PMID- 35796209 OWN - NLM STAT- MEDLINE DCOM- 20221128 LR - 20230106 IS - 1879-0844 (Electronic) IS - 1388-9842 (Print) IS - 1388-9842 (Linking) VI - 24 IP - 10 DP - 2022 Oct TI - Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR-Preserved trial. PG - 1869-1878 LID - 10.1002/ejhf.2607 [doi] AB - AIMS: Biomarker-driven prognostic models incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved. METHODS AND RESULTS: Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, (iii) cardiovascular death, and (iv) HF hospitalization. PARAGON-HF was used as a validation cohort. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, New York Heart Association (NYHA) class III or IV, history of chronic obstructive pulmonary disease (COPD), insulin-treated diabetes, low haemoglobin, and a longer time since HF diagnosis were key predictors (eight variables, all p < 0.001). The consequent primary outcome risk score discriminated well (c-statistic = 0.75) with patients in the top 10th of risk having an event rate >22x higher than those in the bottom 10th. A model for HF hospitalization alone had even better discrimination (c = 0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for HF in patients across all risk levels. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality followed by history of COPD, low albumin, older age, left ventricular ejection fraction >/=50%, NYHA class III or IV and insulin-treated diabetes (eight variables, all p < 0.001). The mortality risk model had similar discrimination for all-cause and cardiovascular mortality (c-statistic = 0.72 for both). External validation provided c-statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all-cause death, and cardiovascular death, respectively. CONCLUSIONS: The combination of NT-proBNP and hs-cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive tool-kit facilitates the ready implementation of these risk models in routine clinical practice. CI - (c) 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. FAU - Pocock, Stuart J AU - Pocock SJ AD - Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. FAU - Ferreira, Joao Pedro AU - Ferreira JP AUID- ORCID: 0000-0002-2304-6138 AD - UnIC@Rise, Department of Surgery and Physiology, Faculty of Medicine, Cardiovascular Research and Development Center, University of Porto, Porto, Portugal. AD - Inserm, Centre d'Investigations Cliniques Plurithematique 1433, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Universite de Lorraine, Nancy, France. FAU - Packer, Milton AU - Packer M AD - Baylor Heart and Vascular Hospital, Baylor University Medical Center, Dallas, TX, USA. AD - Imperial College, London, UK. FAU - Zannad, Faiez AU - Zannad F AD - Inserm, Centre d'Investigations Cliniques Plurithematique 1433, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Universite de Lorraine, Nancy, France. FAU - Filippatos, Gerasimos AU - Filippatos G AD - National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Attikon University Hospital, Athens, Greece. FAU - Kondo, Toru AU - Kondo T AD - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. AD - British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - McMurray, John J V AU - McMurray JJV AD - British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Solomon, Scott D AU - Solomon SD AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Januzzi, James L AU - Januzzi JL AD - Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Iwata, Tomoko AU - Iwata T AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Salsali, Afshin AU - Salsali A AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, TX, USA. AD - Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Anker, Stefan D AU - Anker SD AD - Department of Cardiology, and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charite Universitatsmedizin, Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220724 PL - England TA - Eur J Heart Fail JT - European journal of heart failure JID - 100887595 RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 0 (Peptide Fragments) RN - 0 (Biomarkers) RN - 0 (Insulins) SB - IM CIN - Eur J Heart Fail. 2022 Oct;24(10):1879-1882. PMID: 36101506 MH - Humans MH - *Heart Failure MH - Stroke Volume MH - Prognosis MH - Ventricular Function, Left MH - Natriuretic Peptide, Brain/therapeutic use MH - Peptide Fragments/therapeutic use MH - Biomarkers MH - Chronic Disease MH - *Pulmonary Disease, Chronic Obstructive MH - *Insulins/therapeutic use PMC - PMC9796853 OTO - NOTNLM OT - Biomarkers OT - Heart failure with preserved ejection fraction OT - Risk model EDAT- 2022/07/08 06:00 MHDA- 2022/11/29 06:00 PMCR- 2022/12/28 CRDT- 2022/07/07 05:03 PHST- 2022/07/01 00:00 [revised] PHST- 2022/03/04 00:00 [received] PHST- 2022/07/02 00:00 [accepted] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/11/29 06:00 [medline] PHST- 2022/07/07 05:03 [entrez] PHST- 2022/12/28 00:00 [pmc-release] AID - EJHF2607 [pii] AID - 10.1002/ejhf.2607 [doi] PST - ppublish SO - Eur J Heart Fail. 2022 Oct;24(10):1869-1878. doi: 10.1002/ejhf.2607. Epub 2022 Jul 24.