Correspondence Letter by Jin et al Regarding Article, “Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension” To the Editor: We read with interest the article by Mahfoud and colleagues.1 They classified 346 patients with uncontrolled hypertension according to their 24-hour ambulatory blood pressure (BP; threshold reported in Methods, 130 mm Hg) into 303 with true-resistant hypertension and 43 with pseudoresistant hypertension. Systolic BP in truly resistant patients averaged 172 and 154 mm Hg on office and 24-hour ambulatory measurement and 161 and 121 mm Hg in pseudoresistant patients. Mahfoud et al reported that renal denervation reduced office BP and improved aspects of ambulatory BP, commonly linked to cardiovascular risk, in truly resistant patients, whereas renal denervation only reduced office BP in pseudoresistant hypertension. A decrease in BP, being subjected to placebo effects and regression to the mean, is always more pronounced with a higher starting level.2 In our opinion, the conclusions by Mahfoud et al were therefore predictable. In our opinion, the information in the Mahfoud et al article is incomplete.1 First, the authors did not measure, but extrapolated, cardiovascular risk in relation to the ambulatory BP. Second, the proportions of patients at 3, 6, and 12 months of follow-up were only 70.8%, 68.2%, and 26.0%, with no reason given for the substantial attrition rate. Third, the authors reported that no differences existed in medication reductions (P=0.524) or increases (P=0.399) between true-resistant and pseudoresistant patients but did not report the number of antihypertensive drug classes during follow-up. Further data on the long-term efficacy and safety of renal denervation in treatmentresistant hypertension should be collected in the context of randomized, clinical trials. The Mahfoud et al article is inconsistent in the stated methods and results. For instance, there is contradiction between the abstract and the Methods section as to whether daytime as opposed to 24-hour ambulatory BP was used to classify patients. The Results refer to Figure 4 as illustrating daytime BP, whereas it is 24-hour BP according to the figure legend. Throughout the article, we found contradictions in summary statistics, which we communicated to the editors of Circulation. Based on Table 3, Mahfoud et al concluded that renal denervation was equally effective in all subgroups. However, Table 3 provides only the odds that office BP declined by ≥10 mm Hg but does not allow comparison of the BP responses between subgroups. Mahfoud et al combined data from 10 centers without adjusting for differences between centers. Finally, we2 share the concerns of the editorialist3 about the disproportionality between the responses in office and ambulatory BPs. The Dr Mahfoud’s center did >600 renal denervation procedures at a cost of 4500€ each.4 Health insurance in Germany, Sweden, Switzerland, and the Netherlands now covers renal denervation. Reimbursement of this costly and invasive procedure rests on a single randomized, clinical trial5 and the CE (Conformité

Européenne) label certification (KCE reports 158C available at https://kce.fgov.be). In conclusion, generating solid evidence proving the long-term efficacy and safety of renal denervation in treatment-resistant hypertension remains a top research priority.2

Disclosures None. Yu Jin, MD Studies Coordinating Center Research Unit Hypertension and Cardiovascular Epidemiology KU Leuven Department of Cardiovascular Sciences University of Leuven Leuven, Belgium Alexandre Persu, MD Pole of the Cardiovascular Research Institut de Recherche Expérimentale et Clinique and Division of Cardiology Cliniques Universitaires Saint-Luc Université Catholique de Louvain Brussels, Belgium Jan A. Staessen, MD Studies Coordinating Center Research Unit Hypertension and Cardiovascular Epidemiology KU Leuven Department of Cardiovascular Sciences University of Leuven Leuven, Belgium

References 1. Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, Weil J, Schmidt M, Hoppe UC, Zeller T, Bauer A, Ott C, Blessing E, Sobotka PA, Krum H, Schlaich M, Esler M, Böhm M. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation. 2013;128:132–140. 2. Persu A, Jin Y, Azizi M, Baelen M, Völz S, Elvan A, Severino F, Rosa J, Adiyaman A, Fadl Elmula FE, Taylor A, Pechère-Bertschi A, Wuerzner G, Jokhaji F, Kahan T, Renkin J, Monge M, Widimský P, Jacobs L, Burnier M, Mark PB, Kjeldsen SE, Andersson B, Sapoval M, Staessen JA; European Network Coordinating Research on Renal Denervation (ENCOReD). Blood pressure changes after renal denervation at 10 European expert centers. J Hum Hypertens. 2014;28:150–156. 3. Parati G, Ochoa JE, Bilo G. Renal sympathetic denervation and daily life blood pressure in resistant hypertension: simplicity or complexity? Circulation. 2013;128:315–317. 4. Blech J. Vergebens verbrutzelt. Der Spiegel. 2013;28:102–103. 5. Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–1909.

(Circulation. 2014;129:e499.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIRCULATIONAHA.113.005121

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Letter by Jin et al Regarding Article, ''Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension'' Yu Jin, Alexandre Persu and Jan A. Staessen Circulation. 2014;129:e499 doi: 10.1161/CIRCULATIONAHA.113.005121 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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