Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure)

Stienen, Susan; Ferreira, João Pedro; Kobayashi, Masatake; Preud’homme, Gregoire; Dobre, Daniela; Machu, Jean‐Loup; Duarte, Kévin; Bresso, Emmanuel; Devignes, Marie‐Dominique; López, Natalia; Girerd, Nicolas; Aakhus, Svend; Ambrosio, Giuseppe; Rocca, Hans‐Peter Brunner‐La; Fontes‐Carvalho, Ricardo; Fraser, Alan G.; Heerebeek, Loek van; Heymans, Stéphane; Keulenaer, Gilles W. De; Marino, Paolo; McDonald, Kenneth; Mebazaa, Alexandre; Papp, Zoltán; Raddino, Riccardo; Tschöpe, Carsten; Paulus, Walter J.; Zannad, Faı̈ez; Rossignol, Patrick

doi:10.1080/1354750x.2020.1727015

Cited by 32 publications

(33 citation statements)

References 86 publications

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“…In MEDIA-DHF, a multicenter, multinational, observational study, a total of 626 HFpEF patients were enrolled between 2012 and 2014 in 10 centers (listed in Supplemental table 1). A description of this study population and methods has been published previously [7]. To summarize, after standardized echocardiography (Supplemental data) and/or local natriuretic peptide measurements, eligible patients with a diagnosis of diastolic dysfunction as established by the 2007 ESC recommendations [8] were included.…”

Section: Study Populationmentioning

confidence: 99%

“…The association between sex and the composite endpoint of CV death or CV hospitalizations within 1 year after inclusion in the study was studied using Kaplan-Meier estimates and Cox proportional hazards models. In multivariate analyses, adjustment was performed for clinical variables previously found to be independently associated with CV death or CV hospitalizations in MEDIA-DHF [7]. These clinical variables were a history of CAD, pulmonary rales at baseline, and age.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…Hydrolyses angiotensin I and angiotensin II generating angiotensin (1)(2)(3)(4)(5)(6)(7)(8)(9) and angiotensin [1][2][3][4][5], respectively.…”

Section: Ace2mentioning

confidence: 99%

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Sex differences in circulating proteins in heart failure with preserved ejection fraction

et al. 2020

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Background: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18. Conclusion: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

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Section: Study Populationmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

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Sex differences in circulating proteins in heart failure with preserved ejection fraction

et al. 2020

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“…We speculated that detailed echocardiographic phenotyping of well‐characterized patients with HFpEF could yield parameters that correlate with natriuretic peptides and be associated with hospitalization and death from cardiovascular causes. This hypothesis was tested in the prospective cohort of the European MEtabolic Road to DIAstolic Heart Failure (MEDIA) project 18 . We validated out findings in the Swedish–French KaRen HFpEF cohort 19 …”

Section: Introductionmentioning

confidence: 66%

Risk stratification with echocardiographic biomarkers in heart failure with preserved ejection fraction: the media echo score

Huttin¹,

Fraser

Lund

et al. 2021

ESC Heart Failure

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Aims Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort. Methods and resultsWe assessed the association between echocardiographic parameters and cardiovascular outcomes in 515 patients with heart failure with preserved left ventricular (LV) ejection fraction (>50%) in the MEtabolic Road to DIAstolic Heart Failure (MEDIA) multicentre study. We validated out findings in 286 patients from the Karolinska-Rennes Prospective Study of HFpEF (KaRen). After multiple adjustments including N-terminal pro-brain natriuretic peptide (NT-proBNP), the significant predictors of death or cardiovascular hospitalization were pulmonary arterial systolic pressure > 40 mmHg, respiratory variation in inferior vena cava diameter > 0.5, E/e' > 9, and lateral mitral annular s' < 7 cm/s. The combination of these four variables differentiated patients with <10% vs. >35% 1 year risk. Adding these four echocardiographic variables on top of clinical variables and NT-proBNP yielded significant net reclassification improvement (33.8%, P < 0.0001) and increase in C-index (5.3%, a change from 72.2% to 77.5%, P = 0.015) of similar magnitude as the addition of NT-proBNP on top of clinical variables alone. In the KaRen cohort, these four variables yielded a similar improvement in net reclassification improvement (22.3%, P = 0.014) and C-index (4.0%, P = 0.029). Conclusions Use of four simple echocardiographic parameters (within the MEDIA echo score), indicative of pulmonary hypertension, elevated central venous pressure, LV diastolic dysfunction, and LV long-axis systolic dysfunction, independently predicted prognosis and improved risk stratification additionally to clinical variables and NT-proBNP in HFpEF. This finding was validated in an independent cohort.

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“…Therefore, patients' history, associated risk factors, comorbidities, body size conformation, and response to therapy should be taken into account beyond the simple EF calculation (42). The real challenge is to concretize and combine several epidemiological, biohumoral, mechanistic, and cardiac functional data across a spectrum of different phenotypes in which each subject has a specific HF onset, development, and pathophysiological pathways (43). Indeed, the population included in the HFmrEF category is extremely variable, encompassing patients with different disease triggers, demographic characteristics, associated diseases, and mortality risks (Figure 1).…”

Section: Limitations Related To Ef Assessmentmentioning

confidence: 99%

Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes

Palazzuoli

Beltrami

2021

Front. Cardiovasc. Med.

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Traditionally, patients with heart failure (HF) are divided according to ejection fraction (EF) threshold more or <50%. In 2016, the ESC guidelines introduced a new subgroup of HF patients including those subjects with EF ranging between 40 and 49% called heart failure with midrange EF (HFmrEF). This group is poorly represented in clinical trials, and it includes both patients with previous HFrEF having a good response to therapy and subjects with initial preserved EF appearance in which systolic function has been impaired. The categorization according to EF has recently been questioned because this variable is not really a representative of the myocardial contractile function and it could vary in relation to different hemodynamic conditions. Therefore, EF could significantly change over a short-term period and its measurement depends on the scan time course. Finally, although EF is widely recognized and measured worldwide, it has significant interobserver variability even in the most accredited echo laboratories. These assumptions imply that the same patient evaluated in different periods or by different physicians could be classified as HFmrEF or HFpEF. Thus, the two HF subtypes probably subtend different responses to the underlying pathophysiological mechanisms. Similarly, the adaptation to hemodynamic stimuli and to metabolic alterations could be different for different HF stages and periods. In this review, we analyze similarities and dissimilarities and we hypothesize that clinical and morphological characteristics of the two syndromes are not so discordant.

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Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure)

Cited by 32 publications

References 86 publications

Sex differences in circulating proteins in heart failure with preserved ejection fraction

Sex differences in circulating proteins in heart failure with preserved ejection fraction

Risk stratification with echocardiographic biomarkers in heart failure with preserved ejection fraction: the media echo score

Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes

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