Abstract
Objectives:
Renal denervation (RDN) has been proven to be effective in lowering blood pressure (BP) in patients, but previous studies have had short follow-ups and have not examined the effects of RDN on major cardiovascular outcomes. This study aimed to demonstrate the effectiveness and safety of RDN in the long-term treatment of hypertension and to determine if it has an effect on cardiovascular outcomes.
Methods:
All patients with resistant hypertension who underwent RDN between 2011 and 2015 at Tianjin First Central Hospital were included in the study. Patients were followed up at 1,5 and 10 years and the longest follow-up was 12 years. Data were collected on office BP, home BP, ambulatory BP monitoring (ABPM), renal function, antihypertensive drug regimen, major adverse events (including acute myocardial infarction, stroke, cardiovascular death and all cause death) and safety events.
Results:
A total of 60 participants with mean age 50.37 ± 15.19 years (43.33% female individuals) completed long-term follow-up investigations with a mean of 10.02 ± 1.72 years post-RDN. Baseline office SBP and DBP were 179.08 ± 22.05 and 101.17 ± 16.57 mmHg under a mean number of 4.22 ± 1.09 defined daily doses (DDD), with a reduction of −35.93/−14.76 mmHg as compared with baseline estimates (P < 0.0001). Compared with baseline, ambulatory SBP and DBP after 10-years follow-up were reduced by 14.31 ± 10.18 (P < 0.001) and 9 ± 4.35 (P < 0.001) mmHg, respectively. In comparison to baseline, participants were taking fewer antihypertensive medications (P < 0.001), and their mean heart rate had decreased (P < 0.001). Changes in renal function, as assessed by estimated glomerular filtration rate (eGFR) and creatinine, were within the expected rate of age-related decline. No major adverse events related to the RDN procedure were observed in long-term consequences. All-cause mortality and cardiovascular mortality rates were 10 and 8.34%, respectively, for the 10-year period.
Conclusion:
The BP-lowering effect of RDN was safely sustained for at least 10 years post-procedure. More importantly, to the best of my knowledge, this is the first study to explore cardiovascular and all-cause mortality at 10 years after RDN.
Keywords: blood pressure, hypertension, renal denervation, renal function
INTRODUCTION
Hypertension is one of the most common modifiable risk factors for cardiovascular events worldwide. Despite multiple pharmacologic and nonpharmacologic options for managing hypertension, most patients do not achieve the blood pressure (BP) goals presented in modern guidelines. It has been demonstrated that RDN significantly lowers BP in hypertensive patients by inhibiting the activity of afferents and efferent sympathetic nerves. Previous studies, regardless of the ablation modality, confirming both the BP (BP)-lowering efficacy and safety of RDN in a broad range of patients with hypertension, including resistant hypertension [1–4]. Expert consensus in multiple countries and regions has proposed that RDN can be used as an adjunct treatment option for uncontrolled and resistant hypertension despite best efforts at lifestyle and pharmacologic interventions [5,6]. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long-term [7]. However, there are limited data on the long-term safety and efficacy of RDN. In addition, there are no reliable clinical or biochemical factors that can be applied to predict the success of the procedure, and which type of hypertensive patients would benefit most from RDN treatment. Hence, the purpose of this study was to identify which hypertensive patients may be candidates for RDN through a long-term follow-up.
Despite the strong association between hypertension and cardiovascular risk, the effect of RDN on cardiovascular outcomes remains unclear. In addition, there are no studies on the effect of RDN on major adverse events, including acute myocardial infarction, stroke, cardiovascular death, and all-cause mortality, in hypertensive patients. We, therefore, sought to determine whether RDN reduces the incidence of major adverse cardiovascular events in patients with resistant hypertension over the long-term.
