Impact of Clonal Hematopoiesis in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.


Journal

Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365

Informations de publication

Date de publication:
18 10 2022
Historique:
received: 11 04 2022
revised: 13 07 2022
accepted: 03 08 2022
entrez: 13 10 2022
pubmed: 14 10 2022
medline: 18 10 2022
Statut: ppublish

Résumé

Clonal hematopoiesis of indeterminate potential (CHIP) is common in elderly individuals and is associated with an increased risk of both hematologic malignancies and cardiovascular disease. The impact of CHIP on the outcomes for patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) remains undetermined. The purpose of this study was to determine the prognostic impact of CHIP in CS after AMI. Blood samples were obtained at randomization from 446 patients included in the CULPRIT-SHOCK (Culprit Lesion Only vs Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock; NCT01927549) trial. CHIP was assessed using a next-generation sequencing approach targeting the most commonly mutated genes; the primary outcome at 30 days comprised all-cause mortality and renal replacement therapy. CHIP variants at ≥2% variant allele frequency were detected in 29% (n = 129), most commonly in the DNMT3A or TET2 genes, which harbored 47% and 36% of all mutations, respectively. Compared to non-CHIP patients, CHIP carriers were older and had decreased renal function and increased levels of N-terminal pro-B-type natriuretic peptide and inflammatory biomarkers. CHIP carriers had worse short-term outcomes measured either as mortality or as the combined clinical endpoint of mortality or severe renal failure within 30 days. Association of CHIP with the combined endpoint was independent of age and biomarkers reflecting kidney function, heart failure severity, and inflammation (OR: 1.83; 95% CI: 1.05-3.21; P = 0.03) but not significant regarding all-cause mortality (OR: 1.67; 95% CI: 0.96-2.90; P = 0.069). CHIP is frequent among AMI and CS patients and is associated with impaired clinical outcome. CHIP assessment may facilitate risk stratification in patients with CS and imply novel treatment targets. (Culprit Lesion Only vs Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

Sections du résumé

BACKGROUND
Clonal hematopoiesis of indeterminate potential (CHIP) is common in elderly individuals and is associated with an increased risk of both hematologic malignancies and cardiovascular disease. The impact of CHIP on the outcomes for patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) remains undetermined.
OBJECTIVES
The purpose of this study was to determine the prognostic impact of CHIP in CS after AMI.
METHODS
Blood samples were obtained at randomization from 446 patients included in the CULPRIT-SHOCK (Culprit Lesion Only vs Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock; NCT01927549) trial. CHIP was assessed using a next-generation sequencing approach targeting the most commonly mutated genes; the primary outcome at 30 days comprised all-cause mortality and renal replacement therapy.
RESULTS
CHIP variants at ≥2% variant allele frequency were detected in 29% (n = 129), most commonly in the DNMT3A or TET2 genes, which harbored 47% and 36% of all mutations, respectively. Compared to non-CHIP patients, CHIP carriers were older and had decreased renal function and increased levels of N-terminal pro-B-type natriuretic peptide and inflammatory biomarkers. CHIP carriers had worse short-term outcomes measured either as mortality or as the combined clinical endpoint of mortality or severe renal failure within 30 days. Association of CHIP with the combined endpoint was independent of age and biomarkers reflecting kidney function, heart failure severity, and inflammation (OR: 1.83; 95% CI: 1.05-3.21; P = 0.03) but not significant regarding all-cause mortality (OR: 1.67; 95% CI: 0.96-2.90; P = 0.069).
CONCLUSIONS
CHIP is frequent among AMI and CS patients and is associated with impaired clinical outcome. CHIP assessment may facilitate risk stratification in patients with CS and imply novel treatment targets. (Culprit Lesion Only vs Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

Identifiants

pubmed: 36229091
pii: S0735-1097(22)06564-0
doi: 10.1016/j.jacc.2022.08.740
pii:
doi:

Substances chimiques

Natriuretic Peptide, Brain 114471-18-0

Banques de données

ClinicalTrials.gov
['NCT01927549']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1545-1556

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures This work was supported by Helios Research Funding at the University of Leipzig and the German Federal Ministry of Education and Research within the framework of the e:Med research and funding concept (project SYMPATH, grant number 01ZX1906B). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Matthias Böhme (M)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

Steffen Desch (S)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany.

Maciej Rosolowski (M)

Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

Markus Scholz (M)

Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

Knut Krohn (K)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

Petra Büttner (P)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany.

Michael Cross (M)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

Janine Kirchberg (J)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

Karl-Philipp Rommel (KP)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany.

Janine Pöss (J)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany.

Anne Freund (A)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany.

Ronny Baber (R)

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Hospital, Leipzig, Germany.

Berend Isermann (B)

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Hospital, Leipzig, Germany.

Uta Ceglarek (U)

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Hospital, Leipzig, Germany.

Klaus H Metzeler (KH)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

Uwe Platzbecker (U)

Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany. Electronic address: uwe.platzbecker@medizin.uni-leipzig.de.

Holger Thiele (H)

Heart Center Leipzig at University of Leipzig, Department of Internal Medicine/Cardiology and Leipzig Heart Institute, Leipzig, Germany. Electronic address: holger.thiele@medizin.uni-leipzig.de.

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