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Michael Bohm - One of the best experts on this subject based on the ideXlab platform.

  • Renal Denervation: Is It Ready for Prime Time?
    Current Cardiology Reports, 2019
    Co-Authors: Lucas Lauder, Felix Mahfoud, Milan Wolf, Sean S. Scholz, Mathias Hohl, Michael Bohm
    Abstract:

    Purpose of Review Interventional cardiology and in particular the field of renal Denervation is subject to constant change. This review provides an up to date overview of renal Denervation trials and an outlook on what to expect in the future.

  • the spyral htn global clinical trial program rationale and design for studies of renal Denervation in the absence spyral htn off med and presence spyral htn on med of antihypertensive medications
    American Heart Journal, 2016
    Co-Authors: David E Kandzari, Raymond R Townsend, Sidney Cohen, Kazuomi Kario, Felix Mahfoud, Garrett Pilcher, Stuart J Pocock, Michael A Weber, Michael Bohm
    Abstract:

    Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal Denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal Denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal Denervation efficacy. The 2 initial trials of the program focus on the effect of renal Denervation using the Symplicity Spyral multielectrode renal Denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal Denervation or sham procedure. Both studies allow renal Denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal Denervation.

  • Procedural Aspects of Renal Sympathetic Denervation
    Updates in Hypertension and Cardiovascular Protection, 2016
    Co-Authors: Ina Zivanovic, Michael Bohm, Sebastian Ewen, Felix Mahfoud
    Abstract:

    Renal sympathetic Denervation (RDN) has, until recently, been a black box procedure, driven by incomplete knowledge on the anatomy of the sympathetic nervous system. In recent years, several procedural advancements have been made. The distribution of sympathetic nerves in the relation to the renal arteries has been further analyzed. The impact of different lesion sites, lesion numbers, and patterns has been evaluated. The spectrum of Denervation techniques and systems has been expanded and adjusted according to new anatomical findings. In addition, possibilities of intra-procedural efficacy evaluation are being developed. The following chapter summarizes our current knowledge and recent developments on procedural aspects of renal Denervation. It then outlines steps prior, during, and post procedure with instructions on the commercially available renal Denervation systems.

  • Renal Denervation for Chronic Heart Failure
    Updates in Hypertension and Cardiovascular Protection, 2016
    Co-Authors: Michael Bohm, Ina Zivanovic, Sebastian Ewen, Felix Mahfoud
    Abstract:

    In heart failure, the activation of the sympathetic nervous system is associated with a progression of the syndrome, but also with cardiovascular hospitalization and death. Renal Denervation has shown to be effective in certain patients with resistant hypertension and metabolic syndrome also associated with sympathetic overdrive. In heart failure, pilot trials with renal Denervation were initiated. Interestingly, frequent comorbidities like obstructive sleep apnea, metabolic disease, and arrhythmias could be targets, although the evidence was mainly generated in resistant hypertension. Therefore, renal Denervation in heart failure is worth to be investigated, although its effectiveness still has to be scrutinized.

  • catheter based renal Denervation for treatment of patients with treatment resistant hypertension 36 month results from the symplicity htn 2 randomized clinical trial
    European Heart Journal, 2014
    Co-Authors: Michael Bohm, Felix Mahfoud, Henry Krum, Roland E Schmieder, Horst Sievert, C L Rump, Markus P Schlaich
    Abstract:

    Aim The aim of this study was to determine long-term results of renal artery Denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study. Methods SYMPLICITY HTN-2 randomized 106 subjects with treatment-resistant hypertension to renal Denervation or medical therapy alone. At 6 months, 37 control subjects crossed over to renal Denervation. Office blood pressure measurements, antihypertensive medication use, and safety events were followed every 6 months through 3 years. Results Follow-up was available at 36 months in 40 of 52 subjects in the initial renal Denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal Denervation at 6 months. Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg (95% CI: −40, −27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95% CI: −16, −10, P < 0.01). The systolic and diastolic blood pressure reduction at 36 months for the initial renal Denervation group was −33 mmHg (95% CI: −40, −25, P < 0.01) and −14 mmHg (95% CI: −17, −10, P < 0.01), respectively. Procedural complications included one haematoma, and one renal artery dissection before energy delivery that was treated successfully. Later complications included two cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and three deaths. Conclusion Renal Denervation resulted in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe, treatment-resistant hypertension without serious safety concerns. Clinical trial registration NCT00888433.

