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Han JH, Sharapatov Y, Do MT, Kim SY, Han B, Choi EK, Jeong CW. Safety and efficacy of extravascular renal denervation using HyperQure™ renal denervation system in short-term swine model of hypertension. Clin Exp Hypertens 2025; 47:2474520. [PMID: 40040356 DOI: 10.1080/10641963.2025.2474520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 02/24/2025] [Accepted: 02/26/2025] [Indexed: 03/06/2025]
Abstract
This study investigated the safety and efficacy of the HyperQure™ extravascular renal denervation (RDN) system in a swine model of mild hypertension. Ten female pigs were fed a 3% salt diet to induce hypertension and underwent either extravascular RDN using the HyperQure™ RDN system (n = 7) or a sham procedure (n = 3). Blood pressure (BP) was continuously monitored using implanted transmitters, and safety assessments were conducted via computed tomography angiography (CTA) at 28 days post-procedure. The primary endpoint was the change in systolic blood pressure (SBP) at four weeks, while secondary endpoints included changes in diastolic BP (DBP), mean arterial pressure (MAP), and histological evaluation of renal nerve and artery integrity. At four weeks, SBP decreased by 11.8 ± 5.2 mmHg in the RDN group compared to an increase of 6.4 ± 4.2 mmHg in controls, resulting in a mean difference of 18.2 mmHg (p < .05). Similar improvements were observed in DBP and MAP, with mean differences of 15.4 and 16.2 mmHg, respectively (both p < .05). CTA revealed no significant renal artery or intraperitoneal organ injury. Histological analysis confirmed effective nerve ablation, as evidenced by reduced tyrosine hydroxylase staining, without intimal damage. No postoperative complications were observed during the 28-day study period. These findings demonstrate the safety and efficacy of the HyperQure™ extravascular RDN system in reducing BP, providing a promising alternative for patients with resistant hypertension or those ineligible for intravascular RDN. Further clinical trials are warranted to validate these results.
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Affiliation(s)
- Jang Hee Han
- Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Yerzhan Sharapatov
- Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Department of Urology, Astana Medical University, Astana, Kazakhstan
| | - Minh-Tung Do
- Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Sang Youn Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Bogyeong Han
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Department of Pathology, Samsung Medical Center, Seoul, South Korea
| | - Eue-Keun Choi
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Chang Wook Jeong
- Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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Jiang H, Kittipibul V, Mahfoud F, Böhm M, Sobotka PA, Esler M, Wang J, Fudim M. The road to renal denervation for hypertension and beyond (HF): two decades of failed, succeeded, and to be determined. Heart Fail Rev 2025; 30:293-314. [PMID: 39509056 DOI: 10.1007/s10741-024-10463-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2024] [Indexed: 11/15/2024]
Abstract
Activation of the sympathetic nervous system has been attributed to the development of hypertension. Two established approaches for treating hypertension are pharmacotherapy and lifestyle changes. With an improved understanding of renal nerve anatomy and physiology, renal denervation has been proposed as an alternative treatment for hypertension. Specifically, it has been shown that the interruption of sympathetic nerves connecting the kidney and the sympathetic nervous system can reduce blood pressure. Here, we present a review on how renal denervation can help hypertension patients, specifically focusing on our novel understanding of renal nerve anatomy, denervation technique, and subsequent clinical trials, and how it may be used to treat other cardiovascular diseases like heart failure.
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Affiliation(s)
- Haoran Jiang
- Duke University School of Medicine, Durham, NC, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Veraprapas Kittipibul
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Felix Mahfoud
- Department of Cardiology, University Heart Center, University Hospital Basel, Basel, Switzerland
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, Basel, Switzerland
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Michael Böhm
- Department of Internal Medicine III - Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Saarland University, Homburg, Germany
| | - Paul A Sobotka
- Department of Cardiology, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Murray Esler
- Baker IDI Heart and Diabetes Institute, Melbourne, Australia
| | - Jie Wang
- The First Affiliated Hospital With Nanjing Medical University, Nanjing, China
- Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, Columbia, NY, USA
| | - Marat Fudim
- Department of Medicine, Duke University Medical Center, Durham, NC, USA.
- Duke Clinical Research Institute, Durham, NC, USA.
