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.

Functional Analysis of SCN5A Genetic Variants Associated with Brugada Syndrome.

BACKGROUND: Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia with increased risk of sudden cardiac death. Mutations in gene SCN5A, which encodes the α-subunit of cardiac voltage-gated sodium channel NaV1.5, have been identified in over 20% of patients with BrS. However, only a small fraction of NaV1.5 variants, which are associated with BrS, are characterized in electrophysiological experiments. RESULTS: Here we explored variants V281A and L1582P, which were found in our patients with BrS, and variants F543L and K1419E, which are reportedly associated with BrS. Heterologous expression of the variants in CHO-K1 cells and the Western blot analysis demonstrated that each variant appeared at the cell surface. We further measured sodium current in the whole-cell voltage clamp configuration. Variant F543L produced robust sodium current with a hyperpolarizing shift in the voltage dependence of steady-state fast inactivation. Other variants did not produce detectable sodium currents, indicating a complete loss of function. In a recent cryoEM structure of the hNaV1.5 channel, residues V281, K1419, and L1582 are in close contacts with residues whose mutations are reportedly associated with BrS, indicating functional importance of respective contacts. CONCLUSIONS: Our results support the notion that loss of function of NaV1.5 or decrease of the channel activity is involved in the pathogenesis of BrS.

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.