PMID- 34423361 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20211124 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 42 IP - 43 DP - 2021 Nov 14 TI - Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial. PG - 4455-4464 LID - 10.1093/eurheartj/ehab579 [doi] AB - AIMS: The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (HFrEF). A risk model incorporating biomarkers and clinical variables has not been validated in contemporary heart failure (HF) trials. METHODS AND RESULTS: In EMPEROR-Reduced, 33 candidate variables were pre-selected. Multivariable Cox regression models were developed using stepwise selection for: (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, and (iii) cardiovascular mortality. A total of 3730 patients were followed up for a median of 16 months, 823 (22%) patients had a primary outcome and 515 (14%) patients died, of whom 389 (10%) died from a cardiovascular cause. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last HF hospitalization, longer time since HF diagnosis, lower systolic blood pressure, New York Heart Association (NYHA) Class III or IV, higher heart rate and peripheral oedema were key predictors (eight variables in total, all P < 0.001). The primary outcome risk score discriminated well (c-statistic = 0.73), with patients in the top 10th of risk having an event rate >9 times higher than those in the bottom 10th. Empagliflozin benefitted patients across risk levels for the primary outcome. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality, followed by NYHA Class III or IV and ischaemic aetiology (four variables in total, all P < 0.001). The mortality risk model presented good event discrimination for all-cause and cardiovascular mortality (c-statistic = 0.69 for both). These simple models were externally validated in the BIOSTAT-CHF study, achieving similar c-statistics. CONCLUSIONS: The combination of NT-proBNP and hs-cTnT with a small number of readily available clinical variables provides prognostic assessment for patients with HFrEF. This predictive tool kit can be easily implemented for routine clinical use. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Pocock, Stuart J AU - Pocock SJ AUID- ORCID: 0000-0003-2212-4007 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 - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques Plurithematique 1433, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. AD - Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. FAU - Gregson, John AU - Gregson J AUID- ORCID: 0000-0001-6084-166X AD - Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. FAU - Anker, Stefan D AU - Anker SD AD - Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Butler, Javed AU - Butler J AD - Department of Medicine, University of Mississippi, Jackson. FAU - Filippatos, Gerasimos AU - Filippatos G AUID- ORCID: 0000-0002-5640-0332 AD - Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. FAU - Gollop, Nicholas D AU - Gollop ND AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Iwata, Tomoko AU - Iwata T AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Brueckmann, Martina AU - Brueckmann M AUID- ORCID: 0000-0003-1215-0746 AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. AD - Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. FAU - Januzzi, James L AU - Januzzi JL AUID- ORCID: 0000-0002-8338-1798 AD - Massachusetts General Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. AD - Baim Institute for Clinical Research, Boston, MA, USA. FAU - Voors, Adriaan A AU - Voors AA AD - University of Groningen, Groningen, The Netherlands. FAU - Zannad, Faiez AU - Zannad F AUID- ORCID: 0000-0001-7456-1570 AD - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques Plurithematique 1433, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. FAU - Packer, Milton AU - Packer M AD - Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA. AD - Imperial College London, London, UK. LA - eng SI - ClinicalTrials.gov/NCT03057977 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Biomarkers) RN - 0 (Peptide Fragments) RN - 0 (Troponin T) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM CIN - Eur Heart J. 2021 Sep 17;:. PMID: 34534295 MH - Biomarkers MH - *Heart Failure MH - Humans MH - Morbidity MH - Natriuretic Peptide, Brain MH - Peptide Fragments MH - Prognosis MH - Stroke Volume MH - Troponin T PMC - PMC8599073 OTO - NOTNLM OT - Heart failure OT - High-sensitivity cardiac troponin T OT - NT-proBNP OT - Risk score EDAT- 2021/08/24 06:00 MHDA- 2021/11/25 06:00 PMCR- 2021/08/23 CRDT- 2021/08/23 06:45 PHST- 2021/05/31 00:00 [received] PHST- 2021/07/09 00:00 [revised] PHST- 2021/08/11 00:00 [accepted] PHST- 2021/08/24 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2021/08/23 06:45 [entrez] PHST- 2021/08/23 00:00 [pmc-release] AID - 6356321 [pii] AID - ehab579 [pii] AID - 10.1093/eurheartj/ehab579 [doi] PST - ppublish SO - Eur Heart J. 2021 Nov 14;42(43):4455-4464. doi: 10.1093/eurheartj/ehab579.