METHODS
Study design and population
This single-center, single-arm real-world study was conducted at Tianjin First Central Hospital. Patients aged 18–80 years with resistant hypertension or inability to tolerate multiple antihypertensive drugs were enrolled in the study. Inclusion criteria were seated office SBP (averaged over three measurements) over 160 mmHg or more at screening. Exclusion criteria were secondary hypertension, abnormal renal artery anatomy, estimated glomerular filtration rate (eGFR) less than 45 ml/min/1.73 m2. Eligible patients who underwent percutaneous renal denervation (RDN) at Tianjin First Central Hospital from 2011 to 2015 were included. Baseline demographics of the patients, the number and dose of anti-hypertensive drugs used before and after RDN were recorded. Changes in office BP (OBP), home BP (HBP), ambulatory BP monitoring (ABPM), and the number of antihypertensive drugs were used to evaluate the efficacy. Safety endpoints were the change in renal function measured by eGFR.
Primary endpoint events included: acute coronary syndrome, stroke, end-stage renal disease, and cardiovascular death; secondary endpoint events included: all-cause death. The study protocol is in accordance with the Helsinki Declaration on Ethical Guidelines, and all patients provided written informed consent to participate.
Renal denervation procedure
The patients underwent bilateral renal arteriography via femoral (n = 39) or brachial (n = 21) access to confirm anatomic eligibility. A 6F standard electrophysiology catheter (CELSIUS, Biosense Webster, USA) connected to radiofrequency equipment (IBI-1500T, the United States IBI company) was inserted into each renal artery and 6–12 ablations were carried out at 8–12 W for 2 min on each side. During the ablation process, the temperature and resistance of the catheter tip were monitored. Fentanyl citrate and morphine were used to relieve visceral pain. The renal arteriography was finally reviewed to exclude operative complications. All patients were discharged on aspirin for at least 3 months.
Blood pressure measurement
In brief, office SBP and DBP measurements were assessed with the Omron automatic blood pressure monitor (M10-IT, Omron Healthcare, Bannockburn, Illinois, USA). The same arm for each patient was used for the screening and all subsequent follow-up visits to assess BP. Seated office BP and HBP were measured with the same validated electronic device [M10-IT (Omron Healthcare)].
Patients were followed at in-office or telephone visits at 1, 5 and 10 years post-RDN per standard of care. Office BP was measured at discharge and follow-up according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure guidelines [8]. In addition to follow-up of office BP, patients were instructed to perform regular home blood-pressure self-measurements. A minimum of three BP recordings per measurement period was required for a valid measurement of the home SBP average.
Ambulatory blood pressure monitoring
A 24-h ABPM was obtained using an oscillometric cuff (Oscar 2, SunTech, USA), completed by 40, 29 and 16 participants at baseline, 1 year and 10 years after the RDN, respectively. The ABPM continuously monitored the SBP, mean BP (MAP), DBP, and heart rate every 30 min during the day (6.00 a.m. to 10 p.m.) and every 60 min during the night (10 p.m. to 6 a.m.).
Medication regimen and daily defined doses
Prescribed antihypertensive and cardiovascular medications were catalogued at each follow-up. Antihypertensive drug use over time was repeatedly assessed by the number of defined daily doses (DDD). The total number of DDDs per patient was expressed as the sum of the DDDs of each individual prescribed antihypertensive drug [9].
Endpoints
The primary efficacy endpoints were office, HBP assessed at multiple points during follow-up, cardiovascular outcomes (defined as acute coronary syndrome, hospitalization for new onset heart failure, atrial fibrillation, hypertensive crisis, stroke, and vascular complications) as well as all-cause mortality. Secondary efficacy endpoints included ABPM change, the use of antihypertensive drugs, and office heart rate throughout follow-up. The primary safety end points were change in renal function and renal-artery stenosis.
Statistical analysis
All statistical analyses were completed in GraphPad Prism (version 9.4.1; GraphPad Software, California, USA) and SPSS20.0 software. Categorical variables are reported as counts and percentages and continuous variables are reported as mean ± SD. The mean values of baseline and long-term follow-up were compared using statistical methods such as ANOVA, one-way repeated measures ANOVA, or Wilcoxon rank-sum test. Categorical variables were presented as counts and percentages and were compared between groups using the Fisher exact test for binary variables and chi-square test for multilevel categorical variables.
