Abstract
Background
The endovascular approach of ablation of renal sympathetic nerves is found to be effective in the treatment of uncontrolled hypertension. We report here our experience with the procedure in eight patients with drug resistant hypertension.
Methods
We included patients in whom the blood pressure remained above 150/90 mmHg despite being on minimum three antihypertensive drugs. Radiofrequency ablation of the sympathetic nerves of both the renal arteries was done using conventional ablation catheters. The patients were followed at 1-month, 3 months and 6 months post procedure and blood pressure recorded.
Results
All patients underwent successful renal sympathetic denervation. The mean blood pressure of the patients was 181/102.5 mmHg before the procedure and the average requirement of antihypertensive drugs per day was 4. A significant reduction in both systolic and diastolic blood pressure was observed post procedure which sustained over the follow up period of six months. The mean blood pressure observed at 1-month, 3 and 6 months were 137.5/80 mmHg, 136/81 mmHg and 137.5/81 mmHg, respectively. The average requirement of the number of antihypertensives also was reduced to 2.5 at the end of 6 months. There were no procedural complications.
Conclusion
Catheter based renal denervation causes substantial and sustained blood pressure reduction without serious adverse events in patients with resistant hypertension.
Keywords: Resistant hypertension, Renal sympathetic denervation, Radiofrequency ablation
1. Introduction
Despite the availability of an array of potent pharmacological agents for the treatment of hypertension, resistant hypertension (RH) continues to be a therapeutic challenge for physicians. RH is defined as “blood pressure (BP) that remains uncontrolled despite the concurrent use of 3 or more antihypertensive agents of different classes including a diuretic prescribed in optimal doses”.1 Blood pressure that gets controlled with the use of four or more medications is also categorized as RH. The prevalence of true RH is estimated to be around 5%.2,3 These patients carry a two to three fold risk of developing hypertension related cardiovascular complications compared to those hypertensives in whom BP is easily manageable.4–6 Apart from drug intolerance, patient non-compliance and non-adherence to lifelong drug therapy and other lifestyle modifications are additional challenges in the treatment of RH. Recently, catheter based ablation of renal sympathetic nerves has emerged as a novel therapeutic option for this sub-set of patients.
Renal sympathetic denervation (RDN), by targeting the renal nerves, cuts the crucial link between sympathetic nervous system activation and hypertension. This endovascular approach using a dedicated catheter (Simplicity) has been proven to be safe and efficacious in clinical studies including a randomized trial.7–11 In this procedure, a catheter connected to a radiofrequency (RF) generator is used to cause sympathetic denervation which is achieved percutaneously through the lumen of the main renal artery. We report here our experience with this procedure using conventional radiofrequency ablation catheters in eight patients with RH.
2. Methods
The study was done with the approval of the institutional ethics committee. Consecutive 18 patients from August 2011 till June 2012 with RH who consented for the RDN procedure were screened for eligibility. Patients whose average BP recording was 150/90 or more (on at least 3 antihypertensives) on 24 h BP monitoring were considered for the study. Further eligibility was confirmed after renal angiogram. Patients who were found to have renal artery stenosis or unsuitable renal anatomy for the procedure were excluded from the study. Patients who had deranged renal parameters but not on renal dialysis, those who had valvular heart disease, female patients who were pregnant or were planning for pregnancy, patients with history of renal artery intervention and those with history of coronary syndrome or cerebrovascular accident within the preceding six months were also excluded.
Renal angiogram was done using the right femoral approach and in those who had suitable renal artery, RDN was done using radiofrequency catheter ablation.
2.1. Renal denervation procedure
A 6F deflectable CELSIUS Thermistor (Biosense Webster, Diamond Bar, CA, USA) conventional RF ablation catheter was advanced into the renal arteries through Mullins sheath. A Stockert RF generator was used to deliver RF energy in unipolar mode. We delivered RF energy for 60–90 s each and of 8–12 W and created 5–6 focal lesions, longitudinally separated along the length of each renal artery. The cut off point was taken as a reduction in impedance by 10%. The catheter tip impedance was monitored continuously. RF delivery was stopped if there was rise in impedance by more than 5 Ω.
Post procedure renal angiogram was done to assess for procedural complications within the renal arteries. Patients were discharged on second post procedure day. A complete physical examination including 24 h ambulatory BP monitoring, drug compliance and renal profile which were assessed at baseline were repeated at one, three and six months post RDN.
3. Results
Of the 18 patients screened, eight qualified the inclusion and exclusion criteria. The BP was uncontrolled (mean 181/102 mmHg) in all the patients despite being on maximum tolerated doses of antihypertensive drugs for more than six months. Baseline characteristics and clinical profile of the patients are given in Table 1.
