Nasrien E Ibrahim1, Marc Afilalo2, Annabel Chen-Tournoux3, Robert H Christenson4, Hanna K Gaggin1, Judd E Hollander5, Peter Kastner6, Phillip D Levy7, Anika Mang6, Serge Masson8, John T Nagurney9, Richard M Nowak10, Peter S Pang11, W Frank Peacock12, Vinzent Rolny Dipl-Stat6, E Lea Walters13, James L Januzzi14. 1. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 2. Department of Emergency Medicine, McGill University and Emergency Department, Jewish General Hospital, Montreal, Quebec, Canada. 3. Cardiology Division, McGill University, Jewish General Hospital, Montreal, Canada. 4. Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland. 5. Department of Emergency Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. 6. Roche Diagnostics, Penzberg, Germany. 7. Department of Emergency Medicine, Wayne State University, Detroit, Michigan. 8. Roche Diagnostics, Rotkreuz, Switzerland. 9. Harvard Medical School, Boston, Massachusetts; Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts. 10. Department of Emergency Medicine, Wayne State University, Detroit, Michigan; Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan. 11. Department of Emergency Medicine and Cardiology Division, Indiana University School of Medicine, Indianapolis, Indiana. 12. Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas. 13. Department of Emergency Medicine, Loma Linda University School of Medicine, Loma Linda, California. 14. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org.
Abstract
OBJECTIVES: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. BACKGROUND: IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. METHODS: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. RESULTS: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). CONCLUSIONS: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.
OBJECTIVES: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. BACKGROUND:IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. METHODS: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. RESULTS: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). CONCLUSIONS: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.
Authors: Elena Palà; Alejandro Bustamante; Jorge Pagola; Jesus Juega; Jaume Francisco-Pascual; Anna Penalba; Maite Rodriguez; Mercedes De Lera Alfonso; Juan F Arenillas; Juan Antonio Cabezas; Soledad Pérez-Sánchez; Francisco Moniche; Reyes de Torres; Teresa González-Alujas; Josep Lluís Clúa-Espuny; Juan Ballesta-Ors; Domingo Ribas; Juan Acosta; Alonso Pedrote; Felipe Gonzalez-Loyola; Delicia Gentile Lorente; Miguel Ángel Muñoz; Carlos A Molina; Joan Montaner Journal: Front Cardiovasc Med Date: 2022-07-04
Authors: Anna Lisowska; Anna Szyszkowska; Małgorzata Knapp; Magda Łapińska; Marcin Kondraciuk; Inga Kamińska; Tomasz Hryszko; Katarzyna Ptaszyńska-Kopczyńska; Karol Kamiński Journal: Biomolecules Date: 2022-02-08