RESULTS
As of 1 June 2023, out of 98 eligible patients, 60 patients were available for follow-up, 37 patients were lost to follow-up, 1 patient was diagnosed with primary hyperaldosteronism 8 years after RDN (Fig. 1).
FIGURE 1.
A flowchart of participant follow-up. ABPM, ambulatory blood pressure monitoring; Cr, creatinine; HBP, home blood pressure; HR, heart rate; OBP, office blood pressure.
Baseline characteristics
Baseline characteristics of the cohort included age of 50.37 ± 15.19 years, 43.33% were women, 40% had a history of coronary artery disease, 31.67% had type 2 diabetes, 28.3% had chronic kidney disease (eGFR <60 ml/min/1.73 m2), and 11.67% had a history of atrial fibrillation. Mean baseline OSBP was 179.08 ± 22.05 mmHg and mean ODBP was 101.17 ± 16.57 mmHg. At baseline, patients were prescribed on average 3.65 ± 1.10 antihypertensive medications. Median atherosclerotic cardiovascular disease risk score at baseline was 23.6% (interquartile range: 15–32.3%) (Table 1).
TABLE 1.
Patient characteristics, co-morbid, blood pressure measurement, and number of antihypertensive drugs at baseline
| Variables | N = 60 |
| Age (years) | 50.37 ± 15.19 |
| Female | 26 (43.33%) |
| BMI (kg/m2) | 26.03 ± 3.3 |
| eGFR (ml/min/1.73 m2) | 78.36 ± 33.97 |
| Defined daily dose (DDD) at screening (mean ± SD) | 4.22 ± 1.09 |
| Number of antihypertensive medications | 3.65 ± 1.10 |
| Office SBP at baseline (mmHg) | 179.08 ± 22.05 |
| Office DBP at baseline (mmHg) | 101.17 ± 16.57 |
| Home SBP (mmHg) | 170.67 ± 15.56 |
| Home DBP (mmHg) | 95.87 ± 12.66 |
| Heart rate at baseline (bpm) | 79.2 ± 13.89 |
| History of CAD | 24 (40%) |
| History of cerebrovascular disease | 20 (33%) |
| chronic kidney disease (eGFR <60 ml/min/1.73 m2) | 17 (28.3%) |
| History of atrial fibrillation | 2 (3.33%) |
| Type 2 diabetes mellitus | 19 (31.67%) |
| History of obstructive sleep apnea | 9 (15%) |
| Smoking status | 33 (55%) |
| Median atherosclerotic cardiovascular disease risk | 23.6% (15%, 32.3%) |
Data are presented as number and percentage, mean ± SD or median (IQR). BP, blood pressure; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate.
Blood pressure changes at long-term follow-up
At baseline, average OSBP and ODBP were 179.08 ± 22.05 and 101.17 ± 16.57 mmHg, respectively, one-way ANOVA showed that OSBP (F = 183.80, P < 0.001) and ODBP (F = 67.391, P < 0.001) before and after RDN were statistically significant, Bonferroni multiple means comparison showed that the OSBP (P < 0.001) and ODBP (P < 0.001) after RDN were significantly lower than that baseline. At 1-year follow-up, OSBP and ODBP decrease by −20.72 ± 14.95 (P < 0.001) and −8.93 ± 6.92 mmHg (P < 0.001), at 5 year follow-up, OSBP and ODBP decrease by −32.34 ±−17.2 (P < 0.001) and −13.93 ± 11.57 mmHg (P < 0.001), at 10-year follow-up, OSBP and ODBP decrease by −35.93 ± 19.85 (P < 0.001) and −14.76 ± 11.85 mmHg (P < 0.001), respectively (Fig. 2 and Fig S1).
FIGURE 2.
Changes in office SBP and DBP from baseline to 1, 5, and 10 years after renal denervation. Compared with baseline, ∗∗∗P < 0.001.