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Abouelmagd AA, Hassanein ME, Shehata RIA, Kaoud OA, Hamouda H, Abbas OF, Gaballah M. Comparing the Efficacy of Renal Artery Denervation in Uncontrolled Hypertension: A Systematic Review and Network Meta-Analysis. Cureus 2024; 16:e70805. [PMID: 39493034 PMCID: PMC11531912 DOI: 10.7759/cureus.70805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 10/03/2024] [Indexed: 11/05/2024] Open
Abstract
The study aims to compare the outcomes of different renal denervation (RDN) procedures in the treatment of uncontrolled hypertension. We searched Scopus, PubMed, Web of Science, and Cochrane for RCTs evaluating different procedures of RDN for hypertension. The outcomes of this study were systolic blood pressure (SBP) daytime, diastolic blood pressure (DBP) daytime, SBP nighttime, DBP nighttime, SBP 24-hour, DBP 24-hour, SBP home, DBP home, SBP office, and DBP office. We did a frequentist network meta-analysis of 38 published RCTs evaluating the efficacy of different renal artery denervation procedures for uncontrolled hypertension compared to sham procedures or standardized stepped-care antihypertensive treatment (SSAHT). Radiofrequency (RF) alone showed a statistically significant reduction in DBP (24 hours), DBP (daytime), and DBP (nighttime): standardized mean difference (SMD): -2.01 (95% CI: (-3.34; -0.68)), SMD: -4.36 (95% CI: (-8.28; -0.44)), and SMD: -3.50 (95% CI: (-6.23; -0.76)), respectively, and showed a statistically significant reduction in SBP (24 hours), SBP (daytime), and SBP (nighttime): SMD: -3.93 (95% CI: (-6.01; -1.84)), SMD: -5.88 (95% CI: (-9.91; -1.85)), and SMD: -5.79 (95% CI: (-10.0; -1.58)), respectively. RF added to SSAHT has statistical significance in the reduction of DBP (nighttime), SBP (daytime), SBP (home), and SBP (nighttime) with a SMD of -7.63 (95% CI: (-14.21; -1.06)), SMD of -10.56 (95% CI: (-21.03; -0.08)), SMD of -23.20 (95% CI: (-36.72; -9.26)), and SMD of -14.03 (95% CI: (-25.43; -2.63)), respectively. We found that renal denervation, especially by RF, when added to SSAHT may be a promising therapeutic option for patients with treatment-resistant hypertension, particularly in cases where medication alone fails to achieve adequate blood pressure control.
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Affiliation(s)
- Alaa Abdrabou Abouelmagd
- Medicine, South Valley University, Qena, EGY
- Cardiology, Medical Research Group of Egypt, Negida Academy, Arlington, USA
| | | | | | | | - Heba Hamouda
- Medicine, Menoufiya University, Shibin Al Kawm, EGY
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Persu A, Stoenoiu MS, Maes F, Kreutz R, Mancia G, Kjeldsen SE. Late outcomes of renal denervation are more favourable than early ones: facts or fancies? Clin Kidney J 2023; 16:2357-2364. [PMID: 38046011 PMCID: PMC10689164 DOI: 10.1093/ckj/sfad231] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Indexed: 12/05/2023] Open
Abstract
Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.
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Affiliation(s)
- Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc Université Catholique de Louvain, Brussels, Belgium
- Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Maria S Stoenoiu
- Department of Internal Medicine, Rheumatology, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| | - Frédéric Maes
- Division of Cardiology, Cliniques Universitaires Saint-Luc Université Catholique de Louvain, Brussels, Belgium
- Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Reinhold Kreutz
- Charité – Universitätsmedizin Berlin, Institute of Clinical Pharmacology and Toxicology, Berlin, Germany
| | | | - Sverre E Kjeldsen
- Institute of Clinical Medicine, University of Oslo, Departments of Cardiology and Nephrology, Ullevaal Hospital, Oslo, Norway
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Reyes KRL, Rader F. Long-Term Safety and Antihypertensive Effects of Renal Denervation: Current Insights. Integr Blood Press Control 2023; 16:59-70. [PMID: 37701066 PMCID: PMC10494925 DOI: 10.2147/ibpc.s392410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/01/2023] [Indexed: 09/14/2023] Open
Abstract
Hypertension is the most potent modifiable risk factor for the development of cardiovascular morbidity and mortality worldwide. Nevertheless, blood pressure (BP) control on a broad scale appears to be insurmountable and has even worsened in the US. Barriers to sustained hypertension control are multifactorial and although lack of patient awareness and socioeconomic barriers to healthcare access may play a role, medication non-compliance and therapeutic inertia are major causes. Renal denervation (RDN) is a minimally invasive procedure that has been the subject of interest in clinical trials for more than a decade and although the first sham-controlled trial could not detect group difference between treated and untreated hypertensives, subsequent, better designed sham-controlled trials clearly demonstrated the BP lowering effect of RDN, as well as its safety. While to-date, RDN is not available for routine clinical practice, one major requirement for broad implementation is that the BP lowering effect is durable. Therefore, this review will summarize the available long-term data of the different RDN modalities with respect to both effectiveness and safety.
