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13 results on '"Job A.J. Verdonschot"'

1. Clustering of Cardiac Transcriptome Profiles Reveals Unique

Author

Job A.J. Verdonschot, Ping Wang, Kasper W.J. Derks, Michiel E. Adriaens, Sophie L.V.M. Stroeks, Michiel T.H.M. Henkens, Anne G. Raafs, Maurits Sikking, Bart de Koning, Arthur van den Wijngaard, Ingrid P.C. Krapels, Miranda Nabben, Han G. Brunner, and Stephane R.B. Heymans

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

2. Dyskalemia in people at increased risk for heart failure

Author

Luca Monzo, João Pedro Ferreira, John G.F. Cleland, Pierpaolo Pellicori, Beatrice Mariottoni, Job A.J. Verdonschot, Mark R. Hazebroek, Tim J. Collier, Joe J. Cuthbert, Burkert Pieske, Frank Edelmann, Johannes Petutschnigg, Javed Khan, Fozia Z. Ahmed, Nicolas Girerd, Erwan Bozec, Javier Díez, Arantxa González, Andrew L. Clark, Franco Cosmi, Jan A. Staessen, Stephane Heymans, Patrick Rossignol, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universidade do Porto = University of Porto, University of Glasgow, Department of Cardiology, Cortona Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], London School of Hygiene and Tropical Medicine (LSHTM), Castle Hill Hospital, University of Hull [United Kingdom], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Manchester University NHS Foundation Trust (MFT), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Department of Cardiovascular Sciences [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The Netherlands Heart Institute, European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Hyperkalaemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, heart failure prevention, hyperkalaemia, hypokalaemia, steroidal mineralocorticoid receptor antagonist, Heart failure prevention, Cardiology and Cardiovascular Medicine, Hypokalaemia, Steroidal mineralocorticoid receptor antagonist, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

AIMS: In people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia. METHODS AND RESULTS: The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at 5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration

Published
2022

3. Multicenter clinical and functional evidence reclassifies a recurrent noncanonical filamin C splice-altering variant

Author

Matthew J. O’Neill, Suet Nee Chen, Lynne Rumping, Renee Johnson, Marjon van Slegtenhorst, Andrew M. Glazer, Tao Yang, Joseph F. Solus, Julie Laudeman, Devyn W. Mitchell, Loren R. Vanags, Brett M. Kroncke, Katherine Anderson, Shanshan Gao, Job A.J. Verdonschot, Han Brunner, Debby Hellebrekers, Matthew R.G. Taylor, Dan M. Roden, Marja W. Wessels, Ronald H. Lekanne Dit Deprez, Diane Fatkin, Luisa Mestroni, and M. Benjamin Shoemaker

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Truncating variants in filamin C (FLNC) can cause arrhythmogenic cardiomyopathy (ACM) through haploinsufficiency. Noncanonical splice-altering variants may contribute to this phenotype. Objective: The purpose of this study was to investigate the clinical and functional consequences of a recurrent FLNC intronic variant of uncertain significance (VUS), c.970-4A>G. Methods: Clinical data in 9 variant heterozygotes from 4 kindreds were obtained from 5 tertiary health care centers. We used in silico predictors and functional studies with peripheral blood and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Isolated RNA was studied by reverse transcription polymerase chain reaction. iPSC-CMs were further characterized at baseline and after nonsense-mediated decay (NMD) inhibition, using quantitative polymerase chain reaction (qPCR), RNA-sequencing, and cellular electrophysiology. American College of Medical Genetics and Genomics (ACMG) criteria were used to adjudicate variant pathogenicity. Results: Variant heterozygotes displayed a spectrum of disease phenotypes, spanning from mild ventricular dysfunction with palpitations to severe ventricular arrhythmias requiring device shocks or progressive cardiomyopathy requiring heart transplantation. Consistent with in silico predictors, the c.970-4A>G FLNC variant activated a cryptic splice acceptor site, introducing a 3-bp insertion containing a premature termination codon. NMD inhibition upregulated aberrantly spliced transcripts by qPCR and RNA-sequencing. Patch clamp studies revealed irregular spontaneous action potentials, increased action potential duration, and increased sodium late current in proband-derived iPSC-CMs. These findings fulfilled multiple ACMG criteria for pathogenicity. Conclusion: Clinical, in silico, and functional evidence support the prediction that the intronic c.970-4A>G VUS disrupts splicing and drives ACM, enabling reclassification from VUS to pathogenic.