After 1 and 10 years, the mean systolic 24-h ABPM values were reduced by 9.45 ± 7mmHg (P < 0.001) and 14.31 ± 10.18 (from 150.1 ± 10.27 to 134.5 ± 8.25, P < 0.001), respectively, when compared with baseline (P < 0.001). Corresponding diastolic values were reduced by 5.14 ± 2.67 and 9 ± 4.35 mmHg (from 92.15 ± 7.43 to 82.94 ± 5.08, P < 0.001; (Fig. 3).
FIGURE 3.
Change in ambulatory SBP and DBP from baseline to 1 and 10 years after renal denervation. Compared with baseline, ∗∗∗P < 0.001.
The home SBP (HSBP) and home DBP (HDBP) was 170.67 ± 15.56 and 95.87 ± 12.66 at baseline. One-way ANOVA showed that there were significant differences in home SBP (F = 146.97, P < 0.001) and DBP (F = 52.8, P < 0.001) before and after RDN, Greenhouse–Geisser results showed that the HSBP (P < 0.005) and HDBP (P < 0.001) after RDN were significantly lower than that baseline, However, there was no significant difference in home SBP between 5 and 10 years after RDN. At 5 year follow-up, HSBP and HDBP decrease by −24.60 ± 13.56 (P < 0.001) and −10.12 ± 15.3 mmHg (P < 0.001), at 10-year follow-up, HSBP and HDBP decrease by 26.76 ± 14.47 (P < 0.001) and 10.17 ± 10. 7 mmHg (P < 0.001), respectively (Fig. S2).
Heart rate changes at long-term follow up
Heart rate is recognized as an indicator of sympathetic excitability. Mean heart rates at baseline and 10 years after RDN were collected for this study. Heart rate decreased from 79.12 ± 14.13 at baseline to 73.29 ± 8.72 bpm at 10 years after RDN (P < 0.001) Fig. S3.
Changes in medication use
The number of DDD significantly decreased (P < 0.05), from 4.22 ± 1.09 at baseline to 2.86 ± 0.78 10 years after RDN, Fig. S4. By analyzing the drug composition after 10 years of RDN. we found that the proportion of spironolactone was slightly higher (χ2 = 2.95, P = 0.086) and the proportion of β receptor inhibitor significantly decreased (χ2 = 25.59, P < 0.001).
Effect of renal denervation on renal function
In terms of safety, we followed creatinine and eGFR at 1 and 10 years after RDN. There were no significant changes in creatinine level at 1 and 10 years after RDN. There was no significant decrease in eGFR at 1 year after RDN, but there was a significant decrease in eGFR at 10 years after RDN (Fig. 4). It is considered that this may be related to the increasing age of the patient.
FIGURE 4.
Changes in renal function from baseline to 1 and 10 years after renal denervation. Compared with baseline, ∗P < 0.05.
Indications for renal denervation in the treatment of hypertension
In order to explore, which patients are more suitable for RDN treatment, all patients in this study were divided into high renin group and low renin group according to the median renin level. The results showed that the SBP decreased more in the high renin group than in the low renin group, while there was no statistically significant difference in DBP between the two groups, after 10 years follow-up, as shown Fig. 5a. We then divided all patients into a higher SBP group and a lower SBP group according to the baseline median office SBP level, we found that the higher baseline SBP group had a more significant reduction of office SBP after 10 years follow-up. In addition, office DBP was also significantly lower in the higher baseline SBP group than in the lower baseline SBP group at 10 years after RDN (Fig. 5b). We also divided all the patients into a higher heart rate group and a lower heart rate group according to the median baseline heart rate. By analyzing the data, we were surprised to find that there was no statistically significant difference in SBP and DBP between the higher and lower baseline heart rate groups 10 years after RDN (Fig. 5c).
FIGURE 5.
Changes in blood pressure in different subgroups according to renin levels (a), baseline SBP (b), and heart rate (c). Compared with baseline, ∗P < 0.05, ∗∗∗P < 0.001.
