endothelin-1 and Heart-Failure--Diastolic

Diastole plays a central role in cardiovascular homeostasis. Its two main determinants, myocardial relaxation and passive properties of the ventricular wall, are nowadays regarded as physiological mechanisms susceptible of active modulation. Furthermore, diastolic dysfunction and heart failure with normal ejection fraction (previously called diastolic heart failure) are two subjects of major clinical relevance and an intense area of research. The role of several neurohumoral mediators like angiotensin-II and endothelin-1 on the modulation of diastolic function was systematically described as having only chronic deleterious effects such as cardiac hypertrophy and fibrosis. However, over the last years a growing body of evidence described a new role for several peptides on the acute modulation of diastolic function. In the acute setting, some of these mediators may have the potential to induce an adaptive cardiac response. In this review, we describe the role of angiotensin-II, endothelin-1, nitric oxide, urotensin-II and ghrelin on the acute modulation of diastolic function, emphasizing its pathophysiological relevance. Only a thorough understanding of diastolic physiology as well as its active modulation, both in the acute and chronic settings, will improve our knowledge on diastolic dysfunction and allow us to solve the enigmas of heart failure with normal ejection fraction.

Topics: Angiotensin II; Animals; Diastole; Endothelin-1; Ghrelin; Heart Failure, Diastolic; Humans; Myocardial Contraction; Neurotransmitter Agents; Nitric Oxide; Urotensins

The role of biomarkers in asymptomatic diastolic dysfunction (DD) has not been investigated so far. The aim of the study was to evaluate the clinical associations and the diagnostic property of different biomarkers in patients with asymptomatic DD.. Within a population based observational study, healthy participants (50-85 years) with an LVEF ≥ 50 % and no cardiovascular risk factor were prospectively identified. Patients were classified as having either DD (grade ≥ 1, n = 103) or no DD (CON: n = 85). All patients underwent physical examination including medical history, six-minute-walk-testing, QoL (SF-36), comprehensive echocardiography and blood sampling to measure routine values and specified biomarkers (NTproBNP, MRproANP, GDF-15, MRproADM, CTproET1, CTproAVP).. In the DD-group plasma concentration of GDF-15 (p = 0,002), MRproADM (p < 0,001), and CTproAVP (p = 0,003) were significantly higher than in the CON-group. In contrast, NTproBNP (p = 0,390), MRproANP (p = 287), and CTproET1 (p = 0,393) did not differ. GDF-15, MRproADM and CTproAVP were significantly associated with the presence of DD. However, the significance of the seen associations was lost after multiple adjustments. NTproBNP, MRproANP, and MRproADM were significantly related to E / e' as a continuous measure of diastolic function. The significance of the seen associations was lost after multiple adjustments. In ROC analyses, none of the investigated biomarkers was able to relevantly improve the diagnosis of DD.. In patients with asymptomatic DD plasma concentrations of GDF-15, MRproADM and CT-proAVP were significantly higher when compared with controls. In contrast, NTproBNP, MRproANP and CTproET1 did not differ. After adjustment for age, sex, BMI and renal function, no significant association between DD or E / e' and different biomarkers could be observed. Furthermore, none of the investigated biomarkers was able to substantially improve the diagnosis of DD.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Cardiac Output, Low; Endothelin-1; Female; Glycopeptides; Growth Differentiation Factor 15; Heart Failure, Diastolic; Humans; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Reference Values; Risk Factors