Published
2023

4. Left Atrial Function in Patients with Titin Cardiomyopathy

Author

Michiel T.H.M. Henkens, Anne G. Raafs, Tim van Loon, Jacqueline L. Vos, Arthur van den Wijngaard, Han G. Brunner, Ingrid P.C. Krapels, Christian Knackstedt, Suzanne Gerretsen, Mark R. Hazebroek, Kevin Vernooy, Robin Nijveldt, Joost Lumens, and Job A.J. Verdonschot

Subjects
Cardiology and Cardiovascular Medicine
Published
2023

5. Myocardial Fibrosis Assessment Using T1 and ECV Mapping With Histologic Validation in Chronic Dilated Cardiomyopathy

Author

Anne G. Raafs, Bouke P. Adriaans, Michiel T.H.M. Henkens, Job A.J. Verdonschot, Mitch J.F.G. Ramaekers, Suzanne Gommers, Myrurgia A. Abdul Hamid, Simon Schalla, Christian Knackstedt, Vanessa.P.M. van Empel, Hans-Peter Brunner-la Rocca, J.E. Wildberger, Sebastiaan C.A.M. Bekkers, Mark R. Hazebroek, Cardiologie, RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - B06 Imaging, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H01 Clinical atrial fibrillation, and MUMC+: MA Cardiologie (3)

Subjects
Cardiomyopathy, Dilated, Predictive Value of Tests, Myocardium, Contrast Media, Humans, Magnetic Resonance Imaging, Cine, Radiology, Nuclear Medicine and imaging, Cardiomyopathies, Cardiology and Cardiovascular Medicine, Fibrosis, EXTRACELLULAR VOLUME
Published
2022

6. Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data

Author

Upasana Tayal, Job A.J. Verdonschot, Mark R. Hazebroek, James Howard, John Gregson, Simon Newsome, Ankur Gulati, Chee Jian Pua, Brian P. Halliday, Amrit S. Lota, Rachel J. Buchan, Nicola Whiffin, Lina Kanapeckaite, Resham Baruah, Julian W.E. Jarman, Declan P. O’Regan, Paul J.R. Barton, James S. Ware, Dudley J. Pennell, Bouke P. Adriaans, Sebastiaan C.A.M. Bekkers, Jackie Donovan, Michael Frenneaux, Leslie T. Cooper, James L. Januzzi, John G.F. Cleland, Stuart A. Cook, Rahul C. Deo, Stephane R.B. Heymans, Sanjay K. Prasad, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - B06 Imaging, RS: Carim - H01 Clinical atrial fibrillation, MUMC+: MA Cardiologie (9), MUMC+: MA Med Staf Spec Cardiologie (9), FONDATION LEDUCQ, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Cardiomyopathy, Dilated, Male, Proteomics, Cardiac & Cardiovascular Systems, STRATEGIES, Cardiomyopathy, heart, 1117 Public Health and Health Services, proteomics, Humans, POSITION STATEMENT, 1102 Cardiorespiratory Medicine and Haematology, Science & Technology, Dilated/diagnosis, Stroke Volume, Middle Aged, R1, Fibrosis, machine learning, Cardiovascular System & Hematology, Creatinine, Cardiomyopathy, Dilated/diagnosis, Cardiovascular System & Cardiology, ESC WORKING GROUP, Female, Cardiology and Cardiovascular Medicine, Cardiomyopathies, Life Sciences & Biomedicine
Abstract

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine. ispartof: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY vol:79 issue:22 pages:2219-2232 ispartof: location:United States status: published

Published
2022

7. Improving diagnosis and risk stratification across the ejection fraction spectrum: the Maastricht Cardiomyopathy registry

Author

Michiel T.H.M. Henkens, Jerremy Weerts, Job A.J. Verdonschot, Anne G. Raafs, Sophia Stroeks, Maurits A. Sikking, Hesam Amin, Sanne G.J. Mourmans, Chrit B.G. Geraeds, Sandra Sanders‐van Wijk, Arantxa Barandiarán Aizpurua, Nicole H.M.K. Uszko‐Lencer, Ingrid P.C. Krapels, Petra F.G. Wolffs, Han G. Brunner, Rick E.W. Leeuwen, Wouter Verhesen, Simon M. Schalla, Antonius W.M. Stipdonk, Christian Knackstedt, Xiaofei Li, Myrurgia A. Abdul Hamid, Pieter Paassen, Mark R. Hazebroek, Kevin Vernooy, Hans‐Peter Brunner‐La Rocca, Vanessa P.M. Empel, Stephane R.B. Heymans, MUMC+: DA Pat Toegelatenen (9), MUMC+: DA Pat AIOS (9), Cardiologie, RS: Carim - H02 Cardiomyopathy, MUMC+: DA KG Lab Bedrijfsbureau (9), MUMC+: DA KG AIOS (9), MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), RS: Carim - H01 Clinical atrial fibrillation, MUMC+: MA Med Staf Artsass Cardiologie (9), MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: DA MMI Staf (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Med Microbiol, Infect Dis & Infect Prev, RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: Carim - B06 Imaging, RS: Carim - H06 Electro mechanics, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: DA Pat Pathologie (9), RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Interne Geneeskunde, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), and MUMC+: MA Cardiologie (3)