Major adverse events at follow-up
In our long-term follow-up of 60 patients, nonfatal major adverse events were occurred in 11 patients, including four nonfatal strokes, two nonfatal myocardial infarction, two percutaneous coronary intervention (PCI)for unstable angina, and three acute heart failure. One patient received peritoneal dialysis due to renal failure. Another patient developed renal artery stenosis 9 years after RDN, which was considered to be unrelated to RDN. Ten-year all-cause mortality was 10% after RDN, and the 10 years cardiovascular mortality was 8.34%. Of those who died because of cardiovascular causes during the follow-up period, two died from acute heart failure, one died from acute myocardial infarction, and two because of stroke. The other patient died of noncardiovascular causes, he died of lung malignancy tumor (Fig. S5).
DISCUSSION
This study was conducted as a single-arm single-center trial, lacking a control group. The findings of this study provide valuable insights into the efficacy of RDN in real-world patients over a period of more than 10 years, allowing for a more accurate assessment of its true effects. After a follow-up period of 10 years, a statistically and clinically significant reduction in OBP was observed, despite a decrease in the use of antihypertensive medications. Additionally, RDN led to a significant decrease in HBP and ABPM. Furthermore, the long-term safety of RDN was maintained, as no adverse effects were reported.
After a decade following RDN, a total of six patients (10%) succumbed, with two fatalities attributed to a verified stroke, two to acute heart failure, one to acute myocardial infarction and one to lung cancer. Regarding safety indicators, there was no statistically significant alteration in creatinine levels 10 years post-RDN; however, there was a slight decline in eGFR. Furthermore, one patient experienced the emergence of new renal artery stenosis 9 years after RDN, although this occurrence was unrelated to the RDN procedure.
This study, similar to several recently published studies [9–12], provides further evidence that the BP-lowering effects of RDN are long-lasting, lasting up to 10 years and potentially increasing over time. In our study, we observed a significant decrease in BP of −35.93/−14.76 mmHg at 10 years after RDN. Previous research has suggested that Asian populations may exhibit a more favorable response to RDN for sympathetic mediated hypertension compared with other ethnic groups. In a subgroup analysis of GSR patients in Taiwan, those who underwent renal denervation experienced an average reduction in office SBP of −29.7 ± 25.9 mmHg after 3 years of follow-up [13]. Similarly, the SYMPLICITY HTN-Japan study also reported significant BP reductions in patients treated with renal denervation [14].
Renal denervation led to mean (± standard deviation) reductions in office SBP at 12, 24 and 36 months in GSR Korea (−26.7 ± 18.5, −30.1 ± 21.6 mmHg, and −32.5 ± 18.8, respectively) [15]. In addition to office BP monitoring, HBP monitoring was also followed. The HBP monitoring method can provide a better picture of the BP status of hypertensive patients as it can eliminate white-coat hypertension caused by office BP measurement as well as pseudohypertension caused by frequent BP measurements in 24-h ABPM. In addition, although only 27% of the patients in this study completed 24-h ABPM, from the patients who completed 24-h ABPM, the mean ambulatory SBP and DBP decreased significantly 10 years after RDN.
It is important to emphasize that the decrease in BP was not due to an increase in medication. However, the study did find an increase in the use of spironolactone after RDN, although it was not statistically significant. Previous studies have shown that spironolactone increases the rate of BP control in patients with resistant hypertension. Recent evidence suggests that spironolactone was the most effective add-on drug for the treatment of resistant hypertension [16]. Aldosterone antagonist such as spironolactone has been recognized as the preferred add-on therapy for BP-lowering in resistant hypertension since the publication of the PATHYWAY-2 clinical trial. A recent study also showed the greatest BP reductions with amlodipine and olmesartan after RDN [17]. In our study, we found a reduction in β-blocker use after RDN. Therefore, the reduced antihypertensive load may be related to the decrease in the use of β receptor inhibitors.
