Prognostic roles of obstructive sleep apnea syndrome and right ventricular dysfunction in heart failure patients with preserved ejection

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To study the prognostic roles of obstructive sleep apnea syndrome (OSAS) and right ventricular dysfunction in the development of heart failure (HF) progression in patients with preserved ejection fraction (HFpEF) during the 12-month follow-up period. Methods. The severity of obstructive breathing disorders during sleep was assessed by the apnea/hypopnea index (AHI). A total of 86 men, median age of 62.0 (41.0; 78.0) years with moderate and severe OSAS (with AHI &amp;gt; 15 per hour) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. All patients had the abdominal obesity (WC &amp;gt; 92 cm), body mass index exceeded 30 kg/m2. Serum levels of NT-proBNP were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular function and 6-minute walk test were performed at baseline and at 12 months. Results. At 12 months of follow-up period all patients were divided into 2 groups: group 1 (n = 33) comprised patients with HF progression, group 2 (n = 53) without it. The concentration of NT-proBNP at baseline was higher by 18% in group 1 than in group 2 (p = 0.024; 338 [168; 678] vs. 278 [177; 815] pg/mL, respectively). The median values of AHI (p &amp;lt; 0.0001) were 46.0 [20.6; 85] per hour in group 1 and 24.0 [21.0; 28.0] per hour in group 2. In group 1 than in group 2 fractional change in the area of the right ventricle (ΔSRV) was less by 9.1% (p = 0.031; 40 [35; 47] vs. 44 [40; 47]%, respectively) and right ventricular myocardial function index (RVSWI, Tey index) was less by 8% (p = 0.022; 0.23 [0.22; 0.25] vs. 0.25 [0.24; 0.26], respectively). Based on ROC-analysis, AHI ≥33.5 episodes per hour (sensitivity 75.8%, specificity 67.9%, AUC = 0.732; p &amp;lt; 0.0001), ΔSRV ≤18.6% (sensitivity 75.8%, specificity 54.7%, AUC = 0.62; p = 0.047) and NT-proBNP ≥311 pg/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &amp;lt; 0.0001) were identified as a cut-off values predicting the development of HF progression. The combined evaluation of NT-proBNP and AHI increased the predictive value of the analysis (sensitivity of 82.6%, specificity of 77.1%, and AUС of 0.821; p &amp;lt; 0.0001). Conclusion. Our data suggest that NT-proBNP, AHI and ΔSRV may be used as a diagnostic biomarker for HF progression in patients with preserved ejection fraction (HFpEF) during the 12-month follow-up period. The combined use of NT-proBNP and AHI demonstrated higher diagnostic sensitivity and specificity for prediction of unfavorable course of HF. </jats:sec

