Reduction In Ambulatory Blood Pressure Research Articles

Aerobic versus isometric handgrip exercise in hypertension: a randomized controlled trial.

Aerobic dynamic exercise reduces blood pressure (BP) and is broadly recommended by current American and European hypertension guidelines. Isometric exercise is currently not recommended, since data from only a few studies are available. We compare for the first time the effects of isometric handgrip training and aerobic exercise in a randomized controlled trial. A total of 75 hypertensive patients were randomized to one of the following 12-week programmes: Isometric handgrip training five times weekly (two contractions of 2 min at 30% of maximal power with each arm); 'Sham-handgrip training' five times weekly (two contractions of 2 min at 5% of maximal power with each arm); Aerobic exercise training of 30 min three to five times per week. All patients underwent office BP measurement, 24-h ambulatory BP measurement and noninvasive assessment of arterial compliance and systemic vascular resistance at baseline and after 12 weeks. Baseline epidemiological and hemodynamic characteristics did not differ between groups. Aerobic exercise led to a significant reduction of systolic 24-h BP (P = 0.025), office SBP (P = 0.03), systemic vascular resistance (P = 0.001) and small artery elasticity index (P = 0.005). There were no statistical significant changes of these parameters in the isometric exercise and the 'sham exercise' groups (P > 0.05 each). Isometric handgrip training, performed according to a typical protocol, did not reduce BP in hypertensive patients. Aerobic exercise, even as an uncontrolled and unsupervised exercise regimen, led to a significant reduction of ambulatory and office BP.

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs

Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018.

Abstract P486: Effects of Isometric Leg Training on Ambulatory Blood Pressure and Morning Blood Pressure Surge in Young Normotensive Men and Women

Introduction: Cardiovascular disease (CVD) is a major cause of death globally with hypertension reported to be a leading modifiable risk factor. Ambulatory blood pressure (BP), in particular diurnal BP variability, is considered to be associated with CVD risk. In addition, the morning BP surge (MBPS) is thought to be associated with increased stroke risk and to be a destabilizing factor for atherosclerotic plaque. Isometric resistance training (IRT) is an effective method of lowering BP and has been recommended by the American Heart Association as an alternative treatment for reducing BP. To date, few studies have investigated the effects of IRT on ambulatory BP and particularly the morning surge in BP. Therefore, the purpose of this study was to determine whether (i) IRT causes reductions in ambulatory BP and the MBPS, in young normotensives and (ii) there are any sex differences in these changes. Methods: Ambulatory BP was measured prior to, and after, 10 weeks of bilateral leg IRT using an isokinetic dynamometer (4 x 2 minute contractions at 20% MVC, with 2 minute rest periods on 3 days per week). Twenty normotensive individuals (10 men, age=21 ± 4 years; 10 women, age=23 ± 5 years) were recruited. A two-way repeated measures ANOVA was used to assess the within and between groups ambulatory (mean 24-h, daytime, night time and diurnal variation) BP and MBPS. MBPS was calculated as: mean systolic BP 2 hours after waking minus the lowest sleeping 1 hour mean systolic BP. Results: There were significant reductions in 24-h ambulatory (4 ± 2 mmHg, p=0.0001; 4 ± 2 mmHg, p=0.0001) systolic BP in both men and women following IRT. This comprised significant reductions in day time (5 ± 5 mmHg, p=0.019; 5 ± 4 mmHg, p=0.002) but not night time (1 ± 5 mmHg, p=0.75; 1 ± 3 mmHg, p=0.3) systolic BP. Additionally, there were significant reductions in the MBPS (6 ± 8 mmHg, p=0.044; 6 ± 7 mmHg, p=0.019). There were no significant differences between men and women in these changes (p>0.05). Conclusion: These results support previous research showing that IRT is effective in lowering ambulatory BP. Furthermore, the significant reductions in the MBPS offer the potential for clinically meaningful CVD and stroke risk reduction, provided these effects can be demonstrated in those who are at risk.

BP.10.06] BLOOD PRESSURE RESPONSE TO CATHETER-BASED RENAL SYMPATHETIC DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while “real-world” data from registries are needed. In the present study we report the complete set of 12 month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. Design and method: In 4 Greek hospital centers 79 patients with severe drug resistant hypertension (age: 59 ± 10 years, 53 males, body mass index: 33 ± 5 kg/m2, office BP and 24-hour ambulatory BP were 176 ± 15/95 ± 13 mmHg and 155 ± 14/90 ± 12 mmHg respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Results: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 mmHg and -29/-12 mmHg, while the reduction in 24-hour ambulatory BP was −16/−9 mmHg and −15/−9 mmHg respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10 mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24 h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months there were no significant changes in renal function and no new serious device or procedure related adverse events. Conclusions: In our “real-world” multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12 months follow-up. Moreover, younger age, obesity and higher levels of baseline systolic BP are independently related to better BP response to RDN.

Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study

Background: Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial.Patients and methods: Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group.Results: The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups.Conclusion: Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

Renal denervation beyond the bifurcation: The effect of distal ablation placement on safety and blood pressure.

Renal denervation may be more effective if performed distal in the renal artery because of smaller distances between the lumen and perivascular nerves. The authors reviewed the angiographic results of 97 patients and compared blood pressure reduction in relation to the location of the denervation. No significant differences in blood pressure reduction or complications were found between patient groups divided according to their spatial distribution of the ablations (proximal to the bifurcation in both arteries, distal to the bifurcation in one artery and distal in the other artery, or distal to the bifurcation in both arteries), but systolic ambulatory blood pressure reduction was significantly related to the number of distal ablations. No differences in adverse events were observed. In conclusion, we found no reason to believe that renal denervation distal to the bifurcation poses additional risks over the currently advised approach of proximal denervation, but improved efficacy remains to be conclusively established.

A Network Meta-Analysis of Clinical Management Strategies for Treatment-Resistant Hypertension: Making Optimal Use of the Evidence

BackgroundWith the addition of surgical interventions to current medicinal treatments, it is increasingly challenging for clinicians to rationally choose among the various options for treating patients with apparent treatment-resistant hypertension (ATRHTN).This study aims to establish the comparative effectiveness of mineralocorticoid receptor antagonists (MRA), renal denervation (RDN), darusentan and central arteriovenous anastomosis (CAA) for patients with ATRHTN by performing a network meta-analysis.MethodsData Sources: Studies from recent meta-analyses for RDN and placebo effect were supplemented with a systematic search for MRAs in ATRHTN in the Pubmed, EMBASE, CINAHL and Cochrane databases through November 2016.Study Selection: Randomized controlled trials comparing treatment options for patients with ATRHTN.Data Extraction and Synthesis: Data were extracted using predefined data extraction forms, including the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. A Bayesian random effects model was used to conduct a network meta-analysis. Spironolactone was used as the main comparator.Main Outcomes and Measures: Reduction in 24-h ambulatory blood pressure measurement (ABPM).ResultsTwenty articles met our inclusion criteria, and seven treatment alternatives were compared. Compared to MRA, CAA had the highest probability of being more effective, further reducing 24-h SBP (−4.8 mmHg [−13.0, 3.7]) and 24-h DBP (−9.7 mmHg [−18, -0.63]). This difference is likely to be clinically meaningful, with a probability of 78 and 96% at a threshold of a 2-mmHg reduction in blood pressure.ConclusionsWhen compared to MRA as anchor, darusentan, CAA and RDN are not more effective in achieving a clinically significant reduction in ambulatory blood pressure in individuals with apparent treatment-resistant hypertension.

Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review

Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

240 - Ambulatory blood pressure reduction following 2 weeks of high-intensity interval training performed on ergo-cycle in water or dry land condition

240 - Ambulatory blood pressure reduction following 2 weeks of high-intensity interval training performed on ergo-cycle in water or dry land condition

Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry.

The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59±10years, 53 males, body mass index 33±5kg/m2; office BP and 24-h ambulatory BP were 176±15/95±13 and 155±14/90±12mmHg, respectively, 4.4±0.9 antihypertensive drugs) underwent RDN and were followed-up for 12months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Reduction in office systolic/diastolic BP at 6 and 12months from baseline was -30/-12 and -29/-12mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9mmHg, respectively (p<0.05 for all). Patients that were RDN responders (85%, n=58), defined as an at least 10-mmHg decrease in office systolic BP at 12months, compared to non-responders were younger (57±9 vs 65±8years, p<0.05), had higher baseline office systolic BP (176±17 vs 160±11mmHg, p<0.05) and 24-h systolic BP (159±13 vs 149±11mmHg, p<0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p<0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.

Aggressive renal sympathetic denervation approach to treating resistant hypertension: A fresh start?

