Hypertension is a public health problem of the first magnitude because of its high prevalence and the significant increase in cardiovascular morbidity and mortality involved.1 Currently, the treatment of hypertension is based on 2 factors: modifying certain lifestyle habits and the use of antihypertensive drugs.2 Blood pressure (BP) control continues to be poor in almost 50% of hypertensive patients3,4 due to poor adherence to treatment and/or the inefficacy of the available drugs.

In this setting, resistant hypertension (RH) is defined as a situation in which the BP values are >140/90 mmHg despite the patient taking 3 or more drugs, including a diuretic, at appropriate doses.5 The prevalence of RH remains unclear, but it is estimated at around 13% of the patients in treatment. The presence of RH entails an increase in mortality and increased disease in target organs compared to the rest of the hypertensive population.6

The sympathetic nervous system plays an important role in the persistence and progression of hypertension. Sympathetic innervation reaches the kidney through the adventitia of the renal artery. Efferent sympathetic nerve activity produces renal vasoconstriction and increases renin production and sodium retention, leading to increased blood volume and thus increased BP; in turn, afferent renal sympathetic nerves, in response to hypoperfusion, modulate the systemic sympathetic response to produce vasoconstriction and an increase in BP.7,8

Recently, catheter-based renal denervation (RD) has been developed, a procedure based on the application of radiofrequency energy within renal arteries to modulate the mechanisms described above. After a promising preclinical study9 in animal models, the efficacy and safety of this therapy in humans was supported by the Symplicity studies. The nonrandomized Symplicity HTN-1 study10 demonstrated the feasibility and safety of RD, without ablation-associated complications in renal arteries. Subsequently, the Symplicity HTN-2 trial,11 which included 106 patients randomized to conventional treatment or RD, showed a decrease in office blood pressure measurements (OBPM) of 30/11 mmHg at 6 months, with a reduction in drug treatment in 20% of denervated patients. The longer-term follow-up of patients from the Symplicity HTN-1 study showed that the benefit of this therapy was sustained for at least 2 years of follow-up.12

Currently, little information is available on the clinical setting in which this therapy is provided, the specialists who perform it, and the results it can offer outside the context of clinical trials.

The aim of this study was to describe the creation of a multidisciplinary RD unit integrated within the hospital's nephrology and cardiology services and the implementation and outcomes of the RH management program designed for this unit.

The RD program implemented in our center obtained results that confirm the scientific evidence regarding the role of renal ablation in improving BP control, as shown by the reduction in both OBPM and ABPM values.

Candidate selection was based on the exclusion of pseudoresistent hypertension by clinical assessment, ABPM, and response to treatment with aldosterone antagonists. In this sense, it differs from the Symplicity trial, which used the systolic BP value (>160 mmHg) alone to select candidates for ablation. Observational studies have shown that aldosterone antagonists significantly improve BP control in resistant patients,13–16 bearing in mind the possible occurrence of secondary hyperaldosteronism. The only randomized trial currently available also demonstrated a favorable, although moderate, effect of spironolactone vs placebo in RH control.17 Despite this evidence, it is noteworthy that 17% of the patients included in the Symplicity trial were treated with aldosterone antagonists compared to 82% of the patients in our series, all nonresponders who were maintained on these drugs before ablation. Although it is unknown whether treatment with aldosterone antagonists can improve the response to RD, in our series the administration of aldosterone antagonists improved BP control in 60 of 89 patients (67%) with true RH, indicating that once the pseudoresistant population is excluded, therapeutic treatment with aldosterone antagonists can reduce the need for renal ablation in a large number of patients.

The decrease in OBPM values by 25/10 mmHg after 72-day follow-up is similar to that reported in the Symplicity HTN-2 trial11 (24/8 mmHg at 3 months). However, the reduction in the use of antihypertensive drugs was much greater in our series than was described in that study (91% vs 20% of patients, respectively). However, reducing the number of drugs was not formally included in the clinical trial, whereas this was an aim in our protocol, which may partly explain the difference found. The only reduction that did not reach statistical significance was diastolic OBPM; this is probably explained by white-coat syndrome having a relatively stronger effect on these values than it does on systolic BP values or ABPM pressures. The diastolic OBPM values were demonstrated as only having a tendency to decrease, which may have reached statistical significance had more patients been included in the sample.

