectively. {T}his increased rate of positivity for c{T}n{T} (93%) versus c{T}n{I} ([64%] {P}<0.001) on admission was confirmed in 87 independent cases from an international registry. {I}n the {F}ranco-{G}erman cohort, 24 of 60 (40%) patients developed ?1 {MACE} (total, 52; median time to first {MACE}, 5 [interquartile range, 2-16] days). {T}he highest value of c{T}n{T}:{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} c{T}n{T}:{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. c{T}n{T} was increased in all patients within 72 hours of the first {MACE} (23 of 23 [100%]), whereas c{T}n{I} 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}: c{T}n{T} is associated with {MACE} and is sensitive for diagnosis and surveillance in patients with {ICI} myocarditis. {A} c{T}n{T}:{URL} ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for {MACE}. {P}otential differences in diagnostic and prognostic performances between c{T}n{T} and c{T}n{I} as a function of the assays used deserve further evaluation in {ICI} myocarditis.},
  keywords = {biomarkers ; drug-related side effects and adverse reactions ; immune ; checkpoint inhibitors ; myocarditis ; pharmacology ; troponins ; {FRANCE} ; {ALLEMAGNE}},
  booktitle = {},
  journal = {{C}irculation},
  volume = {148},
  numero = {6},
  pages = {473--486},
  ISSN = {0009-7322},
  year = {2023},
  DOI = {10.1161/circulationaha.123.062405},
  URL = {https://www.documentation.ird.fr/hor/fdi:010090126},
}