Table 1.
Baseline characteristics and co-morbidities.
| S. no. | Age in years/Sex | Pre-procedure drugs and dosages | Mean blood pressure (mmHg) | S. creatinine (mg/dl) | Duration of optimum treatment before procedure | Post procedure drugs and dosages |
|---|---|---|---|---|---|---|
| 1 | 35/M | Amlodipine 10 mg bid, Metoprolol XR 100 mg od, Hydrochlorothiazide 25 mg od | 170/100 | 1.0 | 9 months | Amlodipine 5 mg od, Hydrochlorothiazide 25 mg od |
| 2 | 24/F | Prazosin 10 mg od, Metoprolol 50 mg od, Furosemide 40 mg bid, Clonidine 100 mcg tid, Telmisartan 80 mg od | 240/130 | 7.1 | 4 years | Prazosin 10 mg od, Metoprolol 50 mg od, Clonidine 100 mcg tid |
| 3 | 62/M | Prazosin 10 mg od, Carvedilol 25 mg od, Hydrochlorothiazide 25 mg od, Clonidine 100 mcg tid, Telmisartan 80 mg od | 170/100 | 0.9 | 3 years | Carvedilol 25 mg, Telmisartan 40 mg od |
| 4 | 62/F | Ramipril 10 mg od, Metoprolol 100 mg od, Hydrochlorothiazide 25 mg od, Amlodipine 10 mg od | 170/100 | 0.9 | 6 years | Ramipril 5 mg od, Metoprolol 50 mg od |
| 5 | 57/M | Carvedilol 25 mg od, Amlodipine 10 mg od, Telmisartan 80 mg od, Prazosin 10 mg od, Clonidine 100 mcg tid, Hydrochlorothiazide 25 mg od | 180/100 | 1.1 | 4 years | Carvedilol 12.5 mg od, Telmisartan 40 mg od |
| 6 | 53/F | Metoprolol 100 mg od, Amlodipine 10 mg od, Losartan 25 mg bd, Prazosin 10 mg od, Clonidine 100 mcg tid, Furosemide 40 mg bid | 170/100 | 5.0 | 2 years | Metoprolol 100 mg od, Amlodipine 10 mg od, Clonidine 100 mcg tid |
| 7 | 53/M | Ramipril 10 mg od, Metoprolol 50 mg od, Hydrochlorothiazide 25 mg od, Amlodipine 10 mg od | 180/100 | 2.5 | 3 years | Ramipril 10 mg od, Metoprolol 50 mg od |
| 8 | 55/M | Prazosin 10 mg od, Carvedilol 25 mg od, Hydrochlorothiazide 25 mg od, Clonidine 100 mcg tid, Ramipril 10 mg od | 170/90 | 1.0 | 3 years | Cardivas 25 mg, Ramipril 10 mg od |
All patients underwent the RDN procedure successfully. Within 48–72 h following the procedure, we observed a significant drop in BP (mean 130/80 mmHg) which stabilized later. The duration of the procedure averaged 40 min. This reduction of BP was observed in all the eight patients and sustained over follow up period (Figs. 1 and 2). At the end of six months post RDN, we observed a reduction of 24% of systolic and 20.7% of diastolic BP.
Fig. 1.
Change in systolic BP from baseline to six months post RDN.
Fig. 2.
Change in diastolic BP from baseline to six months post RDN.
There were no procedure related complications. Renal functions were unaffected as evidenced by the unaltered renal parameters post procedure.
4. Discussion
It is known that sympathetic nervous system (SNS) plays a vital role in the initiation and maintenance of high blood pressure (11). The degree of SNS activation correlates with the severity of hypertension. Overdrive of SNS has also been found to be associated with target-organ damage associated with chronic hypertension.12 Before the advent of pharmacological agents, surgical approaches were used to directly target the SNS for hypertension control using procedures like splanchnicectomy and radical sympathectomy. Though efficient in BP reduction, the safety aspect was severely compromised in these procedures as the renal arteries were not selectively targeted. The response of kidney to SNS signaling is considered as one important mechanism which raises BP. The renal sympathetic stimulation increases renin secretion, reduces urinary sodium excretion and induces vasoconstriction.12,13 Therefore, by specifically targeting the renal efferent sympathetic and sensory afferent signaling, it was considered possible to achieve BP reductions with reasonable safety which was not possible with the earlier surgical approaches. The renal sympathetic nerves arise from T10-L1 and enter the kidneys through the renal arteries and lie within the adventitia, within easy reach for the delivery of radiofrequency energy delivery. This relatively easy and selective approachability of the renal nerves has brought renal denervation back to focus.