A multivariable analysis identified predictors of systolic blood pressure change in SYMPLICITY HTN-3 trial. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Greater reductions in office and ambulatory systolic blood pressure, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern. Based on this information, we selected a white patient with baseline office systolic blood pressure >180 mmHg, using aldosterone antagonist, non-using vasodilators, and performed an aggressive RSD approach.Male patient, 40 years old, white, referred by the attending physician to our service due to a complaint of dyspnea, dizziness, and headache. Resistant hypertensive patient, already being tested various therapeutic regimens. The procedure did not show any vascular complications and the patient was discharged after 24 h hospitalization, clinically stable, walking without difficulty, and presenting mean office blood pressure levels during the 24 h post procedure in 130/82 mmHg. After 6 months of follow-up, the office blood pressure was 140/89 mmHg, and the 24-h ABPM values were: mean = 132/83 mmHg, awake = 135/86 mmHg, and sleeping = 126/75 mmHg, and did not present any symptoms.

PS 08-07 DIFFERENTIAL AMBULATORY BLOOD PRESSURE LOWERING EFFECT BETWEEN HYPERTENSIVE PATIENTS WITH AND WITHOUT DIABETES MELLITUS

Objective: We assessed whether there is dissociation between ambulatory blood pressure (BP) reduction and clinic BP reduction by antihypertensive medication in hypertensive patients with and without diabetes mellitus (DM). Design and Method: We formerly performed randomized, multicenter, open-label trial in essential hypertensives. 105 patients with clinic BP ≥ 140/90 mmHg with amlodipine 5 mg were randomly allocated to aliskiren (150–300 mg)/amlodipine (5mg) (ALI/AML) or high-dose amlodipine (10 mg) (h-dAML) group and were treated for 16 weeks. Ambulatory BP and clinic BP were measured at baseline and at the end of the study. In current post-hoc analysis study, we divided 86 patients (age 77.1 years) who completed treatment period into Non-DM (n = 75) or DM (n = 11) group, and compared ambulatory BP reduction and clinic BP reduction. We defined ‘DM’ as antidiabetic treated DM patients or baseline HbA1c ≥ 6.5, and ‘Non-DM’ as the other patients. No type 1 DM patient is included in this study. Results: There was no significant difference in clinic BP and ambulatory BP at baseline. The reduction of clinic SBP were similar between the Non-DM and DM group (−10.7 ± 18.7 vs. −5.8 ± 18.0 mmHg, p = 0.42), whereas the reduction of 24-h SBP (−7.7 ± 10.9 vs. 1.7 ± 11.5 mmHg, p = 0.01) and daytime SBP (−7.8 ± 13.4 vs. 3.6 ± 13.8 mmHg, p = 0.01) were significantly smaller in the DM group than in the Non-DM group. 24-h SBP and daytime SBP were significantly decreased by treatment only in the Non-DM group. Conclusions: Although the magnitude of clinic SBP reduction were similar, 24-h SBP reduction and daytime SBP reduction were significantly smaller in DM compared with in Non-DM. Our data suggest that ambulatory BP reduction by antihypertensive medication is insufficient in hypertensive patients with DM.

PS 11-83 ONE-YEAR OUTCOMES OF THE RANDOMIZED OSLO-RDN STUDY

Objective: The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment resistant hypertension (TRH) shows variation among the few randomized studies. The duration of antihypertensive effect and long-term effect and safety of RDN require further follow-up. We aimed to report the office and ambulatory (BP) changes and long-term safety at 12-month follow-up. Design and Method: Patients with apparent TRH (n = 65) were referred specifically for RDN and those with secondary and spurious hypertension (n = 26) were excluded. TRH was defined as office systolic BP>140 mmHg despite maximally tolerated doses of at least 3 antihypertensive drugs including a diuretic. Additionally, ambulatory daytime systolic BP > 135 mmHg following witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP, indicating poor drug adherence. Patients with true TRH were randomized and underwent RDN with Symplicity catheter (n = 9) versus adjusted drug treatment (n = 10). Results: 24-hour ambulatory systolic and diastolic BPs in the drug adjustment group changed from 151 ± 13/84 ± 7 mmHg (±SD) at baseline to 131 ± 12/75 ± 5 mmHg at 12 months (p < 0.0005 for all), and in the RDN group from 149 ± 9/89 ± 7 to 141 ± 11/83 ± 5 mmHg (p = 0.07 and p = 0.04, respectively). The absolute difference in change between groups in systolic BP was significantly higher in favor of the drug adjustment group (p = 0.01). Office, daytime and nighttime ambulatory BPs changed in parallel to the 24-hour ambulatory BPs. However 2 patients in RDN group considered as a responder since they have sustained reduction of 24-hour ambulatory systolic BP by more than 15 mmHg. There were no significant changes in renal arteries assessed by MRI or CT scans after 12 months follow-up. No deterioration of renal function was found. Conclusions: RDN has inferior BP lowering effects compared to adjusted drug treatment in patients with TRH. However, RDN is safe and this encourages future research to identify characteristics of patients who might respond to RDN.

