Effects of different ablation points of renal denervation on the efficacy of resistant hypertension

Patient selection and follow-up

In this retrospective study, all patients who received RDN were above 18 years old and complied with the European Consensus 12. The detailed inclusion criteria were: (1) patients have been treated with three or more antihypertensive drugs, including a diuretic (During the study, there was no change in the treatment of hypertension.); (2) the mean of 24-hour systolic BP>140 mmHg (Calhoun et al., 2008) ; and (3) the estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m² during hospitalization. In addition, patients were excluded if they showed any contraindications to RDN, or displayed any signs of the following conditions: (1) mental illness; (2) pregnancy or contraception; (3) allergic to iodine-containing rays and contrast media; (4) secondary hypertension (renal artery stenosis, coarctation of aorta, hyperaldosteronism, hyperthyroidism and pheochromocytoma); (5) malignant diseases; (6) New York Heart Association class III-IV with congestive heart failure; (7) hypertensive heart failure; (8) chronic renal failure 4–5 (eGFR ≤30 mL/min/1.73 m²); (9) arrhythmia (II degree, III degree atrioventricular block or sinus bradycardia<40 bpm); and (10) valvular disease. Patients were excluded from the study if they had a change in drug use. The study was approved by the Institutional Ethics Committee of Putuo Hospital, Shanghai University of Traditional Chinese Medicine (# 002192).

Ambulatory blood pressure measurement

Ambulatory BP measurement (ABPM) was evaluated with a cuff-based oscillometric device at baseline and 6 months post operation. BP recording was performed every 15 min during the day (7:00 AM to 10:00 PM) and every 30 min during the night (10:00 PM to 7:00 AM) according to the latest European Society of Cardiology guidelines (Calhoun et al., 2008).

Renal denervation

All patients were premedicated by intaking enteric-coated aspirin or 300-mg Clopidogrel hydrogen sulfate tablets. Both renal arteries were ablated using the Symplicity RDN System (Boston Scientific, St. Paul, Minnesota, USA and IBI, St. Jude Medical Systems, Inc.) via transfemoral access. Catheter tip temperature and impedance were monitored during ablation with the temperature fluctuating between 28−35 °C. The energy was between 6–14 W with ablation for 60 s at each point. Depending on the renal artery, the anatomical ablation was performed with a maximum of 16 points in the right and left renal arteries. Pain was relieved by intravenous injection of remifentanil or morphine for all the patients. All procedures were performed by experienced interventional cardiologists.

Safety assessment

The biochemical index, ABPM and transthoracic echocardiography were performed, and eGFR were assessed before RDN and after 6 months for both groups.

Statistical analyses

Quantitative data was presented as mean ± SD and categorical data were presented using counts and percentages. Group comparisons were made by using independent two-sample t-test for continuous data and Chi-square test or Fisher exact test for categorical data, as appropriate. Spearman correlation coefficient was used to evaluate the correlation between parameters. P < 0.05 was considered statistically significant. All data was analyzed using SPSS version 22.0 software (IBM Corp., Armonk, NY, USA).

Baseline characteristics and RDN ablation parameters

Data of 48 cases were examined, of which two cases had missing follow-up due to death, and four cases were excluded due to change in drug use, leading to 42 cases to be included for this study. The baseline characteristics of the patients included in the analysis are presented in Table 1. These 42 patients were divided into two groups according to the numbers of ablation points of RDN (Fig. 1): (1) the standard treatment group (Fig. 1A): spiral ablation from near to proximal, with less than 8 points per artery (adjacent ablation point interval 0.5 cm); ablation energy was 8–10 w, and each ablation point was ablated for 60 s (Krum et al., 2014; Symplicity HTN-2 Investigators et al., 2010; Johns, 2014; Kopp, 2011; Tsioufis et al., 2017); and (2) the intensive treatment group (Fig. 1B): from near to far by spiral ablation, with at least 8 points per artery (adjacent ablation point interval 0.25 cm); ablation energy was 8-10 w, and each ablation point was ablated for 60 s. Except for the ablation points, there was no significant difference in all of the other parameters. The average number of ablation points per patient was 9.1 ± 3.0; the average initial ablation impedance was 184.0 ± 25.1 Ω; the lowest average ablation impedance was 163.1 ± 20.3 Ω; and the range of impedance decline rate was 7.1%–14.4%, with an average of 11.1% ± 5.0%). The actual ablation temperature was between 25−46 °C and the power was between 6–13 W.

Blood pressure

Comparison of 24-hour dynamic systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the standard and the intensive treatment groups showed no significant difference in baseline BP before ablation (Fig. 2A), or 6 months postoperative BP (Fig. 2B). Interestingly, the mean 24-h blood pressure decreased significantly from baseline to 6 months in the intensive treatment group (24–h systolic blood pressure decreased by 27.4 ± 11.4 mmHg, P < 0.0001; 24–h diastolic blood pressure decreased by 10.9 ± 9.6 mmHg, P = 0.005; Fig. 2C).

Correlation between the number of ablation points and mean changes of SBP and DBP after 6 months was analyzed (in mmHg; Fig. 3). The results of the mean 24-h blood pressure showed that the average SBP decline rate increased with the number of ablation points (R² = 0.777, P < 0.01; Fig. 3A). Similar correlation pattern was also observed for DBP (R² = 0.633, P < 0.01; Fig. 3B).

Safety index

Both treatments showed good tolerability and safety in the present study as demonstrated by the safety index parameters, with no significant difference between the two groups (Table 2). Notably, the eGFR remained unaltered 6 months after RDN in both groups. Meanwhile, none of the patients developed acute kidney injury, showed doubling of creatinine, or required dialysis.

Echocardiography

Patients of both groups were assessed for left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), interventricular septum (IVS), fractional shortening (FS), left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP) and heart rate (HR) before and 6 months after RDN (Table 3). None of these values showed significant difference between the two groups at baseline before RDN. LVEF and IVS were slightly improved in the two groups, but there was no statistical difference.

Adverse reactions

During the 6-month follow-up after surgery, 1 (2.4%) participant of the standard treatment experienced cardiovascular disease events or death, and 2 (4.8%) experienced other serious adverse events; while in the intensive treatment group, 3 (7.2%) participants experienced cardiovascular disease events or deaths. There was no significant difference between the two groups in the follow-up of adverse events (Table 4).

Limitations

Admittedly, the present study suffered from several limitations. Firstly, the number of patients enrolled in this study was relatively small, and our study may not have sufficient statistical power. The number of postoperative adverse reactions in the follow-up might be affected due to the small sample size in this study. Secondly, our study was a single-center one and all patients in this study had high BP. Therefore, the results might not be representative of the overall hypertensive population. Finally, the retrospective design was subject to selection bias.