Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction

Wijk, Sandra Sanders‐van; Empel, Vanessa van; Davarzani, Nasser; Maeder, Micha T.; Handschin, Rolf; Pfisterer, Matthias; Rocca, H. P. Brunner-La

doi:10.1002/ejhf.414

Cited by 220 publications

(186 citation statements)

References 41 publications

(51 reference statements)

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“…More recently, the contribution of a pro‐inflammatory state to the pathophysiology of HFpEF has been emphasized 6, 8, 17, 23, 31, 34, 35, 36, 45. In patients with ADHF, biomarkers reflecting activation of the renin‐angiotensin aldosterone system (RAAS) (plasma renin activity, aldosterone levels), oxidative stress (uric acid) and collagen synthesis (N‐terminal procollagen III) appear to be elevated to a similar extent in HFrEF and HFpEF 33.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, there has been an effort to better characterize biomarkers in HF with preserved EF (HFpEF)2, 9, 31, 32). While inflammation plays a role in both HFpEF and HFrEF,33 there appear to be distinct differences in their pathogenesis 2, 34, 35, 36. We are unaware of any data in regard to whether more intense inflammation plays a role in acutely decompensated HFpEF (AD‐HFpEF).…”

Section: Introductionmentioning

confidence: 99%

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Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

Abernethy

Raza

Sun

et al. 2018

JAHA

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BackgroundUnderlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro‐inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD‐HFpEF) compared with patients with stable HFpEF (S‐HFpEF).Methods and ResultsUsing a post hoc analysis the serum biomarkers tumor necrosis factor‐alpha, high‐sensitivity C‐reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic‐Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD‐HFpEF or S‐HFpEF. Compared to S‐HFpEF, AD‐HFpEF patients had higher levels of PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin‐6 (4.14 pg/mL versus 1.71 pg/mL, P<0.0001), tumor necrosis factor‐alpha (11.54 pg/mL versus 8.62 pg/mL, P=0.0015), and high‐sensitivity C‐reactive protein (11.90 mg/dL versus 3.42 mg/dL, P<0.0001). Moreover, high‐sensitivity C‐reactive protein, interleukin‐6 and PTX3 levels were significantly higher in AD‐HFpEF compared with S‐HFpEF patients admitted for decompensated HF within the previous year. PTX3 was positively correlated with left atrial volume index (r=0.41, P=0.0017) and left ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor‐alpha was inversely correlated with E/A ratio (r=−0.31, P=0.0395).ConclusionsLevels of pro‐inflammatory biomarkers are strikingly higher in AD‐HFpEF compared with S‐HFpEF patients. PTX3 and tumor necrosis factor‐alpha are correlated with echocardiographic‐Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro‐inflammatory state has a pathophysiologic role in the development of AD‐HFpEF.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

Abernethy

Raza

Sun

et al. 2018

JAHA

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“…While ≈50% of HF patients are HFpEF17 and the mortality rate is similar to those with HFrEF, the neurohormonal activation and pathophysiological heterogeneity indeed are different between the phenotypes of HF 18. Therefore, the prediction model might vary.…”

Section: Discussionmentioning

confidence: 99%

Performance of AHEAD Score in an Asian Cohort of Acute Heart Failure With Either Preserved or Reduced Left Ventricular Systolic Function

Chen

Sung

Cheng

et al. 2017

JAHA

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Background AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes of acute heart failure. However, the prognostic value of the AHEAD score in acute heart failure patients with either reduced or preserved left ventricular ejection fraction (HFrEF and HFpEF) remain to be elucidated.Methods and ResultsThe study population consisted of 2143 patients (age 77±12 years, 68% men, 38% HFrEF) hospitalized primarily for acute heart failure with a median follow‐up of 23.75 months. The performance of the AHEAD score (atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus) was evaluated by Cox's regression analysis for predicting cardiovascular and all‐cause mortality. The mean AHEAD scores were 2.7±1.2 in the total study population, 2.6±1.3 in the HFrEF group, and 2.7±1.1 in the HFpEF group. After accounting for sex, sodium, uric acid, and medications, the AHEAD score remained significantly associated with all‐cause and cardiovascular mortality (hazard ratio and 95% CI: 1.49, 1.38–1.60 and 1.48, 1.33–1.64), respectively. The associations of AHEAD score with mortality remained significant in the subgroups of HFrEF (1.63, 1.47–1.82) and HFpEF (1.34, 1.22–1.48). Moreover, when we calculated a new AHEAD‐U score by considering uric acid (>8.6 mg/dL) in addition to the AHEAD score, the net reclassification was improved by 19.7% and 20.1% for predicting all‐cause and cardiovascular mortality, respectively.ConclusionsThe AHEAD score was useful in predicting long‐term mortality in the Asian acute heart failure cohort with either HFrEF or HFpEF. The new AHEAD‐U score may further improve risk stratification.

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“…Levels of hsTnT have been demonstrated to be higher in HFrEF than HFpEF [59]. This may be due to a greater degree of myocardial damage and loss of HFrEF versus a predominant myocardial hypertrophy and fibrosis in HFpEF.…”

Section: Novel Biomarkersmentioning

confidence: 98%

Clinical Application of Biomarkers in Heart Failure with a Preserved Ejection Fraction: A Review

et al. 2016

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Heart failure with a preserved ejection fraction (HFpEF) is increasingly prevalent and a leading cause of morbidity and mortality worldwide. HFpEF has a complex pathophysiology, with recent evidence suggesting that an interaction of cardiovascular and noncardiovascular comorbidities (e.g. obesity, hypertension, diabetes, coronary artery disease, and chronic kidney disease) induces an inflammatory state that eventually leads to myocardial structural and functional alterations. Current ACCF/AHA guidelines suggest incorporation of biomarkers along with clinical and imaging tools to establish the diagnosis and disease severity in heart failure (HF). However, the majority of data on biomarkers relating to their levels, or their role in accurate diagnosis, prognostication, and disease activity, has been derived from studies in undifferentiated HF or HF with a reduced EF (HFrEF). As the understanding of the mechanisms underlying HFpEF continues to evolve, biomarkers reflecting different pathways including neurohormonal activation, myocardial injury, inflammation, and fibrosis have a clinical utility beyond the diagnostic scope. Accordingly, in this review article we describe the various established and novel plasma biomarkers and their emerging value in diagnosis, prognosis, response, and guiding of targeted therapy in patients with HFpEF.

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Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction

Cited by 220 publications

References 41 publications

Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

Performance of AHEAD Score in an Asian Cohort of Acute Heart Failure With Either Preserved or Reduced Left Ventricular Systolic Function

Clinical Application of Biomarkers in Heart Failure with a Preserved Ejection Fraction: A Review

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