In line with the previously conducted studies,7–11 we found that the catheter based RDN procedure using RF energy to be a very effective and safe procedure. The RDN procedure achieved a significant reduction in both systolic and diastolic BP. The mean reduction of office BP at the end of six months was −43.5/−21 mmHg. The average number of antihypertensive drugs was also reduced from four pre-procedure to two at the end of six months post RDN. The procedure also had an excellent short and intermediate safety profile. Renal angiogram immediately following the procedure did not show any injury to the renal arteries. The procedure was found to be effective in patients with chronic renal dysfunction also. These patients continued to be on dialysis even after RDN but their requirement of antihypertensive drugs was reduced. Blood renal profile at the end of six months also remained stable indicating normally functioning kidneys.
5. Limitations
Our study is proof of concept study demonstrating the efficacy and safety of conventional radiofrequency ablation catheter for renal denervation. This study revealed that renal denervation performed with the conventional radiofrequency ablation catheter is effective and is likely to be less expensive. In our study, we have not monitored the GFR in chronic kidney disease patients. The effect of renal denervation on renal function in chronic kidney disease patients needs to be evaluated in randomized control trials. It should be emphasized that medical therapy and lifestyle modifications should be continued in these patients in spite of RDN therapy. However, large randomized controlled studies using this technique will be needed to prove the efficacy of this therapy.
Conflicts of interest
All authors have none to declare.
References
- 1.Calhoun D.A., Jones D., Textor S. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–e526. doi: 10.1161/CIRCULATIONAHA.108.189141. [DOI] [PubMed] [Google Scholar]
- 2.Sarafidis P.A., Bakris G.L. Resistant hypertension. An overview of evaluation and treatment. J Am Coll Cardiol. 2008;52:1749–1757. doi: 10.1016/j.jacc.2008.08.036. [DOI] [PubMed] [Google Scholar]
- 3.Moserand M., Setaro J.F. Resistant or difficult-to-control hypertension. N Engl J Med. 2006;355:385–392. doi: 10.1056/NEJMcp041698. [DOI] [PubMed] [Google Scholar]
- 4.Isaksson H., Ostergren J. Prognosis in therapy-resistant hypertension. J Intern Med. 1994;236:643–649. doi: 10.1111/j.1365-2796.1994.tb00857.x. [DOI] [PubMed] [Google Scholar]
- 5.Pierdomenico S.D., Lapenna D., Bucci A. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens. 2005;18:1422–1428. doi: 10.1016/j.amjhyper.2005.05.014. [DOI] [PubMed] [Google Scholar]
- 6.Benetos A., Thomas F., Bean K., Gautier S., Smulyan H., Guize L. Prognostic value of systolic and diastolic blood pressure in treated hypertensive men. Arc Intern Med. 2002;162:577–581. doi: 10.1001/archinte.162.5.577. [DOI] [PubMed] [Google Scholar]
- 7.Krum H., Schlaich M., Whitbourn R. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–1281. doi: 10.1016/S0140-6736(09)60566-3. [DOI] [PubMed] [Google Scholar]
- 8.Schlaich M.P., Sobotka P.A., Krum H., Lambert E., Esler M.D. Renal sympathetic–nerve ablation for uncontrolled hypertension. N Eng J Med. 2009;361:932–934. doi: 10.1056/NEJMc0904179. [DOI] [PubMed] [Google Scholar]
- 9.Prochnau D., Lucas N., Kuehnert H., Figulla H.R., Surber R. Catheter-based renal denervation for drug-resistant hypertension by using a standard electrophysiology catheter. EuroIntervention. Jan 2012;7:1077–1080. doi: 10.4244/EIJV7I9A171. [DOI] [PubMed] [Google Scholar]
- 10.Symplicity HTN-1 Investigators Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:911–917. doi: 10.1161/HYPERTENSIONAHA.110.163014. [DOI] [PubMed] [Google Scholar]
- 11.Symplicity HTN-2 Investigators Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomized, controlled trial. The Lancet. 2010;376:1093–1909. doi: 10.1016/S0140-6736(10)62039-9. [DOI] [PubMed] [Google Scholar]
- 12.Grassi G. Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives. Hypertension. 2009;54:690–697. doi: 10.1161/HYPERTENSIONAHA.108.119883. [DOI] [PubMed] [Google Scholar]
- 13.Schlaich M.P., Sobotka P.A., Krum H., Whitbourn R., Walton A., Esler M.D. Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. Hypertension. 2009;54:1195–1201. doi: 10.1161/HYPERTENSIONAHA.109.138610. [DOI] [PubMed] [Google Scholar]