Renal hemodynamics in patients with resistant hypertension and type 2 diabetes mellitus.

Aim    To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods    This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results    Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p<0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p<0.001), increases in concentrations of hsCRP (r=0.35, p<0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p<0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p<0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR <60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion    In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).

[A case of clinically malignant rapid-progressive cardiac myxoma after COVID-19 infection].

This article presents a clinical case of urgent, life-saving surgical intervention in a 69-year-old woman with left atrial myxoma with rapid morphological and clinical progression and a history of COVID-19 and breast cancer in remission. However, the concurrent (perhaps secondary) thrombophilic condition facilitated the complication development in the form of superior vena caval orifice thrombosis in the early postoperative period. For this complication, repeated surgery in the volume of thrombectomy was performed, which resulted in stabilization of the patient's condition.

Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction In Patients With Resistant Hypertension and Type 2 Diabetes Mellitus.

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabolic, proinflammatory and profibrotic biomarkers, increased vascular wall stiffness, pronounced left ventricular hypertrophy, and with structural and functional alterations in kidneys.

Erythrocyte membranes beta-adrenoreactivity changes after renal denervation in patients with resistant hypertension, relationship with antihypertensive and cardioprotective intervention efficacy.

Aim      To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment.Material and methods  The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity.Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= -0.54; р<0.05) and with left ventricular myocardial mass (LVMM) (r= -0.36; р<0.05) at two years of follow-up whereas beta-ARM delta at one week was interrelated with the renin concentration in the long-term (r= -0.44; р<0.05). At two years, the content of beta-ARM was increased in both groups.Conclusion      The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

Refractory and Resistant Hypertension in Patients with Type 2 Diabetes Mellitus: Different Response to Renal Denervation.

Aim      To compare the antihypertensive effectivity of renal denervation in patients with diabetes mellitus (DM) and associated refractory arterial hypertension (rfAH) (treated with 5 or more classes of antihypertensive drugs, including a thiazide diuretic and a mineralocorticoid receptor antagonist) and uncontrolled resistant AH (ucAH) (treated with 3-4 drugs).Material and methods  This interventional study with renal denervation included 18 DM patients with rfAH and 40 DM patients with ucAH; 16 and 36 of them, respectively, completed the study in 6 months. At baseline, patients were sex- and age-matched. Study methods included measurement of office blood pressure (BP; systolic/diastolic BP, SBP/DBP); outpatient BP monitoring; evaluation of kidney function (estimated glomerular filtration rate by the CKD-EPI formula); diurnal diuresis volume; diurnal urinary excretion of albumin, potassium and sodium; diurnal excretion of metanephrines and normetanephrines; and plasma levels of glucose and glycated hemoglobin, aldosterone, and active renin. Patients were instructed about maintaining compliance with their antihypertensive and hypoglycemic therapy throughout the study.Results At baseline, patients of both groups were comparable by BP and major clinical indexes, except for higher values of nocturnal SBP variability (p<0.05) in patients with rfAH. At 6 months following renal denervation, both groups displayed significant decreases in office and average daily SBP and also in the "load" with increased mean diurnal SBP. However, the decrease in average daily SBP was almost 4 times greater in the rfAH group than in the ucAH group ( -19.9 and -5.1 mm Hg, respectively, р=0.02). Moreover, 81 % of patients in the rfAH group responded to the intervention (average daily SBP decrease ≥10 mm Hg) while the number of responders in the ucAH group was considerably smaller (42 %; p=0.02). In patients with rfAH, renal denervation was associated with a significant decrease in pulse BP and nocturnal SBP variability and with the increase in diurnal diuresis. No other alterations were noted in laboratory test results in either group.Conclusion      DM patients with rfAH may be the best candidates for the procedure of renal denervation.

[Criteria for selecting patients with resistant hypertension for a renal sympathetic denervation]. / Kriterii otbora bol'nykh s rezistentnoi arterial'noi gipertoniei dlya simpaticheskoi denervatsiya pochek.

AIM: to define and develop a procedure that can select patients with resistant hypertension (RH) for a renal sympathetic denervation (RSD) procedure, by being orienting to the specific initial values of ß-adrenoreactivity (ß-AR) and systolic blood pressure (SBP). SUBJECTS AND METHODS: The analysis included 23 RH patients receiving the maximally tolerable doses of 4 antihypertensive drugs. The investigations involving BP control and a Russian spectrophotometric procedure for determining ß-AR in terms of the change in the osmoresistance of erythrocyte membranes (EM) were performed at baseline and 4 and 24 weeks. RSD was carried out using endovascular radiofrequency ablation of the renal arteries. The therapy was not changed during the observation. RESULTS: If SBP was >170 mm Hg and ß-AR of EM >40 conditional units (CUs) at baseline, ΔSBP was 17.68±3.24 mm Hg and the efficiency of RSD was 100%. When SBP was <170 mm Hg and ß-AR of EM <40 CUs at baseline, ΔSBP was 0.97±4.21 mm Hg (p>0.05) and the efficiency of RSD was low. CONCLUSION: The overall estimate of baseline SBP and ß-AR of EM in patients with RH could determine the expediency of the RSD procedure in order to lower BP. The proposed procedure can optimize the selection of patients and enhance the efficiency of RSD in the treatment of RH.