Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration.

PURPOSE: In a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up. MATERIALS AND METHODS: Twenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012-2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12-36 months after renal denervation. RESULTS: The average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response. CONCLUSIONS: Although the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Value-based approach to blood pressure telemonitoring and remote counseling in hypertensive patients.

PURPOSE: Blood pressure telemonitoring and remote counselling (BPTM) improves blood pressure (BP) control in patients with hypertension (HTN). Studies assessing the efficacy of BPTM from a value-based perspective are lacking. We investigated whether BPTM fits all principles of the value-based approach (clinical and economic effectiveness, improvement in patient-reported outcome/experience measures (PROM/PREM)). MATERIALS AND METHODS: Two hundred and forty ambulatory patients with uncontrolled HTN were randomised in a 2: 1 manner to BPTM (n = 160, mean age 47 y.o.) and usual care (UC, n = 80; 49 y.o.) with baseline and 3-month follow-up clinic visits. BPTM employed a mobile application (for patients) and a desktop version (for clinician), which allowed communication and exchange of medical data. The main outcomes were changes in office and ambulatory systolic (S) BPs, rate of BP control. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were evaluated in economic analysis. The MOS SF-36 score was taken as a PROM, and the PEQ score was used as a PREM. RESULTS: Larger decreases in office and ambulatory SBPs (-16.8 and -8.9 mm Hg, respectively; p < .05) was achieved in BPTM group while the treatment intensity was equal (2.4 drugs). The ICER 11.1 EUR/-1 mm Hg 24-hour SBP/1 year was 75% effective as per willingness-to-pay threshold. BPTM improved PROM (+2.1 in mean MOS SF-36; p = .04), reduced long-term mortality (+0.11 life years gained), leading to +0.49 quality-adjusted life years (QALYs) gained as compared with UC. The ICUR was 4 169.4 EUR/QALY gained. Patient-reported experience was higher in the BPTM (+10 PEQ, p = .01). The UC group showed minor changes in MOS SF-36 and PEQ (+1.3; +6, respectively; p n.s.). CONCLUSIONS: Being cost-effective, BPTM incorporates both clinical benefits and patient-perceived value. Larger randomised studies are needed to confirm our findings.

Acute salt loading and cardiotonic steroids in resistant hypertension.

The study addresses the association of marinobufagenin (MBG), a natriuretic and vasoconstrictor steroid, and Na/K-ATPase (NKA) activity with pressor response to salt-loading and arterial stiffness in resistant hypertension (RH). Thirty-four patients (18 males and 16 females; 56±8 years) with RH on a combined (lisnopril/amlodipine/hydrochlorothiazide) therapy and 11 healthy age-matched normotensive subjects (7 males and 4 females; 54±2 years) were enrolled in this study. Salt-loading was performed via intravenous infusion of 1000mL saline (0.9% NaCl) for 1h. Arterial stiffness was measured by Sphygmocor Px device with a calculation of pulse-wave velocity (PWV). Activity of NKA was measured in erythrocytes. We demonstrated that plasma levels of MBG and magnitude of NaCl-induced MBG-dependent NKA inhibition are associated with PWV, and that this association has gender- and age-specific fashion in RH patients.

DigiFab interacts with endogenous cardiotonic steroids and reverses preeclampsia-induced Na/K-ATPase inhibition.

Elevated levels of endogenous Na/K-ATPase (NKA) inhibitors, cardiotonic steroids (CTSs) including marinobufagenin (MBG), contribute to pathogenesis of preeclampsia (PE) and represent a target for immunoneutralization by Digibind (Ovine Digoxin Immune Antibody, Glaxo-Smith Kline). Because Digibind is no longer commercially available, we studied whether DigiFab (BTG International Ltd, UK) can substitute Digibind for immunoneutralization of CTS in patients with PE. We compared DigiFab, Digibind, and anti-MBG monoclonal antibody (mAb) with respect to their ability to interact with CTS in PE plasma and to restore NKA activity in erythrocytes from patients with PE. Using immunoassays based on DigiFab, Digibind, and anti-MBG mAb, we studied the elution profile of CTS following high-performance liquid chromatography (HPLC) fractionation of PE plasma. Totally, 7 patients with mild PE (28 ± 2 years; gestational age, 39 ± 0.5 weeks; blood pressure 156 ± 5/94 ± 2 mm Hg) and 6 normotensive pregnant participants (28 ± 1 years; gestational age, 39 ± 0.4 weeks; blood pressure 111 ± 2/73 ± 2 mm Hg) were enrolled. Preeclampsia was associated with a substantial inhibition of erythrocyte NKA (1.47 ± 0.17 vs 2.65 ± 0.16 µmol Pi/mL per h in control group, P < .001). Ex vivo, at 10 µg/mL concentration, which is consistent with the clinical dosing of Digibind administered previously in PE, DigiFab and Digibind as well as anti-MBG mAb (0.5 µg/mL) restored erythrocyte NKA activity. Following HPLC fractionation of pooled PE and control plasma, PE-associated increase in CTS material was detected by Digibind (176 vs 75 pmoles), DigiFab (221 vs 70 pmoles), and anti-MBG mAb (1056 vs 421 pmoles). Therefore, because DigiFab interacts with CTS from PE plasma and reverses PE-induced NKA inhibition, it can substitute Digibind for immunoneutralization of CTS in patients with PE.