Unilateral Carotid Body Resection in Resistant Hypertension: A Safety and Feasibility Trial

SummaryAnimal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible. Overall, no change in blood pressure was found. However, 8 patients showed significant reductions in ambulatory blood pressure coinciding with decreases in sympathetic activity. The carotid body may be a novel target for treating an identifiable subpopulation of humans with hypertension.

Dose-effect relationship of perindopril 10, 14 and 20 mg assessed by urine and plasma AcSDKP levels in mildly sodium-depleted healthy volunteers

BackgroundWe describe a pharmacodynamic study of the dose-effect relationship of perindopril arginine at 10, 14, and 20mg with in vivo angiotensin-converting enzyme (ACE) activity, assessed by urine and plasma AcSDKP levels, as well as the effect on plasma active renin concentrations and blood pressure. MethodsThis randomized, double-blind, four-period, crossover study involved single-dose administration of perindopril arginine (10, 14, and 20mg or placebo) to 32 healthy male normotensive mildly sodium-depleted volunteers. Blood and urine were collected over 48h for AcSDKP, ACE activity, and plasma active renin measurements. ResultsThere were dose-related increases in urinary AcSDKP excretion and plasma AcSDKP concentration after administration of perindopril, with significant between-period differences (estimate of the median difference in urinary excretion over 48h of AcSDKP, 49.1 [95% CI: 15.3–82.0] nmol for 14 versus 10mg, and 73.2 [95% CI: 44.9–106.3] nmol for 20 versus 14mg). Consequently, a dose-dependent increase in plasma active renin concentration was observed. Even though each dose of perindopril 10 to 20mg was associated with a significant 24-h ambulatory blood pressure reduction versus placebo, no dose-dependency was detected in these normotensive subjects. ConclusionsAdministration of perindopril arginine 10, 14, or 20mg to mildly sodium-depleted healthy volunteers is associated with a dose-dependent inhibition of in vivo ACE activity with significant between-dose differences. This effect was associated with a dose-dependent increase in plasma active renin concentration, indicating a dose-dependent blockade of the renin angiotensin system.

Initial Experience with Renal Denervation for the Treatment of Resistant Hypertension - The Utility of Novel Anesthetics and Metaiodobenzylguanidine Scintigraphy (MIBG).

Background:The Symplicity-HTN 3 trial failed to show significant difference in blood pressure (BP) lowering between patients undergoing catheter-based renal denervation (RDN) and the sham-procedure arm of the study. However, there is still optimism about the role of RDN in the treatment of resistant hypertension, because identification of patients with increased sympathetic activity thus being good RDN responders, improvements in the RDN procedure and new technology RDN catheters are all expected to lead to better RDN results. We present our initial experience with RDN for the treatment of resistant hypertension, and the utility of novel anesthetics and cardiac 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG).Methods and Results:Seven patients with resistant hypertension underwent RDN and were followed up for 6 months. MIBG was performed before RDN, in order to estimate sympathetic activity and predict the response to RDN. All patients were sedated with dexmedetomidine and remifentanil during RDN. All patients tolerated the procedure well, were hemodynamically stable and their peri-procedural pain was effectively controlled. A median of 7.6 ± 2.1 and 6 ± 1.4 ablations were delivered in the right and left renal artery respectively, making an average of 6.8 burns per artery. No peri-procedural or late complications - adverse events (local or systematic) occurred. At 6 months, mean reduction in office BP was -26.0/-16.3 mmHg (p=0.004/p=0.02), while mean reduction in ambulatory BP was -12.3/-9.2 mmHg (p=0.118/p=0.045). One patient (14.3%) was a non-responder. None of the cardiac 123I-MIBG imaging indexes(early and late heart-to-mediastinum (H/M) count density ratio, washout rate (WR) of the tracer from the myocardium) were different between responders and non-responders.Conclusion:Patients with resistant hypertension who underwent RDN in our department had a significant reduction in BP 6 months after the intervention. 123I-MIBG was not useful in predicting RDN response. Dexmedetomidine and remifentanil provided sufficient patient comfort during the procedure, allowing an adequate number of ablations per renal artery to be performed, and this could probably lead to improved RDN results.

Impact of Introducing Catheter-based Renal Denervation into Japan for Hypertension Management: Estimation of Number of Target Patients and Clinical Relevance of Ambulatory Blood Pressure Reduction.