Prognostic value of soluble ST2 biomarker in heart failure patients with obstructive sleep apnea syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To analyze the relationships between soluble ST2 (sST2) levels, apnea/hypopnea index (AHI) and echocardiographic parameters in heart failure patients with preserved ejection fraction (HFpEF) and to evaluate prognostic values of sST2 in the development of adverse cardiac events (ASE) during the 12-month follow-up period. Methods. A total of 86 men, median age of 62.0 (41.0; 78.0) years with obstructive sleep apnea syndrome (OSAS) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. The severity of obstructive breathing disorders during sleep was assessed by AHI. Serum levels of NT-proBNP and sST2 were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular (RV) function and 6-minute walk test (6MWT) were performed at baseline. Results. The values of AHI significantly correlated with body mass index (r = 0.362), left atrial volume (r = 0.570), fractional change in the area of the RV (r=-0.527), RV myocardial function index (r=-0.377), NT-proBNP (r = 0.611), 6MWT (r=-0.511), RV anterior wall thickness (r = 0,472), while the levels of sST2 significantly correlated with LV remodeling parameters: LVEF (r =-0.301), end-systolic volume (r =0.453), end-diastolic volume (r =0.396), end-systolic dimension (r = 0.373), end-diastolic dimension (r =0.288). Based on ROC-analysis, sST2 ≥29.67 ng/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &amp;lt; 0.0001) were identified as a cut-off values predicting the development of ACE. At 12 months of follow-up period all patients were divided into 2 groups according to cut-off values of sST2: group 1 (n = 29) comprised patients with sST2 ≥29.67 ng/mL, group 2 (n = 42) comprised patients with sST2 &amp;lt;29.67 ng/mL. The median baseline values of sST2 were 41.39 [33.31; 50.99] ng/mL in group 1, and 22.18 [20.64; 25.5] ng/mL in group 2. The concentrations of NT-proBNP did not differ between the groups. During the 12-month follow-up period in group 1 the rate of ACE was 29.7% cases, and 5.2% in group 2, respectively. According to Kaplan-Meier analysis, a higher sST2 levels was associated with a higher frequency of ACE during 12 months of follow-up (р&amp;lt;0.0001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with ACE (odds ratio 2.25, 95%CI: 2.06 to 3.29, p &amp;lt; 0.001), when adding AHI and LV myocardial mass index improved reclassification of risk stratification (odds ratio 3,28, 95%CI: 3,09 to 4,49, p &amp;lt; 0.001, AUC of 0.945, percent of cases correctly classified of 90.14 %). However, NT-proBNP addition had a limited effect on risk stratification. Conclusion. Our data suggest that sST2 may be used as a diagnostic biomarker for prediction of ACE in patients with HFpEF and OSAS during the 12-month follow-up period. The combined evaluation of sST2, AHI and LV myocardial mass index values demonstrated higher diagnostic sensitivity and specificity for prediction of ACE. </jats:sec

Effect of 24-Week Treatment with Telmisartan on Myocardial Structure and Function: Relationship to Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene

The aim of the present study was to assess the effect of treatment with the angiotensin II receptor blocker telmisartan for 24 weeks on myocardial structure and function in patients with essential hypertension, and the relationship between this effect and the structural polymorphism of the angiotensin-converting enzyme (ACE) gene. Thirty-five patients with essential hypertension and left ventricular hypertrophy (LVH) without other associated morbidity were included in an open-label, non-comparative study. The patients were treated with telmisartan 40-80 mg once daily. In the final analysis, there were 29 patients who received the full course of treatment and were evaluated echocardiographically before and after treatment by the same blinded investigator, and myocardial structure and function were analysed. The myocardial mass of the left ventricle was determined in M-mode. Assessment of diastolic function of transmitral blood flow was performed using pulsed Doppler echocardiography. All patients were genotyped for insertion/deletion (I/D) polymorphism of the ACE gene. Telmisartan produced a significant reduction in left ventricular mass index from 140.4 ± 48.6 to 128.7 ± 40.6 g/m2 that was accompanied by an improvement in characteristics of diastolic function. The decrease in LVH was more significant in the ID genotype group than in the II and DD groups. Thus, prolonged treatment with telmisartan is accompanied by an improvement in myocardial structure, expressed as a reduction in left ventricular mass and function that is more marked in patients with ID genotype of the ACE gene. </jats:p

Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION&ndash;EGF) for targeting brain tumors

Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS), 2AL Polenov Russian Scientific Research Institute of Neurosurgery, 3Research Institute of Highly Pure Biopreparations, 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), 5IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS), St Petersburg, RussiaAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION&ndash;EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION&ndash;EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION&ndash;EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION&ndash;EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION&ndash;EGF conjugates in animals provided receptor-mediated targeted delivery across the blood&ndash;brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P&lt;0.001). SPION&ndash;EGF conjugates provide targeted delivery and efficient magnetic resonance contrast enhancement of EGFR-overexpressing C6 gliomas.Keywords: brain tumor, C6 glioma, magnetic nanoparticles, EGFR, epidermal growth factor, MRI contrast agent, SPIO