Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Determination of the total antioxidant capacity of the Chinese tea based on a novel "peroxidase/zirconium phosphonate"composite electrochemical sensor.

In this work, a novel zirconium phosphonate (ZrPR1R2) was prepared by decorating both the aminoethoxy- group (R1) and the carboxypropyl- group (R2) on the zirconium phosphate layers in order to manipulate further the immobilization of the peroxidase (POD), and an antioxidant biosensor with higher sensitivity was constructed by dropping the POD/ZrPR1R2 composite onto the glassy carbon electrode surface. The activity of the POD/ZrPR1R2 composite was detected by Uv-vis spectra. The direct electrochemical behavior, the electrocatalytic response to dissolved oxygen and hydrogen peroxide, as well as the ability to detect total antioxidant capacity in tea sample were investigated by the methods of cyclic voltammetry. The results indicated that the immobilization of POD in ZrPR1R2 nanosheets matrix enhanced the enzymatic activity, and achieved the fast and direct electron transfer between POD and glassy carbon electrode. Moreover, the POD/ZrPR1R2 composite modified electrode show the electrocatalytic response to hydrogen peroxide in the linear range of 8.8×10-8 to 8.8×10-7 mol L-1, with the detection limit of 3.3×10-8 mol L-1. Attributing to the sensitive response to dissolved oxygen, the total antioxidant capacity can be detected directly in the real tea water by this POD/ZrPR1R2 composite modified electrode.

Sympathectomy versus conventional treatment for refractory coronary artery spasm.

BACKGROUND: There is no clear consensus on the potential efficacy and indications for sympathectomy to prevent recurrence of vasospasm in patients with refractory coronary artery spasm (CAS). OBJECTIVE: To compare the clinical outcomes of sympathectomy with those of conventional treatment in patients with refractory CAS. PATIENTS AND METHODS: Patients with refractory CAS were randomly assigned to sympathectomy group (n = 37) or conventional treatment group (n = 42). The primary end point was a composite of major adverse cardiac event (MACE) episodes (including cardiac death, nonfatal myocardial infarction, unstable angina, heart failure, and life-threatening arrhythmia), and the secondary end point was death from any cause within 24 months after randomization. RESULTS: During the follow-up period of 24 months, the incidence of MACE in the sympathectomy and conventional treatment groups was 16.22 and 61.90%, respectively (P = 0.0001). All-cause death as the secondary end point occurred in zero and six (14.29%) patients, respectively (P = 0.0272). The Kaplan-Meier curve for MACE and all-cause death showed a significant between-group difference (log-rank test, P = 0.0013 and 0.0176, respectively). CONCLUSION: Compared with conventional treatment, sympathectomy significantly reduced the composite end point of MACE episodes and death from any cause in patients with refractory CAS by effectively preventing recurrence of vasospasm.

[The effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI].

OBJECTIVE: To assess the safety and effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI. METHODS: A total of 92 patients with ACS post successful PCI were randomly divided into atorvastatin 10 mg/d (group A) and atorvastatin 40 mg/d (group B) on top of the standard medical therapy. Blood were taken at baseline, 4, 12 and 24 weeks for serum alanine aminotransferase (ALT), lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloprotease-9 (MMP-9) measurements. The major adverse cardiac events (MACE) were also observed. RESULTS: There was no significant difference in medication withdrawn (2 vs. 3 cases) due to increased ALT (3 times higher than normal) and incidence of MACE (5 vs. 7 cases) between the groups. TC and LDL were significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 24 weeks post medication (P < 0.05) while TG and HDL remained unchanged. hs-CRP was significantly reduced at 12 and 24 weeks in both groups compared to baseline and the reduction was more significant in group B than that in group A at 24 weeks. MMP-9 was significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 12 weeks post medication (P < 0.05). CONCLUSION: Both atorvastatin doses significantly reduced TC, LDL, hs-CRP and MMP-9 in ACS patients post PCI and the reduction was more significant in high dose atorvastatin group at 24 weeks while the MACE and drug withdraw rates were similar between the groups.