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Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial.
Ravassa, Susana; López, Begoña; Ferreira, João Pedro; Girerd, Nicolas; Bozec, Erwan; Pellicori, Pierpaolo; Mariottoni, Beatrice; Cosmi, Franco; Hazebroek, Mark; Verdonschot, Job A J; Cuthbert, Joe; Petutschnigg, Johannes; Moreno, María U; Heymans, Stephane; Staessen, Jan A; Pieske, Burkert; Edelmann, Frank; Clark, Andrew L; Cleland, John G F; Zannad, Faiez; Díez, Javier; González, Arantxa.
Afiliação
  • Ravassa S; Program of Cardiovascular Diseases, CIMA, Universidad de Navarra and IdiSNA, Pamplona, Spain.
  • López B; CIBERCV, Carlos III Institute of Health, Madrid, Spain.
  • Ferreira JP; Program of Cardiovascular Diseases, CIMA, Universidad de Navarra and IdiSNA, Pamplona, Spain.
  • Girerd N; CIBERCV, Carlos III Institute of Health, Madrid, Spain.
  • Bozec E; Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France.
  • Pellicori P; Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France.
  • Mariottoni B; Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France.
  • Cosmi F; Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
  • Hazebroek M; Department of Cardiology, Cortona Hospital, Arezzo, Italy.
  • Verdonschot JAJ; Department of Cardiology, Cortona Hospital, Arezzo, Italy.
  • Cuthbert J; Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Petutschnigg J; Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Moreno MU; Department of Cardiology, University of Hull, Castle Hill Hospital, Cottingham, UK.
  • Heymans S; Department of Internal Medicine and Cardiology Campus Virchow Klinikum, Charité University Medicine Berlin and German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
  • Staessen JA; Program of Cardiovascular Diseases, CIMA, Universidad de Navarra and IdiSNA, Pamplona, Spain.
  • Pieske B; CIBERCV, Carlos III Institute of Health, Madrid, Spain.
  • Edelmann F; Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Clark AL; Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen (APPREMED), Mechelen, Belgium.
  • Cleland JGF; Biomedical Sciences Group, Faculty of Medicine, University of Leuven, Leuven, Belgium.
  • Zannad F; Department of Internal Medicine and Cardiology Campus Virchow Klinikum, Charité University Medicine Berlin and German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
  • Díez J; Berlin Institute of Health, Berlin, Germany.
  • González A; Department of Internal Medicine and Cardiology Campus Virchow Klinikum, Charité University Medicine Berlin and German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
Eur J Heart Fail ; 24(2): 321-331, 2022 02.
Article em En | MEDLINE | ID: mdl-34841615
AIMS: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial. METHODS AND RESULTS: Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesspiro/control : -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m2 ; interaction pacross-tertiles  = 0.005; interaction pthird tertile  = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differencesspiro/control : -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction pacross-tertiles  = 0.09; interaction pthird tertile < 0.001]. CONCLUSIONS: These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Remodelamento Atrial / Insuficiência Cardíaca Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Eur J Heart Fail Assunto da revista: CARDIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Remodelamento Atrial / Insuficiência Cardíaca Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Eur J Heart Fail Assunto da revista: CARDIOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Espanha