However, in our study, approximately 30% of patients failed to benefit from this procedure in terms of a significant reduction in BP. It is possible to achieve a significant and lasting reduction in BP by reducing sympathetic activity in 60–70% of cases. Moreover, there are no reliable clinical or biochemical factors that can be used to predict efficacy. The BP response to RDN is inherently heterogeneous and difficult to predict. RDN success appears to be determined by the baseline levels of renin, with higher renin levels associated with greater reductions in BP, as in the cohorts with long-term follow-up. Identifying likely responders in advance may improve the cost-effectiveness of the procedure. RDN has been demonstrated in previous research to reduce renin levels [17–19], and our team's studies indicate that hypertensive patients with high renin levels have better treatment outcomes when taking RDN [20]. As a result of this 10-year follow-up study, it has also been confirmed that RDN is more effective at lowering BP in hypertensive patients with a high renin level, providing strong evidence for the selection of RDN indications in the future. Furthermore, we observed that people with a higher baseline SBP experienced a greater reduction in BP. In spite of the fact that heart rate can be regarded as an important measure of sympathetic excitability, people with higher heart rates did not experience a greater reduction in BP.
RDN also exhibits an increased BP-lowering effect over time. It was interesting to note that the antihypertensive effect of RDN decreased with time from the initial negative results of the Symplicity HTN-3 study to the significant decrease in BP at the 3-year follow-up, and even to the 10-year follow-up of the present study [1], This made us wonder what was happening. Renal sympathetic remodeling and even systemic sympathetic nerve remodeling (sympathetic rebalancing) occur over time after RDN, unlike the central nerves, the sympathetic nerves in the postganglionic kidney are not myelinated. Lack of myelin causes no clear structural framework for nerve regeneration after ablation. Histological analysis of renal tissue after radiofrequency denervation in a normotensive porcine model revealed transient nerve necrosis after RDN, followed by persistent fibrosis of the renal nerve at the ablation site. Further investigation revealed a sustained reduction in renal NE, cortical axonal density, and downstream axonal loss caused by axonal breakdown at 180 days after RDN. These findings were associated with downstream axonal destruction and atrophic nerve body changes, suggesting irreparable damage to neural structures infiltrated by mature fibers at 180 days. The results of this study suggest that functional nerve regeneration is unlikely after RF RDN and support published clinical evidence that the procedure results in long-lasting BP reduction [21].
In contrast to other studies, this study monitored patients for 10 years after RDN for hard endpoints such as adverse cardiovascular events and death from cardiovascular disease. There is evidence that patients with the highest baseline ASCVD risk scores (20%) have a higher 3-year death rate (8.4%) and a higher cardiovascular death rate (4.5%) [22]. In this study, however, the median ASCVD score was 23.6%, indicating that the majority of patients were at high risk. Following a 10-year follow-up period, the incidence of all-cause mortality was 10% and cardiovascular mortality was 8.34%, suggesting that RDN may reduce mortality related to cardiovascular or all-cause disease. An explanation for this might have to do with the timing of treatment range after RDN, as one study demonstrated sustained reductions in BP and higher time in therapeutic range (TTR) through 36 months after RDN. A 10% increase in TTR through 6 months was associated with a substantial reduction in major cardiovascular events [23]. The results of the recent STEP study showed that BP control below 130 mmHg was beneficial in elderly hypertensive patients in China; therefore, strict BP control seems to be very important for prevention of cardiovascular events in Asia [24].
It is also important to emphasize the safety of RDN, as renal function (creatinine) remained stable despite a slight increase in eGFR, taking into account factors associated with aging. Aside from this, the study only found one case of renal artery stenosis, which occurred 9 years after RDN and did not appear to be related to RDN.
In summary, the characteristics of this study are as follows: the long follow-up period; the risk of major adverse cardiovascular events and cardiovascular mortality at 10 years after RDN in the real world is evaluated; the majority of the patients enrolled were at high cardiovascular risk at baseline; the reduction of antihypertensive drugs after RDN is primarily attributed to β-blockers; patients with high renin levels may benefit more from RDN's antihypertensive effects.
Study limitations
There are some limitations in our study. Firstly, based on the nature of this real-world study, there is no control group for comparison. Additionally, medication adherence was not assessed with blood or urine tests because this goes beyond the scope of this real-world study. Antihypertensive medications were documented with prescriptions. Moreover, not all patients reached a 10-year follow-up at the time of this report, and patients who completed ABP measurements were in the minority. Lastly, we did not account for changes in lifestyle, such as food and salt intake, which might have contributed to BP changes.
