Biomarker‐driven prognostic models in chronic heart failure with preserved ejection fraction: the <scp>EMPEROR</scp>–Preserved trial

Pocock, Stuart J.; Ferreira, João Pedro; Packer, Milton; Zannad, Faı̈ez; Filippatos, Gerasimos; Kondo, Toru; McMurray, John J.V.; Solomon, Scott D.; Januzzi, James L.; Iwata, Tomoko; Salsali, Afshin; Butler, Javed; Anker, Stefan D.

doi:10.1002/ejhf.2607

Cited by 32 publications

(46 citation statements)

References 23 publications

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“…A significant increase in the rates of CV death and HF hospitalization was observed across quartiles, with a 5-fold higher number of events between quartiles 1 and 4 in patients randomized to placebo [ 37 ]. Similar results were obtained in another analysis of EMPEROR-Preserved trial, in which patients with both the lowest NT-proBNP and lowest hs-TnT had a primary event (CV death and HF hospitalization) rate of 2.2 per 100 patient-years compared to 19.2 per 100 patient-years in those with highest NT-proBNP and hs-TnT, with a rate ratio of 8.7 [ 70 ]. Finally, treatment with empagliflozin resulted in a beneficial impact on cardiac outcomes independently from the baseline NT-proBNP and hs-TnT levels evaluated [ 37 ].…”

Section: Troponinssupporting

confidence: 82%

Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond

Morfino

Aimo

Castiglione

et al. 2022

JCDD

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Heart failure (HF) is a significant cause of morbidity and mortality worldwide. HF with preserved ejection fraction (HFpEF) is a complex syndrome, often participated by several cardiac and extracardiac conditions, including chronic kidney disease, pulmonary disease, anaemia and advanced age. Circulating biomarkers reflecting pathophysiological pathways involved in HFpEF development and progression may assist clinicians in early diagnosis and management of this condition. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload and in response to activation of neuro-endocrine-immune system. The relevance of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification has been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the value of NPs to guide HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, predicting outcome independently from NPs. In this review, some novel biomarkers are being tested in such clinical scenario, more tightly linked to specific pathophysiological processes of cardiac damage.

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Section: Troponinssupporting

confidence: 82%

Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond

Morfino

Aimo

Castiglione

et al. 2022

JCDD

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“…c‐index, c‐statistic, or area under the curve) for Pocock's models was equal to 0.71 for survival (i.e. all‐cause mortality and cardiovascular death) and 0.75 for the composite endpoint cardiovascular death or heart failure hospitalization 8 . Subsequent external validation of the two multivariable models in the PARAGON‐HF trial showed similar performance 9 .…”

Section: Figurementioning

confidence: 88%

“…In this issue of the Journal, Pocock and colleagues report the development of a multi‐biomarker risk tool that predicts 2‐year survival as well as the composite risk of cardiovascular death or heart failure hospitalization in patients with HFpEF. Pocock and colleagues developed the risk tool with data from the recent Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Preserved Ejection Fraction (EMPEROR‐Preserved) trial, which investigated the effects of empagliflozin among patients with chronic heart failure with left ventricular ejection fractions (LVEF) >40% 8 . After screening 35 candidate variables for the development of their multi‐biomarker tool, NT‐proBNP, hs‐cTnT and several chronic comorbidities such as chronic obstructive pulmonary disease, insulin‐treated diabetes mellitus and anaemia (as defined as haemoglobin <12 g/dl) were selected for model inclusion.…”

Section: Figurementioning

confidence: 99%

Multi‐biomarker approach to predict survival and adverse cardiovascular events among patients with heart failure with preserved ejection fraction

Joury

Razaghizad

Sharma

2022

European J of Heart Fail

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“…Empagliflozin reduced the risk of events across all risk subsets. The derived risk score may help stratifying HFpEF patients in different risk categories 17 …”

Section: Focus On Clinical Trialsmentioning

confidence: 99%

“…The derived risk score may help stratifying HFpEF patients in different risk categories. 17 Several studies showed the prognostic role of heart rate in HF patients. 18 The interplay of resting heart rate and empagliflozin effects was evaluated in EMPEROR-Preserved.…”

mentioning

confidence: 99%

October 2022 at a glance: focus on clinical trials

Tomasoni

Adamo

Metra

2022

European J of Heart Fail

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Assessment of biomarkers is a cornerstone of heart failure (HF) management. [1][2][3][4] A review from the Biomarkers Working Group of the Heart Failure Association summarizes the utility of biomarkers for defining and managing congestion on top of clinical evaluation, haemodynamics, and imaging. 5 The same group also reviewed the use of circulating biomarkers in clinical trials. They may be used as inclusion criteria, as surrogate endpoints, or as safety endpoints. 6 Focus on clinical trials SGLT2 inhibitorsSodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended as foundational therapy for patients with HF and reduced ejection fraction (HFrEF) for their effects on mortality and HF hospitalizations. [7][8][9][10] They also improved quality of life in randomized controlled trials but their effects on exercise capacity, a measurement not changed by neurohormonal modulators, are less studied. 11 In the multicentre randomized double-blind DAPA-VO 2 trial, dapagliflozin, compared with placebo, significantly improved peak oxygen consumption at 1 and 3 months in stable patients with HFrEF. 12 Administration of SGLT2 inhibitors is associated with an initial decline in estimated glomerular filtration rate (eGFR). Changes in eGFR from randomization to week 4 were assessed in the EMPEROR-Reduced trial. On average, empagliflozin induced a leftward shift of the distribution of the initial eGFR changes, i.e. a greater decrease, of -2.5 ml/min/1.73 m 2 versus placebo in patients with HFrEF. 13 The initial mild decline in eGFR was not associated with a higher risk of HF, mortality, or kidney safety events. 13 Similarly, in the EMPULSE trial, including patients hospitalized for acute HF with an eGFR >20 ml/min/1.73 m 2 , empagliflozin caused an initial decline in eGFR of -2 ml/min/1.73 m 2 at day 15 compared to placebo that was no longer evident at day 90. The clinical benefit of empagliflozin was independent of baseline eGFR. 14 Liver dysfunction is a marker of more severe HF and an independent predictor of poor prognosis. 15 In the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, patients with the highest bilirubin tertile had more severe HFrEF

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Biomarker‐driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR–Preserved trial

Cited by 32 publications

References 23 publications

Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond

Biomarkers of HFpEF: Natriuretic Peptides, High-Sensitivity Troponins and Beyond

Multi‐biomarker approach to predict survival and adverse cardiovascular events among patients with heart failure with preserved ejection fraction

October 2022 at a glance: focus on clinical trials

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