Subjects
Registry, Cardiac & Cardiovascular Systems, SOCIETY, ESC, Heart failure, GUIDELINES, Risk Assessment, Ventricular Function, Left, CLASSIFICATION, Diagnosis, MANAGEMENT, Humans, EPIDEMIOLOGY, Registries, Biological Specimen Banks, CARDIOLOGY, Science & Technology, Stroke Volume, Prognosis, Quality of Life, Cardiovascular System & Cardiology, HEART-FAILURE, Cardiology and Cardiovascular Medicine, Cardiomyopathies, Life Sciences & Biomedicine, TASK-FORCE
Abstract

AIMS: Heart failure (HF) represents a clinical syndrome resulting from different aetiologies and degrees of heart diseases. Among these, a key role is played by primary heart muscle disease (cardiomyopathies), which are the combination of multifactorial environmental insults in the presence or absence of a known genetic predisposition. The aim of the Maastricht Cardiomyopathy registry (mCMP-registry; NCT04976348) is to improve (early) diagnosis, risk stratification, and management of cardiomyopathy phenotypes beyond the limits of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: The mCMP-registry is an investigator-initiated prospective registry including patient characteristics, diagnostic measurements performed as part of routine clinical care, treatment information, sequential biobanking, quality of life and economic impact assessment, and regular follow-up. All subjects aged ≥16 years referred to the cardiology department of the Maastricht University Medical Center (MUMC+) for HF-like symptoms or cardiac screening for cardiomyopathies are eligible for inclusion, irrespective of phenotype or underlying causes. Informed consented subjects will be followed up for 15 years. Two central approaches will be used to answer the research questions related to the aims of this registry: (i) a data-driven approach to predict clinical outcome and response to therapy and to identify clusters of patients who share underlying pathophysiological processes; and (ii) a hypothesis-driven approach in which clinical parameters are tested for their (incremental) diagnostic, prognostic, or therapeutic value. The study allows other centres to easily join this initiative, which will further boost research within this field. CONCLUSIONS: The broad inclusion criteria, systematic routine clinical care data-collection, extensive study-related data-collection, sequential biobanking, and multi-disciplinary approach gives the mCMP-registry a unique opportunity to improve diagnosis, risk stratification, and management of HF and (early) cardiomyopathy phenotypes beyond the LVEF limits. ispartof: ESC HEART FAILURE vol:9 issue:2 pages:1463-1470 ispartof: location:England status: published