In conclusion, in this real-world study of patients with resistant hypertension, RDN safely and consistently lowered BP with reduced BP-lowering medication use through 10 years. RDN treatment may be more appropriate in hypertensive patients with high renin levels or high baseline SBP. As well, to my knowledge, this is the first study that indicates that RDN may reduce 10-year mortality from all causes and cardiovascular diseases.
ACKNOWLEDGEMENTS
We thank all the researchers who participated in this work.
Funding: this work was supported by the Scientific and Technological Personnel Training Project of Tianjin Health and Family Planning Commission (KJ20007), Science and Technology Fund of Tianjin First Central Hospital (No. 2020CM11), National Natural Science Foundation of China (Grant No. 81970303), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-054B) and the Natural Science Foundation of Tianjin (21JCYBJC00250).
Authors’ contributions: L.W. contributed to writing the manuscript, L.W., Z.Q.L. and Q.L. contributed to the data analysis. C.Z.L., C.L., Q.H., D.S.X. and D.C.X. participate in RDN treatment, Z.Q.L., Q.L., C.L.L., and X.Q.S. contributed to the revision of the manuscript. L.W. and C.Z.L. contributed to the conception and design of the project.
Ethics approval and consent to participate; not applicable.
Availability of data and materials: the data will be made available by the corresponding author upon request.
Conflicts of interest
There are no conflicts of interest.
Supplementary Material
Supplementary Material
Supplementary Material
Supplementary Material
Supplementary Material
Footnotes
Abbreviations: BP, blood pressure; CAD, coronary artery disease; DDD, defined daily doses; eGFR, estimated glomerular filtration rate; HBP, home blood pressure; HDBP, home DBP; HSBP, home SBP; MACE, major adverse cardiovascular events; MI, myocardial infarction; OBP, office blood pressure; ODBP, office DBP; OSBP, office SBP; RDN, renal denervation
Supplemental digital content is available for this article.
REFERENCES
- 1.Bhatt DL, Vaduganathan M, Kandzari DE, Leon MB, Rocha-Singh K, Townsend RR, et al. SYMPLICITY HTN-3 Steering Committee Investigators. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet 2022; 400:1405–1416. [DOI] [PubMed] [Google Scholar]
- 2.Azizi M, Saxena M, Wang Y, Jenkins JS, Devireddy C, Rader F, et al. RADIANCE II Investigators and Collaborators. Endovascular ultrasound renal denervation to treat hypertension: the RADIANCE II Randomized Clinical Trial. JAMA 2023; 329:651–661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Worthley SG, Tsioufis CP, Worthley MI, Sinhal A, Chew DP, Meredith IT, et al. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J 2013; 34:2132–2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mahfoud F, Kandzari DE, Kario K, Townsend RR, Weber MA, Schmieder RE, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet 2022; 399:1401–1410. [DOI] [PubMed] [Google Scholar]
- 5.Roubsanthisuk W, Kunanon S, Chattranukulchai P, Panchavinnin P, Wongpraparut N, Chaipromprasit J, et al. 2022 Renal denervation therapy for the treatment of hypertension: a statement from the Thai Hypertension Society. Hypertens Res 2023; 46:898–912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chia YC, Wan Ahmad WA, Fong AYY, Rosman A, Abdul Rahman AR, Choo GH, et al. 2022 Malaysian Working Group Consensus Statement on Renal Denervation for management of arterial hypertension. Hypertens Res 2022; 45:1111–1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Barbato E, Azizi M, Schmieder RE, Lauder L, Böhm M, Brouwers S, et al. Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2023; 44:1313–1330. [DOI] [PubMed] [Google Scholar]
- 8.Jones DW, Hall JE. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and evidence from new hypertension trials. Hypertension 2004; 43:1–3. [DOI] [PubMed] [Google Scholar]