George L Bakris - One of the best experts on this subject based on the ideXlab platform.

  • Renal Denervation: a Field in Flux
    Current Hypertension Reports, 2016
    Co-Authors: Luke J. Laffin, George L Bakris
    Abstract:

    SYMPLICITY HTN-3 was a pivotal moment for renal Denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the negative results of the first sham-controlled trial of renal Denervation. Reevaluation of the renal Denervation procedure demonstrated that a more precise approach was needed to adequately denervate the kidney. This new approach has been implemented in two ongoing clinical trials, one on and one off medications to assess the new procedure’s efficacy and safety. These and other ongoing trials will be discussed in the context of older studies in this field. We focus on novel findings published following the release of SYMPLICITY HTN-3 data in early 2014 and look to the future of renal Denervation in the treatment of primary hypertension.

  • 12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon
    Abstract:

    Abstract Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure. Objectives This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original Denervation group, the sham subjects who underwent Denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo Denervation after 6 months (non-crossover group). Methods Eligible subjects were randomized 2:1 to Denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo Denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. Results The 12-month follow-up was available for 319 of 361 Denervation subjects and 48 of 101 non-crossover subjects; 6-month Denervation follow-up was available for 93 of 101 crossover subjects. In Denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (−15.5 ± 24.1 mm Hg vs. −18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by −32.9 ± 28.1 mm Hg at 6 months, but this response regressed to −21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. Conclusions These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )

  • original investigation12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri
    Abstract:

    Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure.

  • The Future of Renal Denervation in Resistant Hypertension
    Current Hypertension Reports, 2014
    Co-Authors: Sandeep Nathan, George L Bakris
    Abstract:

    Resistant hypertension, defined as inadequate blood pressure control despite three or more antihypertensive medications at maximally tolerated doses, is strongly linked to increased cardiovascular morbidity and mortality. Increased renal afferent and efferent sympathetic activity carried by nerves which arborize the adventitia of the renal arteries, appears to be central to the pathobiology of resistant hypertension. Historical experience indicates that surgical Denervation and/or sympathectomy often dramatically reduced blood pressure in patients with malignant hypertension. Catheter-based radio-frequency renal Denervation was developed in the past decade as a percutaneous adaptation of surgical Denervation. Percutaneous renal Denervation using a variety of systems has demonstrated to date, in non-randomized and unblinded studies, dramatic reductions in office-based blood pressure, but more modest impact on ambulatory blood pressure. The only single, appropriately powered, blinded, sham-controlled study of renal Denervation conducted to date, however, failed to meet its primary endpoint, casting doubt on the value of the therapy. Ancillary benefits of renal Denervation have been described in such conditions as diabetes mellitus, heart failure, and sleep apnea but require further study. While renal Denervation is already widely available outside of the USA for commercial use, its utility in resistant hypertension must be vetted by further rigorous investigation before its use can be routinely recommended.

  • impact of renal Denervation on 24 hour ambulatory blood pressure results from symplicity htn 3
    Journal of the American College of Cardiology, 2014
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri, Manuela Negoita
    Abstract:

    Abstract Background Prior studies of catheter-based renal artery Denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. Objectives SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal Denervation or a sham procedure on ABPM measurements 6 months post-randomization. Methods Patients with resistant hypertension were randomized 2:1 to renal Denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. Results The 24-h ambulatory SBP changed −6.8 ± 15.1 mm Hg in the Denervation group and −4.8 ± 17.3 mm Hg in the sham group: difference of −2.0 mm Hg (95% confidence interval [CI]: −5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was −1.1 (95% CI: −4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was −3.3 (95 CI: −6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the Denervation group and 15.0% in the sham group (95% CI: −3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was −1.4 ± 7.4 in the Denervation group and −1.3 ± 7.3 in the sham group; (95% CI: −1.5 to 1.4; p = 0.94). Conclusions This trial did not demonstrate a benefit of renal artery Denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )

David E Kandzari - One of the best experts on this subject based on the ideXlab platform.

  • catheter based renal Denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications spyral htn off med a randomised sham controlled proof of concept trial
    The Lancet, 2017
    Co-Authors: Raymond R Townsend, David E Kandzari, Kazuomi Kario, Felix Mahfoud, Stuart J Pocock, Michael A Weber, Sebastian Ewen, Konstantinos Tsioufis, D Tousoulis
    Abstract:

    Summary Background Previous randomised renal Denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal Denervation on blood pressure in the absence of antihypertensive medications. Methods SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal Denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Findings Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal Denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal Denervation group: 24-h SBP −5·5 mm Hg (95% CI −9·1 to −2·0; p=0·0031), 24-h DBP −4·8 mm Hg (−7·0 to −2·6; p Interpretation Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal Denervation. Funding Medtronic.

  • the spyral htn global clinical trial program rationale and design for studies of renal Denervation in the absence spyral htn off med and presence spyral htn on med of antihypertensive medications
    American Heart Journal, 2016
    Co-Authors: David E Kandzari, Raymond R Townsend, Sidney Cohen, Kazuomi Kario, Felix Mahfoud, Garrett Pilcher, Stuart J Pocock, Michael A Weber, Michael Bohm
    Abstract:

    Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal Denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal Denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal Denervation efficacy. The 2 initial trials of the program focus on the effect of renal Denervation using the Symplicity Spyral multielectrode renal Denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal Denervation or sham procedure. Both studies allow renal Denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal Denervation.

  • 12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon
    Abstract:

    Abstract Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure. Objectives This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original Denervation group, the sham subjects who underwent Denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo Denervation after 6 months (non-crossover group). Methods Eligible subjects were randomized 2:1 to Denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo Denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. Results The 12-month follow-up was available for 319 of 361 Denervation subjects and 48 of 101 non-crossover subjects; 6-month Denervation follow-up was available for 93 of 101 crossover subjects. In Denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (−15.5 ± 24.1 mm Hg vs. −18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by −32.9 ± 28.1 mm Hg at 6 months, but this response regressed to −21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. Conclusions These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )

  • original investigation12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri
    Abstract:

    Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure.

  • impact of renal Denervation on 24 hour ambulatory blood pressure results from symplicity htn 3
    Journal of the American College of Cardiology, 2014
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri, Manuela Negoita
    Abstract:

    Abstract Background Prior studies of catheter-based renal artery Denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. Objectives SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal Denervation or a sham procedure on ABPM measurements 6 months post-randomization. Methods Patients with resistant hypertension were randomized 2:1 to renal Denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. Results The 24-h ambulatory SBP changed −6.8 ± 15.1 mm Hg in the Denervation group and −4.8 ± 17.3 mm Hg in the sham group: difference of −2.0 mm Hg (95% confidence interval [CI]: −5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was −1.1 (95% CI: −4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was −3.3 (95 CI: −6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the Denervation group and 15.0% in the sham group (95% CI: −3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was −1.4 ± 7.4 in the Denervation group and −1.3 ± 7.3 in the sham group; (95% CI: −1.5 to 1.4; p = 0.94). Conclusions This trial did not demonstrate a benefit of renal artery Denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )

Markus P Schlaich - One of the best experts on this subject based on the ideXlab platform.

  • reinnervation of renal afferent and efferent nerves at 5 5 and 11 months after catheter based radiofrequency renal Denervation in sheep
    Hypertension, 2015
    Co-Authors: Lindsea C Booth, Erika E Nishi, Rohit Ramchandra, Gavin W Lambert, Markus P Schlaich
    Abstract:

    Previous studies indicate that catheter-based renal Denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal Denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after Denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after Denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene–related peptide), as well as renal norepinephrine levels, was normal 11 months after Denervation. Findings at 5.5 months after Denervation were similar (n=5). In summary, catheter-based renal Denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after Denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after Denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal Denervation in human resistant hypertension need to be reassessed.

  • catheter based renal Denervation for treatment of patients with treatment resistant hypertension 36 month results from the symplicity htn 2 randomized clinical trial
    European Heart Journal, 2014
    Co-Authors: Michael Bohm, Felix Mahfoud, Henry Krum, Roland E Schmieder, Horst Sievert, C L Rump, Markus P Schlaich
    Abstract:

    Aim The aim of this study was to determine long-term results of renal artery Denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study. Methods SYMPLICITY HTN-2 randomized 106 subjects with treatment-resistant hypertension to renal Denervation or medical therapy alone. At 6 months, 37 control subjects crossed over to renal Denervation. Office blood pressure measurements, antihypertensive medication use, and safety events were followed every 6 months through 3 years. Results Follow-up was available at 36 months in 40 of 52 subjects in the initial renal Denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal Denervation at 6 months. Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg (95% CI: −40, −27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95% CI: −16, −10, P < 0.01). The systolic and diastolic blood pressure reduction at 36 months for the initial renal Denervation group was −33 mmHg (95% CI: −40, −25, P < 0.01) and −14 mmHg (95% CI: −17, −10, P < 0.01), respectively. Procedural complications included one haematoma, and one renal artery dissection before energy delivery that was treated successfully. Later complications included two cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and three deaths. Conclusion Renal Denervation resulted in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe, treatment-resistant hypertension without serious safety concerns. Clinical trial registration NCT00888433.

  • renal sympathetic Denervation for treatment of drug resistant hypertension one year results from the symplicity htn 2 randomized controlled trial
    Circulation, 2012
    Co-Authors: Murray Esler, Markus P Schlaich, Michael Bohm, Henry Krum, Roland E Schmieder, Paul A Sobotka
    Abstract:

    Background—Renal sympathetic nerve activation contributes to the pathogenesis of hypertension. Symplicity HTN-2, a multicenter, randomized trial, demonstrated that catheter-based renal Denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control, medication-only patients. Longer-term follow-up, including 6-month crossover results, is now presented. Methods and Results—Eligible patients were on 3 antihypertensive drugs and had a baseline systolic blood pressure 160 mm Hg (150 mm Hg for type 2 diabetics). After the 6-month primary end point was met, renal Denervation in control patients was permitted. One-year results on patients randomized to immediate renal Denervation (n47) and 6-month postprocedure results for crossover patients are presented. At 12 months after the procedure, the mean fall in office systolic blood pressure in the initial renal Denervation group (28.1 mm Hg; 95% confidence interval, 35.4 to 20.7; P0.001) was similar to the 6-month fall (31.7 mm Hg; 95% confidence interval, 38.3 to 25.0; P0.16 versus 6-month change). The mean systolic blood pressure of the crossover group 6 months after the procedure was significantly lowered (from 190.019.6 to 166.324.7 mm Hg; change, 23.727.5; P0.001). In the crossover group, there was 1 renal artery dissection during guide catheter insertion, before Denervation, corrected by renal artery stenting, and 1 hypotensive episode, which resolved with medication adjustment. Conclusions—Control patients who crossed over to renal Denervation with the Symplicity system had a significant drop in blood pressure similar to that observed in patients receiving immediate Denervation. Renal Denervation provides safe and sustained reduction of blood pressure to 1 year. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00888433. (Circulation. 2012;126:2976-2982.)

  • renal sympathetic Denervation in patients with treatment resistant hypertension the symplicity htn 2 trial a randomised controlled trial
    The Lancet, 2010
    Co-Authors: Murray Esler, Markus P Schlaich, Felix Mahfoud, Michael Bohm, Paul A Sobotka, Henry Krum, Roland E Schmieder, Horst Sievert, Nina Wunderlich, Lars Christian Rump
    Abstract:

    Summary Background Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal Denervation for reduction of blood pressure in patients with treatment-resistant hypertension. Methods In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal Denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov , number NCT00888433 . Findings 106 (56%) of 190 patients screened for eligibility were randomly allocated to renal Denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal Denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal Denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p Interpretation Catheter-based renal Denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients. Funding Ardian.

Raymond R Townsend - One of the best experts on this subject based on the ideXlab platform.

  • catheter based renal Denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications spyral htn off med a randomised sham controlled proof of concept trial
    The Lancet, 2017
    Co-Authors: Raymond R Townsend, David E Kandzari, Kazuomi Kario, Felix Mahfoud, Stuart J Pocock, Michael A Weber, Sebastian Ewen, Konstantinos Tsioufis, D Tousoulis
    Abstract:

    Summary Background Previous randomised renal Denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal Denervation on blood pressure in the absence of antihypertensive medications. Methods SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal Denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Findings Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal Denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal Denervation group: 24-h SBP −5·5 mm Hg (95% CI −9·1 to −2·0; p=0·0031), 24-h DBP −4·8 mm Hg (−7·0 to −2·6; p Interpretation Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal Denervation. Funding Medtronic.

  • the spyral htn global clinical trial program rationale and design for studies of renal Denervation in the absence spyral htn off med and presence spyral htn on med of antihypertensive medications
    American Heart Journal, 2016
    Co-Authors: David E Kandzari, Raymond R Townsend, Sidney Cohen, Kazuomi Kario, Felix Mahfoud, Garrett Pilcher, Stuart J Pocock, Michael A Weber, Michael Bohm
    Abstract:

    Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal Denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal Denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal Denervation efficacy. The 2 initial trials of the program focus on the effect of renal Denervation using the Symplicity Spyral multielectrode renal Denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal Denervation or sham procedure. Both studies allow renal Denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal Denervation.

  • 12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon
    Abstract:

    Abstract Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure. Objectives This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original Denervation group, the sham subjects who underwent Denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo Denervation after 6 months (non-crossover group). Methods Eligible subjects were randomized 2:1 to Denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo Denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. Results The 12-month follow-up was available for 319 of 361 Denervation subjects and 48 of 101 non-crossover subjects; 6-month Denervation follow-up was available for 93 of 101 crossover subjects. In Denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (−15.5 ± 24.1 mm Hg vs. −18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by −32.9 ± 28.1 mm Hg at 6 months, but this response regressed to −21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. Conclusions These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )

  • original investigation12 month blood pressure results of catheter based renal artery Denervation for resistant hypertension the symplicity htn 3 trial
    Journal of the American College of Cardiology, 2015
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sandeep Brar, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri
    Abstract:

    Background Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal Denervation for treatment-resistant hypertension at 6 months post procedure.

  • impact of renal Denervation on 24 hour ambulatory blood pressure results from symplicity htn 3
    Journal of the American College of Cardiology, 2014
    Co-Authors: George L Bakris, Raymond R Townsend, John M Flack, Sidney Cohen, Ralph B Dagostino, David E Kandzari, Barry T Katzen, Martin B Leon, Laura Mauri, Manuela Negoita
    Abstract:

    Abstract Background Prior studies of catheter-based renal artery Denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. Objectives SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal Denervation or a sham procedure on ABPM measurements 6 months post-randomization. Methods Patients with resistant hypertension were randomized 2:1 to renal Denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. Results The 24-h ambulatory SBP changed −6.8 ± 15.1 mm Hg in the Denervation group and −4.8 ± 17.3 mm Hg in the sham group: difference of −2.0 mm Hg (95% confidence interval [CI]: −5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was −1.1 (95% CI: −4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was −3.3 (95 CI: −6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the Denervation group and 15.0% in the sham group (95% CI: −3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was −1.4 ± 7.4 in the Denervation group and −1.3 ± 7.3 in the sham group; (95% CI: −1.5 to 1.4; p = 0.94). Conclusions This trial did not demonstrate a benefit of renal artery Denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261 )