New medical approaches to the autonomic nervous system, such as catheterbased renal denervation, have been introduced into clinical practice in the recent years for patients who have resistant hypertension. We estimate the number of subjects in Japan who would benefit from renal denervation when this treatment is introduced into Japan, based on data from the Jichi Medical University clinical trials. We also discuss the logical basis of changing the formerly used primary endpoint, i.e., office BP, to 24-hr ambulatory BP in future clinical trials. Among JAMP registry data, the total number of hypertensives was 5,858 and the patients who were prescribed ≥ 3 drugs including diuretics were 749. The poorly controlled hypertension rate was 32% in the group prescribed ≥ 3 drugs including diuretics and it constitutes 4.1% of the total hypertensive patients. We also analyzed the data of JMS ABPM cohort study wave 1 (811 patients). The hazard ratios (HRs) for each 10-mmHg increase in BP was 1.38 (95%CI 1.17-1.63, p&lt;0.001) for 24-hr BP and 1.18 (95%CI 1.05-1.33, p=0.006) for office BP. However, the significance for office BP was lost once the 24-hr, daytime and nighttime ambulatory BP data were added to the covariates. The prevalence of resistant hypertensive patients among all of the hypertensive patients is 4.1%. Based on this prevalence, the number of resistant hypertensive individuals in Japan would be 1,870,000 patients. In future renal denervation clinical studies in Japan, we should set the primary endpoint as a 24-hr systolic BP reduction measured by ABPM.

Renal denervation with standard radiofrequency ablation catheter is effective in 24-hour ambulatory blood pressure reduction - follow-up at 1/3/6/12months.

AimsTo examine the effect of renal denervation (RDN) on 24‑h ambulatory blood pressure (ABP) with a standard radiofrequency ablation catheter (RF catheter).MethodsSeventy-five patients with resistant hypertension received bilateral RDN with an RF catheter (6 RF applications, 1 minute each, 8–12 watts). Seventy patients fulfilled inclusion criteria with mean systolic ABP ≥140 mmHg (mean 165/89) despite treatment with ≥3 antihypertensive drugs (mean 5.9) including a diuretic, and were further analysed for ABP changes. Follow-up at 1/3/6/12 months comprised biochemical evaluations and ABP measurement. At 6/12 months, duplex sonography of the renal arteries was additionally performed.ResultsAt 1/3/6/12 months we observed a significant reduction in systolic ABP of −15/−17/−18/−15 mmHg (n = 55/53/57/50; non-parametric Friedman test, p < 0.001) and diastolic ABP of −6/−9/−10/−7 mmHg (p < 0.001). Of the patients, 70 %/64 % showed a systolic ABP reduction of ≥10 mmHg, and 77 %/70 % of ≥5 mmHg at 6/12-month follow-up. Two patients (2.7 %) developed renal artery stenosis (>70 %) with subsequent stenting without complications. Logistic regression analysis with systolic ABP reduction ≥10 mmHg at 12 months follow-up as criterion revealed that only the mean baseline systolic ABP was significant, OR = 2.174.ConclusionsRDN with a standard RF catheter can be used safely to reduce mean ABP in resistant hypertension as shown in long-term follow-up.

Office and ambulatory blood pressure control in hypertensive patients treated with different two-drug and three-drug combinations

ABSTRACTThere is scarce information regarding ambulatory blood pressure (BP) achieved in daily practice with a wide range of antihypertensive drug combinations. We looked for differences in office and ambulatory BP among major drug combinations of two and three antihypertensive agents from a different drugs class. A total of 17187 patients treated with six types of two-drug combinations and 9724 treated with six types of three-drug combinations from the Spanish ABPM Registry were analyzed. We compared achieved office and ambulatory BP, as well as office (< 140/90 mmHg) and ambulatory (24-hour BP < 130/80; day BP < 135/85, and night BP < 120/70 mmHg) BP control among groups. The combination of renin-angiotensin system (RAS) blockers with diuretics and the triple combination of RAS blockers with diuretics and calcium channel blockers (CCB) were associated with lower values of 24-hour, daytime and nighttime BP, as well as more pronounced nocturnal BP dip. Compared with such combinations (reference), other double combinations had lower rates of ambulatory BP control. Moreover, triple combinations containing alpha blockers also had lower rates of ambulatory BP control. We conclude that even with similar office BP control, differences exist among antihypertensive two-drug and three-drug combinations with respect to ambulatory BP control achieved during treatment, with RAS blockers/diuretics and RAS blockers/CCBs/diuretics obtaining better control rates. This can help physicians choose among drug combinations in order to obtain further ambulatory BP reductions.