- 9.Zeijen VJM, Feyz L, Nannan Panday R, Veen K, Versmissen J, Kardys I, et al. Long-term follow-up of patients undergoing renal sympathetic denervation. Clin Res Cardiol 2022; 111:1256–1268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Mahfoud F, Townsend RR, Kandzari DE, Kario K, Schmieder RE, Tsioufis K, et al. Changes in plasma renin activity after renal artery sympathetic denervation. J Am Coll Cardiol 2021; 77:2909–2919. [DOI] [PubMed] [Google Scholar]
- 11.Wang L, Lu CZ, Zhang X, Zhang F, Xia DS, Chen X, et al. Effect of catheter based radiofrequency ablation on resistant hypertension patients with high renin levels. Zhong hua gao xue ya za zhi 2014; 22:1084–1086. [Google Scholar]
- 12.Sesa-Ashton G, Nolde JM, Muente I, Carnagarin R, Lee R, Macefield VG, et al. Catheter-based renal denervation: 9-year follow-up data on safety and blood pressure reduction in patients with resistant hypertension. Hypertension 2023; 80:811–819. [DOI] [PubMed] [Google Scholar]
- 13.Al Ghorani H, Kulenthiran S, Recktenwald MJM, Lauder L, Kunz M, Götzinger F, et al. 10-year outcomes of catheter-based renal denervation in patients with resistant hypertension. J Am Coll Cardiol 2023; 81:517–519. [DOI] [PubMed] [Google Scholar]
- 14.Panchavinnin P, Wanthong S, Roubsanthisuk W, Tresukosol D, Buranakitjaroen P, Chotruangnapa C, et al. Long-term outcome of renal nerve denervation (RDN) for resistant hypertension. Hypertens Res 2022; 45:962–966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lee CK, Wang TD, Lee YH, Fahy M, Lee CH, Sung SH, et al. Efficacy and safety of renal denervation for patients with uncontrolled hypertension in Taiwan: 3-year results from the Global SYMPLICITY Registry-Taiwan (GSR-Taiwan). Acta Cardiol Sin 2019; 35:618–626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Kario K, Yamamoto E, Tomita H, Okura T, Saito S, Ueno T, et al. Sufficient and persistent blood pressure reduction in the final long-term results from SYMPLICITY HTN-Japan- Safety and Efficacy of Renal Denervation at 3 Years. Circ J 2019; 83:622–629. [DOI] [PubMed] [Google Scholar]
- 17.Kim BK, Kim HS, Park SJ, Park CG, Seung KB, Gwon HC, et al. Long-term outcomes after renal denervation in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea). Hypertens Res 2021; 44:1099–1104. [DOI] [PubMed] [Google Scholar]
- 18.Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386:2059–2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Hohl M, Lauder L, Sevimli Ö, Tokcan M, Wagmann L, Götzinger F, et al. Efficacy of antihypertensive drugs of different classes after renal denervation in spontaneously hypertensive rats. Hypertension 2023; 80:e90–e100. [DOI] [PubMed] [Google Scholar]
- 20.Yang X, Lin L, Zhang Z, Chen X. Effects of catheter-based renal denervation on renin-aldosterone system, catecholamines, and electrolytes: a systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2022; 24:1537–1546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Sharp ASP, Tunev S, Schlaich M, Lee DP, Finn AV, Trudel J, et al. Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model. J Hypertens 2022; 40:2068–2075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, Ruilope L, Schlaich M, et al. Renal denervation in high-risk patients with hypertension. J Am Coll Cardiol 2020; 75:2879–2888. [DOI] [PubMed] [Google Scholar]
- 23.Mahfoud F, Mancia G, Schmieder RE, Ruilope L, Narkiewicz K, Schlaich M, et al. Cardiovascular risk reduction after renal denervation according to time in therapeutic systolic blood pressure range. J Am Coll Cardiol 2022; 80:1871–1880. [DOI] [PubMed] [Google Scholar]
- 24.Zhang W, Zhang S, Deng Y, Wu S, Ren J, Sun G, et al. Trial of intensive blood-pressure control in older patients with hypertension. N Engl J Med 2021; 385:1268–1279. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.