Published
2022

9. Natural History of MYH7-Related Dilated Cardiomyopathy

Author

Fernando de Frutos, Juan Pablo Ochoa, Marina Navarro-Peñalver, Annette Baas, Jesper Vandborg Bjerre, Esther Zorio, Irene Méndez, Rebeca Lorca, Job A.J. Verdonschot, Pablo Elpidio García-Granja, Zofia Bilinska, Diane Fatkin, M. Eugenia Fuentes-Cañamero, José M. García-Pinilla, María I. García-Álvarez, Francesca Girolami, Roberto Barriales-Villa, Carles Díez-López, Luis R. Lopes, Karim Wahbi, Ana García-Álvarez, Ibon Rodríguez-Sánchez, Javier Rekondo-Olaetxea, José F. Rodríguez-Palomares, María Gallego-Delgado, Benjamin Meder, Milos Kubanek, Frederikke G. Hansen, María Alejandra Restrepo-Córdoba, Julián Palomino-Doza, Luis Ruiz-Guerrero, Georgia Sarquella-Brugada, Alberto José Perez-Perez, Francisco José Bermúdez-Jiménez, Tomas Ripoll-Vera, Torsten Bloch Rasmussen, Mark Jansen, Maria Sabater-Molina, Perry M. Elliot, Pablo Garcia-Pavia, Eva Cabrera-Romero, Marta Cobo-Marcos, Luis Escobar-Lopez, Fernando Domínguez, Esther González-López, Juan Ramón Gimeno-Blanes, Dennis Dooijes, Bernabé López Ledesma, Inés Roche Fortea, Javier Bermejo, Maria Angeles Espinosa, Ana Isabel Fernández, Silvia Vilches, Cristina Gómez, Juan Gómez, Eliecer Coto, José Julián Rodríguez Reguero, S.R.B. Heymans, H.G. Brunner, Javier López-Díaz, Grażyna Truszkowska, Rafal Ploski, Przemysław Chmielewski, Renee Johnson, Ainhoa Robles-Mezcua, Arancha Díaz-Expósito, Alejandro I. Pérez-Cabeza, Clara Jiménez-Rubio, Vicente Climent Payá, Silvia Favilli, Petros Syrris, Douglas Cannie, Clarisse Billon, Angela Lopez-Sainz, Margarita Calvo, Ángela Cacicedo Fernández de Bobadilla, Jose Juan Onaindia-Gandarias, Larraitz Gaztañaga-Arantzamendi, Estibaliz Zamarreño-Golvano, Javier Limeres, Laura Gutiérrez-García, Eduardo Villacorta, Jan Haas, Alice Krebsova, Jens Mogensen, Sergi Cesar, Oscar Campuzano, Raúl Franco Gutiérrez, Jorge Alvarez-Rubio, David Cremer-Luengos, Guido Antoniutti, Fiama Caimi-Martinez, Rosa Macías, Juan Jiménez-Jáimez, María Luisa Peña-Peña, Salvador Lucas Díez-Aja López, Tania Pino Acereda, Blanca Arnáez Corada, Jesús Piqueras-Flores, Martin Negreira-Caamaño, Jorge Martinez-del Río, María Victoria Mogollón Jiménez, Elena Villanueva, José Luis Gonzáles, Adrián Fernández, Ulises Toscanini, Lilian E. Favaloro, Carlota Hernández Díez, MUMC+: DA KG Lab Bedrijfsbureau (9), MUMC+: DA KG AIOS (9), RS: Carim - H02 Cardiomyopathy, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Ciencia e Innovación (España), Fundación ProCNIC, Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, ERA-CVD framework, Dutch Heart Foundation, Victor Chang Cardiac Research Institute, NSW Health, Clinical Academic Research Partnerships (CARP), Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), Informatics for Life (Klaus Tschira Foundation), Ministry of Health, Czech Republic, and Institute for Clinical and Experimental Medicine–IKEM

Subjects
Adult, Cardiomyopathy, Dilated, Heart Failure, Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Myocardiopathies, Adolescent, Myosin Heavy Chains, Ventricular Remodeling, Miocardiopaties, Arrhythmias, Cardiac, Middle Aged, dilated cardiomyopathy, Young Adult, Phenotype, MYH7, Genetics, Humans, Female, genetics, Cardiology and Cardiovascular Medicine, Cardiac Myosins, Genètica
Abstract

Instituto de Salud Carlos III (ISCIII), European Regional Development Fund/European Social Fund "A way to make Europe"/" Investing in your future" [PI18/0004, PI20/0320, PT17/0015/0043]; ISCIII; MCIN; Pro-CNIC Foundation; Severo Ochoa Centers of Excellence program [CEX2020-001041-S]; ISCIII [CM20/00101], Frutos F. de, Ochoa JP, Navarro-Peñalver M, Baas A, Bjerre JV, Zorio E, Méndez I, Lorca R, Verdonschot JAJ, García-Granja PE, Bilinska Z, Fatkin D, Fuentes-Cañamero ME, García-Pinilla JM, García-Álvarez MI, Girolami F, Barriales-Villa R, Díez-López C, Lopes LR, Wahbi K, García-Álvarez A, Rodríguez-Sánchez I, Rekondo-Olaetxea J, Rodríguez-Palomares JF, Gallego-Delgado M, Meder B, Kubanek M, Hansen FG, Restrepo-Córdoba MA, Palomino-Doza J, Ruiz-Guerrero L, Sarquella-Brugada G, Perez-Perez AJ, Bermúdez-Jiménez FJ, Ripoll-Vera T, Rasmussen TB, Jansen M, Sabater-Molina M, Elliot PM, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators

Published
2022

10. Reply

Author

Anne G. Raafs, Michiel T.H.M. Henkens, Jacqueline L. Vos, Robin Nijveldt, and Job A.J. Verdonschot

Subjects
Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Published
2022

11. The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Author

Job A.J. Verdonschot, JoÃo Pedro Ferreira, Anne Pizard, Pierpaolo Pellicori, Hans-Peter Brunner La Rocca, Andrew L. Clark, Franco Cosmi, Joe Cuthbert, Nicolas Girerd, Olivia J. Waring, Michiel H.T.M. Henkens, Beatrice Mariottoni, Johannes Petutschnigg, Patrick Rossignol, Mark R. Hazebroek, John G.F. Cleland, Faiez Zannad, Stephane R.B. Heymans, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, University of Hull [United Kingdom], Cortona Hospital, Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement N° 305507 (HOMAGE). S.H.: This manuscript has been possible thanks to the support of the the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, MUMC+: MA Med Staf Artsass Cardiologie (9), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Department of Cardiology, Cortona Hospital

