The Prognostic Value of Neuregulin-1ß in Heart Failure Patients With Preserved Ejection Fraction.

Aim      To determine the neuregulin-1ß concentration in patients with chronic heart failure with preserved ejection fraction (HFpEF) and the association of this biomarker with the functional status of patients, echocardiographic parameters of the structural and functional condition of the heart, and the risk of unfavorable outcome.Material and methods  This observational, prospective study included 47 patients with HFpEF; 32 (68%) of them were females. Mean age was 70 [66-77] years, EF was 57 [56; 58] %. The group of healthy volunteers consisted of 40 people; 32 (55 %) of them were females; mean age was 56 [53-61] years. For all patients, the functional status was evaluated (6-min walk test, 6MWT); standard echocardiography (EchoCG) was performed; and concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and neuregulin-1ß were measured. The follow-up period was two years. Cases of cardiovascular (CV) death and hospitalizations for decompensated chronic heart failure (CHF) were recorded.Results Median concentration of neuregulin-1ß was 0.969 [0.348; 1.932] ng/ml in the HFpEF group, which was significantly higher than 0.379 [0.195; 0.861] ng/ml in the group of healthy volunteers (р=0.003). Significant correlations between the neuregulin-1ß concentration and the distance walked in 6MWT or with EchoCG parameters of left ventricular diastolic function were not found. Mean observation time was 456 [244; 730] days. 21 outcomes were observed, including 2 CV deaths and 19 hospitalizations for CHF. Patients with high concentrations of neuregulin-1ß (≥Me) had a greater frequency of hospitalizations for CHF (Log-rank, p=0.046) and a higher risk of this outcome (risk ratio, 1.30; 95 % confidence interval, 1.01-1.66; p=0.037).Conclusion      Patients with HFpEF had increased concentrations of neuregulin-1ß. High levels of neuregulin-1ß were associated with a higher risk of hospitalization for decompensated CHF.

To study the dynamics of serum levels of vascular remodeling in patients with hypertension, including in combination with type 2 diabetes mellitus during 12­month therapy with perindopril A.

Aim      To study the dynamics of serum markers for vascular remodeling in patients with arterial hypertension (AH), including AH associated with type 2 diabetes mellitus (DM2) during the 12-month treatment with the angiotensin-converting enzyme (ACE) inhibitor, perindopril A.Material and methods  The study included patients with grade 1-2 AH with or without type 2 DM (30 and 32, respectively). Perindopril A 10 mg/day was administered for the outpatient correction of previous, ineffective antihypertensive therapy. The following biomarkers were measured for all patients at baseline and at 12 months: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), E-selectin, endothelin 1, transforming growth factor ß-1 (TGF-ß1), and von Willebrand factor (WF). Laboratory tests were performed with enzyme immunoassay.Results After 12 months of the perindopril A (perindopril arginine) 10 mg/day treatment, both groups achieved the goal blood pressure. Evaluation of biomarker dynamics during the perindopril A treatment showed significant decreases in MMP-9, TIMP-1, and endothelin 1 in the AH group; then the level of TIMP-1 returned to normal values (р<0.05). In the AH+DM2 group, the MMP-9 concentration was significantly decreased (р<0.05); the other values did not show any significant differences. In both groups, MMP-9 was significantly decreased (28.6 % (р=0.01) in group 1 and 33.2 % (р=0.00) in group 2. Notably, in none of these groups, did this index reach normal values. Also, there were no significant differences in this index between the groups (р=0.66). It should be noted that the decreases in TIMP-1 were significantly different between the groups (р=0.001). Thus, this biomarker did not significantly decrease in patients with AH and DM2 (р=0.26) whereas in group 1 (AH without DM2), the level of TIMP-1 decreased by 39.3 % and reached the normal range (р=0.005).Conclusion      Concentrations of biomarkers were decreased in both groups. However, in the AH group, there were statistically significant decreases in the markers that reflect processes of fibrosis and vasoconstriction. At the same time in the AH+DM2 group, there was no significant dynamics of the biomarkers, which was most likely due to more pronounced damage of blood vessels. However, the decrease in MMP-9 may indicate an alleviation of fibrotic processes in arterial walls. These results allow a conclusion that the long-term treatment with the ACE inhibitor, perindopril A, may reverse remodeling of the vascular changes that are called "early vascular ageing".r aging".

[Positive Effects of Perindopril on Microvascular Vessels in Patients With Chronic Heart Failure].

Aim      To evaluate the effect of 12-month perindopril treatment on structure and function of microvasculature (MV) in patients with chronic heart failure with preserved (HFpEF) and intermediate (HFiEF) left ventricular ejection fraction.Material and methods  30 patients with HFpEF and HFiEF were evaluated. Perindopril at a maximum tolerated dose was administered to all patients for 12 months. Changes in MV structure and function were assessed with photoplethysmography and capillaroscopy prior to the treatment onset and at 12 months, i.e., after completion of the perindopril treatment.Results The 12-month perindopril treatment was associated with improvement of the endothelial function evident as increases in the occlusion index (OI) and the phase shift (PS). OI increased from 1.45 [1.3; 1.6] to 1.8 [1.6; 2.2] (p=0.00004). PS increased from 7.1 ms [4.8; 10.2] to 9.2 ms [6.7; 13.2] (p=0.0003). Stiffness of muscular large blood vessels was decreased. Arterial stiffness index (aSI) decreased from 8.8 [6.6; 11.0] to 7.45 [6.5; 9.4] m /s (р=0.01). The perindopril treatment was associated with increased density of the capillary network at rest (р=0.008) and in tests with venous occlusion (р=0.003) and reactive hyperemia (р=0.0003).Conclusion      The study showed an improvement of endothelial function associated with the 12-month perindopril therapy in patients with HFpEF and HFiEF.