Renal Denervation in Moderate Treatment-Resistant Hypertension
In this investigator-initiated, prospective, multicenter pilot study, 54 adult patients with TRH defined by JNC-7 and ESH/ESC, guidelines were consecutively included if the patient's office BP was ≥140/90 mm Hg and <160/100 mm Hg. In addition, in every patient, true resistant hypertension was confirmed by initial 24-h ABPM (≥130/80 mm Hg), thereby excluding "white coat" (elevated office BP, but normal values out of the office, either on ABPM or home blood pressure monitoring [HBPM]) or pseudoresistant hypertension; but in contrast to Symplicity HTN-2 trial, no home BP measurement for 2 weeks was required. Patients were required to be on an unchanged antihypertensive drug regimen for at least 2 months, without any allowance for dose or regimen adjustments. Thus, office BP measurements and 24-h ABPM were taken under stable conditions. Main exclusion criteria were renal artery anatomy (main renal arteries <4 mm in diameter or <20 mm in length, hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery, history of renal artery intervention including balloon angioplasty or stenting, multiple main renal arteries in either kidney) and any secondary cause of hypertension, except for treated obstructive sleep apnea syndrome and chronic kidney disease. Altogether, 19% of patients referred to our tertiary universities' outpatient clinics were eligible for this pilot study and were treated between February 2011 and March 2012. The study protocol was approved by the local ethics committees from the 2 participating centers, and the study was performed according to Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all patients before study entry. The study was registered at U.S. National Institutes of Health Clinical Trials website (NCT01687725).
Office BP was measured in both arms after 5 min of rest in a sitting position, with an oscillometric device (study center Erlangen: Dinamap Pro100V2 [Criticon, Norderstedt, Germany]; study center Homburg/Saar: Omron HEM-705 monitor [Omron Healthcare, Vernon Hills, Illinois], with a printer for documentation). Subsequent BP measurements were made in the arm with the higher BP reading, and the average of the last 3 measurements was taken. Ambulatory 24-h BP measurements were taken with an automatic portable device that was validated according the ESH International Protocol (e.g., Spacelab no. 90207, Redmont, California) prior to RDN. Twelve patients refused ABPM, and in 6 patients, data readings were insufficient (in 5 cases there were no nighttime recordings; and in 1 case, recordings <80% successful were obtained) 6 months after RDN. Hence, in a subgroup (n = 36), successful ABPM was measured 6 months after RDN. In every patient, the same device was used before and 6 months after RDN. Patients were divided according their dipping pattern into "dippers" (night-time BP fall >10%) and "non-dippers" (night-time BP fall <10%).
Heart rate was obtained using 12-lead electrocardiography, performed 10 min after supine rest at standard sensitivity (10 mm = 1 mV) and a paper speed of 50 mm/s.
For RDN, the femoral artery was accessed with standard endovascular technique. Radiofrequency catheter (Symplicity RDN system, Medtronic Inc.) was advanced in each renal artery by angiography. As described previously in detail, at least 4 radiofrequency ablations (energy delivery for 120 s each), controlled and regulated by a radiofrequency generator, were applied within the lengths of each renal artery. Patients received 5,000 IU of heparin to achieve an activated clotting time of >250 s. Diffuse visceral pain during the procedure was managed with anxiolytics and narcotics.
All analyses were performed using SPSS version 19.0 software (SPSS Inc., Chicago, Illinois). Normal distribution of data was confirmed by Kolmogorov-Smirnov test before further analyses. Data were compared by paired and unpaired Student t-tests and by Wilcoxon and McNemar tests where appropriate. Data are mean ± SD. Univariate correlation was performed using the Pearson correlation coefficient. A two-sided p value of <0.05 was considered statistically significant.
Methods
Study Cohort and Design
In this investigator-initiated, prospective, multicenter pilot study, 54 adult patients with TRH defined by JNC-7 and ESH/ESC, guidelines were consecutively included if the patient's office BP was ≥140/90 mm Hg and <160/100 mm Hg. In addition, in every patient, true resistant hypertension was confirmed by initial 24-h ABPM (≥130/80 mm Hg), thereby excluding "white coat" (elevated office BP, but normal values out of the office, either on ABPM or home blood pressure monitoring [HBPM]) or pseudoresistant hypertension; but in contrast to Symplicity HTN-2 trial, no home BP measurement for 2 weeks was required. Patients were required to be on an unchanged antihypertensive drug regimen for at least 2 months, without any allowance for dose or regimen adjustments. Thus, office BP measurements and 24-h ABPM were taken under stable conditions. Main exclusion criteria were renal artery anatomy (main renal arteries <4 mm in diameter or <20 mm in length, hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery, history of renal artery intervention including balloon angioplasty or stenting, multiple main renal arteries in either kidney) and any secondary cause of hypertension, except for treated obstructive sleep apnea syndrome and chronic kidney disease. Altogether, 19% of patients referred to our tertiary universities' outpatient clinics were eligible for this pilot study and were treated between February 2011 and March 2012. The study protocol was approved by the local ethics committees from the 2 participating centers, and the study was performed according to Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all patients before study entry. The study was registered at U.S. National Institutes of Health Clinical Trials website (NCT01687725).
Office and 24-h Ambulatory BP
Office BP was measured in both arms after 5 min of rest in a sitting position, with an oscillometric device (study center Erlangen: Dinamap Pro100V2 [Criticon, Norderstedt, Germany]; study center Homburg/Saar: Omron HEM-705 monitor [Omron Healthcare, Vernon Hills, Illinois], with a printer for documentation). Subsequent BP measurements were made in the arm with the higher BP reading, and the average of the last 3 measurements was taken. Ambulatory 24-h BP measurements were taken with an automatic portable device that was validated according the ESH International Protocol (e.g., Spacelab no. 90207, Redmont, California) prior to RDN. Twelve patients refused ABPM, and in 6 patients, data readings were insufficient (in 5 cases there were no nighttime recordings; and in 1 case, recordings <80% successful were obtained) 6 months after RDN. Hence, in a subgroup (n = 36), successful ABPM was measured 6 months after RDN. In every patient, the same device was used before and 6 months after RDN. Patients were divided according their dipping pattern into "dippers" (night-time BP fall >10%) and "non-dippers" (night-time BP fall <10%).
Heart rate was obtained using 12-lead electrocardiography, performed 10 min after supine rest at standard sensitivity (10 mm = 1 mV) and a paper speed of 50 mm/s.
Catheter-based Renal Denervation
For RDN, the femoral artery was accessed with standard endovascular technique. Radiofrequency catheter (Symplicity RDN system, Medtronic Inc.) was advanced in each renal artery by angiography. As described previously in detail, at least 4 radiofrequency ablations (energy delivery for 120 s each), controlled and regulated by a radiofrequency generator, were applied within the lengths of each renal artery. Patients received 5,000 IU of heparin to achieve an activated clotting time of >250 s. Diffuse visceral pain during the procedure was managed with anxiolytics and narcotics.
Statistical Analyses
All analyses were performed using SPSS version 19.0 software (SPSS Inc., Chicago, Illinois). Normal distribution of data was confirmed by Kolmogorov-Smirnov test before further analyses. Data were compared by paired and unpaired Student t-tests and by Wilcoxon and McNemar tests where appropriate. Data are mean ± SD. Univariate correlation was performed using the Pearson correlation coefficient. A two-sided p value of <0.05 was considered statistically significant.
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