Subjects
Male, Proteomics, obesity, Cardiac & Cardiovascular Systems, heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, LEPTIN, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PEOPLE, Glucose Intolerance, Humans, Obesity, 030304 developmental biology, Mineralocorticoid Receptor Antagonists, 0303 health sciences, INSULIN-RESISTANCE, Science & Technology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, spironolactone, ADRENOMEDULLIN, FAT, Cardiovascular System & Cardiology, biomarker, Female, ADIPOKINE, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Biomarkers
Abstract

BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66). CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure. ispartof: JOURNAL OF CARDIAC FAILURE vol:28 issue:5 pages:778-786 ispartof: location:United States status: published

Published
2022

12. Influence of ejection fraction on biomarker expression and response to spironolactone in people at risk of heart failure: findings from the HOMAGE trial

Author

João Pedro Ferreira, Job A.J. Verdonschot, Nicolas Girerd, Erwan Bozec, Pierpaolo Pellicori, Timothy Collier, Beatrice Mariottoni, Franco Cosmi, Mark Hazebroek, Joe Cuthbert, Johannes Petutschnigg, Stephane Heymans, Jan A. Staessen, Burkert Pieske, Frank Edelman, Andrew L. Clark, Javier Díez, Arantxa González, Patrick Rossignol, John G. Cleland, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Glasgow, London School of Hygiene and Tropical Medicine (LSHTM), Cortona Hospital, University of Hull [United Kingdom], Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Health Carlos III, Universidad de Navarra [Pamplona] (UNAV), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), MUMC+: DA KG Lab Centraal Lab (9), RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Artsass Cardiologie (9), Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Heart Failure, Inflammation, Ejection fraction, INTERLEUKIN-8, IMPACT, PROGNOSTIC IMPORTANCE, Stroke Volume, Spironolactone, Fibrosis, Ventricular Function, Left, DISEASE, EVENTS, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, S100A12, Tissue Plasminogen Activator, Natriuretic Peptide, Brain, cardiovascular system, Humans, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Biomarkers, Mineralocorticoid Receptor Antagonists, circulatory and respiratory physiology
Abstract

Aims: \ud Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.\ud \ud Methods and results: \ud HOMAGE enrolled patients aged >60 years at high risk of developing HF with a LVEF ≥45%. Overall, 527 patients were randomized to either spironolactone or standard of care for ≈9 months, and 276 circulating proteins were measured using Olink® technology. A total of 364 patients had available LVEF determined by the Simpson's biplane method. The respective LVEF tertiles were: tertile 1: 65% (n = 121). Patients with a LVEF >65% had smaller left ventricular chamber size and volumes, and lower natriuretic peptide levels. Compared to patients with a LVEF 65% had higher levels of circulating c-c motif chemokine ligand-23 and interleukin-8, and lower levels of tissue plasminogen activator, brain natriuretic peptide (BNP), S100 calcium binding protein A12, and collagen type I alpha 1 chain (COL1A1). Spironolactone significantly reduced the circulating levels of BNP and COL1A1 without significant treatment-by-LVEF heterogeneity: BNP change β = −0.36 log2 and COL1A1 change β = −0.16 log2 (p 0.1 for both). Spironolactone increased LVEF from baseline to month 9 by 1.1% (p = 0.007).\ud \ud Conclusion: \ud Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.

Published
2022

13. Dynamic Ejection Fraction Trajectory in Patients With Dilated Cardiomyopathy With a Truncating Titin Variant

Author

Michiel T.H.M. Henkens, Sophie L.V.M. Stroeks, Anne G. Raafs, Maurits A. Sikking, Jasper Tromp, Wouter Ouwerkerk, Mark R. Hazebroek, Ingrid P.C. Krapels, Christian Knackstedt, Arthur van den Wijngaard, Han G. Brunner, Stephane R.B. Heymans, Job A.J. Verdonschot, Dermatology, Cardiologie, RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Artsass Cardiologie (9), MUMC+: DA KG Polikliniek (9), MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA Klinische Genetica (5), Klinische Genetica, and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
Cardiomyopathy, Dilated, Heart Failure, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Mutation, Humans, Connectin, Stroke Volume, Cardiology and Cardiovascular Medicine
Abstract

Contains fulltext : 284809.pdf (Publisher’s version ) (Open Access)

Published
2022

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