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Affiliation(s)
| | - Florian Rader
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Bhatt DL, Vaduganathan M, Kandzari DE, Leon MB, Rocha-Singh K, Townsend RR, Katzen BT, Oparil S, Brar S, DeBruin V, Fahy M, Bakris GL. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet 2022; 400:1405-1416. [PMID: 36130612 DOI: 10.1016/s0140-6736(22)01787-1] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/02/2022] [Accepted: 09/06/2022] [Indexed: 01/02/2023]
Abstract
BACKGROUND The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results. METHODS SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261. FINDINGS From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group. INTERPRETATION This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control. FUNDING Medtronic.
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Affiliation(s)
- Deepak L Bhatt
- Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
| | - Muthiah Vaduganathan
- Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA
| | | | - Martin B Leon
- New York Presbyterian Hospital, Columbia University Medical Center, and Cardiovascular Research Foundation, New York, NY, USA
| | | | - Raymond R Townsend
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Suzanne Oparil
- University of Alabama at Birmingham, Birmingham, AL, USA
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Guber K, Kirtane AJ. Renal Sympathetic Denervation for Hypertension. Kidney Int Rep 2022; 7:2129-2140. [PMID: 36217529 PMCID: PMC9546727 DOI: 10.1016/j.ekir.2022.06.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/16/2022] [Accepted: 06/27/2022] [Indexed: 12/01/2022] Open
Abstract
Arterial hypertension is the most prevalent global modifiable risk factor for cardiovascular morbidity and mortality. Despite the availability of numerous pharmacologic treatments, many patients do not achieve guideline-recommended blood pressure targets. Therefore, renal sympathetic denervation (RDN), a process in which catheter-directed techniques are used to ablate portions of the renal artery to reduce sympathetic activity, has been extensively investigated as a complementary and nonpharmacologic approach for the treatment of arterial hypertension. This review seeks to discuss the pathophysiological rationale of this strategy, to survey its history and development, and to highlight the current clinical evidence and possible future directions of its employment. In sum, RDN has demonstrated itself to be a safe and well-tolerated endovascular intervention that can reliably contribute to improved blood pressure control and, perhaps ultimately, significant cardiovascular prognosis.
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Affiliation(s)
- Kenneth Guber
- Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Ajay J. Kirtane
- Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, USA
- Cardiovascular Research Foundation, New York, New York, USA
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Nawar K, Mohammad A, Johns EJ, Abdulla MH. Renal denervation for atrial fibrillation: a comprehensive updated systematic review and meta-analysis. J Hum Hypertens 2022; 36:887-897. [PMID: 35094013 PMCID: PMC9553644 DOI: 10.1038/s41371-022-00658-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/17/2022] [Indexed: 01/31/2023]
Abstract
The study aims to compare clinical outcomes following renal denervation (RDN) in hypertensive patients with atrial fibrillation (AF). Three online databases were searched (MEDLINE, EMBASE and PubMed) for literature related to outcomes of RDN on hypertension and AF, between January 1, 2010, and June 1, 2021. Where possible, risk ratios (RR) and mean differences (MD) were combined using a random effects model. Significance was set at p ≤ 0.05. Seven trials were included that assessed the effect of adding RDN to pulmonary vein isolation (PVI) in patients with hypertension and AF. A total of 711 patients (329 undergoing PVI + RDN and 382 undergoing PVI alone), with an age range of 56 ± 6 to 68 ± 9 years, were included. Pooled analysis showed a significant lowering of AF recurrence in the PVI + RDN (31.3%) group compared to the PVI-only (52.9%) group (p < 0.00001). Pooled analysis of patients with resistant hypertension showed a significant mean reduction of systolic blood pressure (SBP) (-9.42 mm Hg, p = 0.05), but not diastolic blood pressure (DBP) (-4.11 mm Hg, p = 0.16) in favor of PVI + RDN. Additionally, the pooled analysis showed that PVI + RDN significantly improved estimated glomerular filtration rate (eGFR) (+10.2 mL/min per 1.73 m2, p < 0.001) compared to PVI alone. RDN procedures in these trials have proven to be both safe and efficacious with an overall complication rate of 6.32%. Combined PVI and RDN is beneficial for patients with hypertension and AF. Combined therapy showed improvement in SBP and eGFR, reducing the risk of AF recurrence. RDN may serve as an innovative intervention in the treatment of AF.
