The study enrolled 130 patients with chronic heart failure (CHF) of ischemic
origin, stage II AB, NYHA FC II-IV, 88 of them - with sinus rhythm and 42 - with
atrial fibrillation. The patients with sinus rhythm were represented by two groups 58
– with reduced LV EF (HFrEF) and 30 - with preserved LV EF (HFpEF). The groups
of patients were matched in age, sex, height, weight, body surface area.
For the purpose of this work, the peculiarities of the clinical course, structural
and functional remodeling of the heart, assessed by echocardiography, and
biological markers of tubulointerstitial injury (KIM-1, NAG, NGAL) were studied;
treatment programs were compared with evaluation of their efficacy in reducing the
risk of cumulative endpoint in patients with CHF of ischemic origin and
tubulointerstitial injury.
The relationship between the
levels of biological markers of tubulointerstitial injury NGAL, NAG, KIM 1 and the
clinical course of CHF of ischemic origin has been identified for the first time.
For the first time, new scientific data on the pathogenetic role of renal
tubulointerstitial injury biomarkers (NGAL, NAG, KIM-1) in the structural and
functional remodeling of the heart and their influence on the dynamics of the studied
parameters during treatment with mineralocorticoid receptor blockers -
spironolactone and eplerenone, have been obtained.
The possibility of using NGAL as a marker of pathological heart remodeling
in CHF patients has been first proven.10
Scientific data on the peculiarities of renal tubulointerstitial injury, parameters
of structural and functional remodeling of the heart in patients with CHF of ischemic
origin have been supplemented.
The treatment effects of mineralocorticoid receptor blockers - spironolactone
and eplerenone, ACE inhibitors, statins on the clinical course of CHF of ischemic
origin and the nature of changes in the renal tubulointerstitium, structural and
functional remodeling of the heart have been analyzed as well as the ways to reduce
the possible risks caused by side effects of these drugs, namely uptake of their
optimal doses, have been suggested.
An algorithm for differential
diagnosis has been developed and criteria for LV systolic dysfunction in CHF
patients with LV EF within the "gray zone" have been determined allowing a clearer
distribution of patients by phenotypes with reduced or preserved LV EF. An increase
in TEI LV > 0.56 r.u., TEI RV > 0.51 r.u., decrease in systolic index dP / dT ≤ 1000
mmHg/s, systolic velocity of the medial (S med ≤ 7 cm / s) and lateral (S lat ≤ 7 cm
/ s) fibrous ring of the mitral valve, the amplitude of the medial (MAPSE med ≤ 11.7
cm) and lateral (MAPSE lat ≤ 11.1 cm) fibrous ring of the mitral valve should be
regarded as criteria for severe systolic dysfunction corresponding to LV EF < 40%.
In the presence of two or more additional criteria for systolic LV dysfunction, CHF
patients with LV EF in the range of 40-55% should be managed as those with
reduced LV EF.
The measurement of NGAL serum concentration has been implemented into
clinical practice to improve the diagnosis of tubulointerstitial injury in patients with
CHF of ischemic origin, regardless of the phenotype. A new diagnostic criterion for
tubulointerstitial injury in CHF patients has been proposed - an increase in serum
NGAL more than 168 ng / ml (the area under the ROC curve 0.505; 95% CI 0.361-
0.648; p = 0.964), sensitivity 81.8%, specificity 32.5%. Furthermore, serum NGAL
should be considered not only as a marker of tubulointerstitial injury in CHF
patients, but also as a marker of pathological heart remodeling.11
It has been proposed to measure the plasma sodium concentration when
choosing the tactics of diuretic therapy. The risk of adverse course of CHF,
regardless of the phenotype, has been shown to be 1.22 times significantly increased
in patients with a decreased sodium level ≤ 142.5 mmol / l.
It has been recommended to identify the following factors: age, body weight,
TEI index, transmitral pressure gradient and maximum blood flow velocity in the
aorta, which can be used for an unfavorable three-year prognosis screening in CHF
patients. A combined impact of factors such as age over 66 years (p = 0.0172), body
weight exceeding 82 kg (p = 0.036), index TEI LV over 0.52 r.u. (p = 0,033), peak
mitral valve pressure gradient over 1.9 mmHg. (p = 0.029), the maximum flow
velocity in the aorta more than 98 cm/sec (p= 0.0014), was associated with an
increase in the relative risk of adverse cardiovascular events, regardless of sex,
glomerular filtration rate and tubulointerstitial injury.
