Proteomic Profiling in Patients With Peripartum Cardiomyopathy: A Biomarker Study of the ESC EORP PPCM Registry.

Autor: Kodogo V; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa., Viljoen C; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa; Division of Cardiology, Department of Medicine, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, South Africa., Hoevelmann J; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa; Department of Internal Medicine III-Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Homburg, Germany., Chakafana G; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa; Department of Chemistry and Biochemistry, Hampton University, Hampton, Virginia, USA., Tromp J; Saw Swee Hock School of Public Health, National University of Singapore and the National University Health System, Singapore; Duke-National University of Singapore Medical School, Singapore., Farhan HA; University Hospital, Bagdad, Iraq., Goland S; Heart Institute, Kaplan Medical Center, Rehovot, affiliated with the Hebrew University, Jerusalem, Israel., van der Meer P; Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands., Karaye K; Department of Medicine, Bayero University, Kano, Nigeria., Kryczka K; Institute of Cardiology in Anin, Warsaw, Poland., Hilfiker-Kleiner D; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Jackson A; Institute of Cardiovascular and Medical Sciences, Glasgow University, Glasgow, United Kingdom., Mebazaa A; Paris Cité University, French National Institute of Health and Medical Research (INSERM) Cardiovascular MArkers in Stress Conditions (MASCOT), Paris, France; Department of Anesthesiology and Critical Care, Saint Louis Lariboisière Hospitals, Public Assistance Hospital of Paris, Paris, France., Böhm M; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa; Internal Medicine Clinic III -Cardiology, Angiology, and Internist Intensive Medicine, Saarland University Hospital, Saarland University, Homburg, Germany., Pieske B; Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany., Bauersachs J; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany., Bell L; Centre for Proteomic and Genomic Research, Cape Town, South Africa, Cape Town, South Africa., Sliwa K; Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, South Africa; Division of Cardiology, Department of Medicine, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, South Africa. Electronic address: karen.sliwa-hahnle@uct.ac.za.
Jazyk: angličtina
Zdroj: JACC. Heart failure [JACC Heart Fail] 2023 Dec; Vol. 11 (12), pp. 1708-1725. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.jchf.2023.07.028
Abstrakt: Background: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed.
Objectives: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision.
Methods: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation.
Results: Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs.
Conclusions: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.
Competing Interests: Funding Support and Author Disclosures Since the start of EORP, the following companies have supported the whole research program: Abbott Vascular International (2011-2021), Amgen Cardiovascular (2009-2018), AstraZeneca (2014-2021), Bayer AG (2009-2018), Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), Bristol-Myers Squibb and Pfizer Alliance (2011-2019), Daiichi Sankyo Europe GmbH (2011-2020), Daiichi Sankyo Europe GmbH and Eli Lilly and Company Alliance (2014-2017), Edwards Lifesciences (2016-2019), Gedeon Richter Plc (2014-2016), Menarini Int Op (2009-2012), Merck Sharp & Dohme–Merck and Co (2011-2014), Novartis Pharma AG (2014-2020), ResMed (2014-2016), Sanofi (2009-2011), Servier (2009-2021), and Vifor (2019-2022). Dr Hoevelmann has received speaker honoraria from Boehringer Ingelheim. Dr Tromp has received support from the National University of Singapore Start-up Grant, the Tier 1 Grant from the Ministry of Education, and the CS-IRG New Investigator Grant from the National Medical Research Council; has received consulting or speaker fees from Daiichi Sankyo, Boehringer Ingelheim, Roche Diagnostics, and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. Dr Sliwa has funded the proteomic analysis using her unconditional research grants; and has received support from Servier: Institut La Conference Hippocrate for funding of a statistical analysis program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE