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Catheter-guided renal sympathetic denervation in patients with therapy-refractory hypertension
Hypertension is the leading cause of cardiovascular disease worldwide, with a prevalence of 30–40% in the West and 20–35% in the Middle East. More than 50% of patients have inadequate blood pressure control despite combined antihypertensive medication. Reasons for the failure to achieve recommended blood pressure values include lack of patient compliance and inefficiency of antihypertensive treatment (therapy-refractory hypertension).
Percutaneous catheter-based radiofrequency ablation of the sympathetic nervous system has recently been introduced as the first non-pharmaceutical approach to treat hypertension. This therapy causes denervation of the afferent and efferent nervous system located in both renal arteries and thus reduces sympathetic overactivation, which is an important pathway in the pathophysiology of hypertension. Ablation is performed via a catheter inserted into the arterial system through a transfemoral approach. Radiofrequency energy is than applied at multiple sites in both renal arteries. This destroys the nerve fibres which spiral along the outside of the renal vessels. Animal and ‘first in human studies’ have shown that a significant drop in blood pressure can be achieved with this therapy. In 2010, Esler and the Symplicity HTN-2 study group published the immediate and 6-month results of the renal sympathetic denervation trial in the Lancet.1
The Symplicity trial was conducted as a prospective randomized study in 24 centres in Europe, Australia and New Zealand. Patients with hypertension were included if their systolic blood pressure was ≥ 160 mmHg (≥ 150 mmHg if diabetics) despite antihypertensive therapy with at least three different drugs. The study was conducted between June 2009 and January 2010. The participants were allocated in a 1:1 ratio to undergo renal denervation (without discontinuation of their medication) or to maintain their previous medication alone. Exclusion criteria were an estimated glomerular filtration rate (GFR) ≤ 45 ml/min/1.73 m2, type 1 diabetes, contraindications to magnetic resonance imaging (MRI), substantial stenotic valvular heart disease, pregnancy and history of myocardial infarction, unstable angina or cerebrovascular episodes in the previous 6 months. Furthermore, patients with significant renal artery stenosis, who had undergone a previous intervention or who were ineligible for the intervention owing to renal artery anatomy (length < 20 mm, diameter < 4 mm) were excluded. The primary endpoint was the difference in average office-based measurements of systolic blood pressure from baseline to 6 months’ follow-up between patients treated with renal denervation and patients receiving conventional antihypertensive medication.
A total of 106 patients were included in the study, of whom 52 (49%) underwent bilateral renal sympathetic denervation. Six months’ follow-up could be completed in 94% of all patients. The authors detected a mean reduction in office-based blood pressure of 32/10 mmHg (± 23/11; P < 0.0001) in the treatment group whereas they observed no significant systolic and diastolic change (P = 0.77 and P=1.00, respectively) and at 6 months’ follow-up. The investigators did not report any device-related or procedure-related complications or a significant difference in adverse events between the groups. A possible progression of an underlying atherosclerotic lesion was reported in one patient.
Clinical implications of the sympathetic renal denervation therapy
Renal denervation of the sympathetic nervous system represents a promising and safe therapeutic option in patients with therapy-resistant hypertension. The authors of the presented study were able to demonstrate a clinically relevant decrease in treatment-resistant essential hypertension. Nevertheless, it is not known to what degree regrowth of the sympathetic nerve system might weaken the treatment effect. In 2011, the study authors published their 24-months follow-up results of an extended study cohort in Hypertension and demonstrated a persisting reduction in blood pressure over this period.2 However, data from 24 months’ follow-up were available in only 18 (12%) of the initially included 150 patients at baseline. Thus, long-term data in a larger study population are still needed. Nevertheless, this landmark study warrants further studies to document not only the long-term effects of this treatment but also its mortality benefit. The early positive results of the renal denervation procedure also open up new areas of research, specifically to test the potential of renal denervation in patients with mild forms of essential hypertension or other diseases which are associated with overactivation of the sympathetic nervous system, such as cardiac failure, diabetes, arrhythmias and liver cirrhosis.
In conclusion, the publication of the Symplicity trial in the Lancet can be considered one of the major landmark studies in recent years. It shows that an interventional strategy of treating hypertension can be effective. At present renal denervation can be considered an alternative for selected patients with therapy-refractory hypertension.
- Symplicity HTNI, Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the symplicity htn-2 trial): a randomised controlled trial. Lancet. 2010;376:1903–9.
- Symplicity HTNI. Catheter-based renal sympathetic denervation for resistant hypertension: Durability of blood pressure reduction out to 24 months. Hypertension. 2011; 57:911–17.
Department of Cardiology
Vienna University Clinic