The RD procedure is characterized by the absence of a specific target other than completing a specific number of lesions in each artery. Currently, the optimal number of applications remains unknown; both Symplicity trials10,11 administered between 4 and 6 applications. Given the uncertainty about a potential dose-response effect, the procedure designed in our center is based on the idea of creating as many lesions as possible (up to 8 per artery). Thus, the maximum number of lesions possible depends on the length of artery treated and whether or not there are anatomical variants. In this sense, preoperative rotational aortography has proved very useful, since the projection in which the artery is longest can be selected, which facilitates a greater number of applications (Fig. 4).

Figure 4.

Illustration showing how rotational angiography may be used to select the oblique projection in which the length of the artery is at its greatest. A and B, images acquired by rotational angiography in different right oblique views of the right renal artery; note how the length of the vessel is shown at its longest in B. C and D, working projections equivalent to image A and B, respectively. D, projection that allows the retraction of the catheter while performing a greater number of applications than in the projection shown in C.

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Anatomical variants or lesions were identified in 6 of 11 patients, either by CTA or, more often, during the operation itself. The presence of nonsignificant stenosis or polar arteries was not an exclusion criterion for RD, whereas this was a criterion in the Symplicity studies. In the 3 patients with polar arteries, ablation was performed in the main renal artery alone. A more conservative approach would be to perform RD in the kidney without abnormalities or anatomical variants, but it is currently unknown which of the two has the better risk-benefit ratio. The presence of bifurcations, secondary branches, or renal artery stenosis highlights the need for careful anatomical assessment of the vessel during the procedure to ensure safety.

The manufacturer recommends creating lesions in a spiral pattern along the arterial wall to achieve a higher proportion of sympathetic innervation and avoid potential complications such as vessel stenosis. Since conventional fluoroscopy is a 2-dimensional imaging technique, it cannot accurately determine the actual position of the catheter relative to the artery wall. In this sense, fluoroscopic navigation makes it easier to create the spiral pattern, since the position of the previous applications can be marked (Fig. 1). Another potential benefit is provided if a second ablation procedure is needed in a nonresponder patient, since a map of the previous applications is available.

One of the patients presented normal BP at the first follow-up visit. After presenting symptoms of orthostasis, antihypertensive treatment was reduced and as a result OBPM was elevated in the final follow-up (the red line shown in Fig. 2 corresponds to this patient). The ABPM values were similar or slightly lower after ablation (24-h ABPM changed from 152/88 mmHg to 147/86 mmHg), indicating a white-coat syndrome component in the OBPM). This patient was the only one considered to be a nonresponder, as the other patients had decreased systolic and/or diastolic OBPM pressures. This patient was one of the 2 patients with a polar artery in one of the kidneys and the oldest in the series (65 years). The percentage of nonresponders was similar to that reported in the Symplicity HTN-2 trial.11

The results of the program were made possible by the close collaboration of physicians from different areas of expertise. The vital role of nephrologists from the hypertension unit in patient selection and management is indisputable. All the denervation procedures were performed by 2 cardiologists specializing in different areas: an interventional cardiologist and electrophysiologist. However, the participation of both specialists may not be necessary. With the aim of increasing experience and ensuring the best results, we recommend that in each center the technique should be performed by specialists who have been introduced to the technique and have performed it since its implementation. However, it seems important that potential candidates should be studied by hypertension specialists (nephrologists, cardiologists, and internists, depending on the center), in centers with experience, as recommended by the European Society of Hypertension.18

The protocol designed in our center for the selection of candidates for RD excludes most patients with poorly controlled hypertension and who are taking 3 or more drugs due to pseudoresistence or improvement after the use of aldosterone antagonists. This highlights the importance of adequate clinical assessment of patients with suspected RH before RD is indicated.

Patient selection and the procedure performed in the first denervated patients led to improved OBPM values in a number of cases and in similar numbers to those reported in previous studies, but with greater reductions in the use of antihypertensive drugs.

The authors thank the Fondation pour la prevention des maladies cardiovasculaires (Geneva, Switzerland) for financing the ablation catheters used in the study.

None declared.