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Affiliation(s)
- Khaled Nawar
- School of Medicine, University College Cork, Cork, Ireland
| | - Ahmed Mohammad
- School of Medicine, University College Cork, Cork, Ireland
| | - Edward J Johns
- Department of Physiology, University College Cork, Cork, Ireland
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Rao A, Krishnan N. Update on Renal Sympathetic Denervation for the Treatment of Hypertension. Curr Cardiol Rep 2022; 24:1261-1271. [PMID: 35895182 DOI: 10.1007/s11886-022-01753-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/19/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Hypertension is a leading risk factor for all-cause mortality in adults; however, medication non-adherence and intolerance present an enormous treatment challenge. Given the critical role of renal sympathetic nerves in neurogenic control of blood pressure and pathophysiology of hypertension, renal sympathetic denervation (RDN) has been explored as a therapeutic strategy in hypertension treatment over the last 15 years. In this review, we will discuss the role of renal sympathetic nerves in the pathophysiology of hypertension, provide an update on the available evidence regarding the short- and long-term safety and effectiveness of RDN in the treatment of hypertension, and consider its future perspectives. RECENT FINDINGS RDN is a percutaneous endovascular catheter-based neuromodulation approach that enables ablation of renal sympathetic nerve fibers within the adventitial layer of the renal arteries using radiofrequency (most extensively studied), ultrasound energy, or neurolytics (e.g., alcohol). In the last decade, advancements in procedural techniques and well-designed sham-controlled trials utilizing 24-h ambulatory blood pressure measurements have demonstrated that RDN has an excellent safety profile and results in a modest reduction of blood pressure, in a wide range of hypertensive phenotypes (mild to resistant), irrespective of antihypertensive drug use and this effect is sustained over a 3-year period. Superiority of a particular RDN modality has not been yet established. Despite strong evidence demonstrating efficacy and safety of RDN, current data does not support its use as a primary approach in the treatment of hypertension due to its modest treatment effect and concerns around long-term sustainability. Perhaps the best utility of RDN is in hypertensives intolerant to antihypertensive medications or as an adjunct to aldosterone antagonists in the management of resistant hypertension. Patient selection will be critical to demonstrate a meaningful benefit of RDN. Future well-designed studies are necessary to determine predictors and measures of response to RDN, long-term efficacy given question of renal nerve regeneration, comparison of available technologies, safety in patients with advanced kidney disease, and improvement in patient quality of life measures.
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Affiliation(s)
- Arundati Rao
- Yale School of Medicine, Section of Nephrology, New Haven, CT, USA
| | - Namrata Krishnan
- Yale School of Medicine, Section of Nephrology, New Haven, CT, USA. .,Veterans Affairs Medical Center, Section of Nephrology, Dialysis unit, bldg 2, ground floor. 950 Campbell ave, West Haven, CT, 06516, USA.
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Abstract
Purpose of Review To update on definition, diagnosis, prevalence, patient characteristics, pathophysiology, and treatment of refractory hypertension (RfHTN). Recent Findings Refractory hypertension (RfHTN) is defined as blood pressure (BP) that is uncontrolled despite using ≥ 5 antihypertensive medications of different classes, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist (MRA) at maximal or maximally tolerated doses. This new phenotype is different from resistant hypertension (RHTN), defined as BP that is uncontrolled despite using ≥ 3 medications, commonly a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB]), and a diuretic. The RHTN phenotype includes controlled RHTN, BP that is controlled on 4 or more medications. RfHTN is largely attributable to increased sympathetic activity, unlike RHTN, which is mainly due to increased intravascular fluid volume frequently caused by hyperaldosteronism and chronic excessive sodium ingestion. Compared to those with controlled RHTN, patients with RfHTN have a higher prevalence of target organ damage and do not have elevated aldosterone levels. Ongoing clinical trials are assessing the safety and efficacy of using devices to aid with BP control in patients with RfHTN. Summary RfHTN is a separate entity from RHTN and is generally attributable to increased sympathetic activity.
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Pisano A, Iannone LF, Leo A, Russo E, Coppolino G, Bolignano D. Renal denervation for resistant hypertension. Cochrane Database Syst Rev 2021; 11:CD011499. [PMID: 34806762 PMCID: PMC8607757 DOI: 10.1002/14651858.cd011499.pub3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, in the last decade renal sympathetic ablation (renal denervation) has been proposed as a possible therapeutic alternative to treat this condition. OBJECTIVES We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile and kidney function, as well as the potential adverse events related to the procedure. SEARCH METHODS For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 3 November 2020: Cochrane Hypertension's Specialised Register, CENTRAL (2020, Issue 11), Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform (via CENTRAL) and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov were searched for ongoing trials. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed study risk of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). Certainty of evidence has been assessed using the GRADE approach. MAIN RESULTS We found 15 eligible studies (1416 participants). In four studies, renal denervation was compared to sham procedure; in the remaining studies, renal denervation was tested against standard or intensified antihypertensive therapy. Most studies had unclear or high risk of bias for allocation concealment and blinding. When compared to control, there was low-certainty evidence that renal denervation had little or no effect on the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (5 studies, 892 participants; RR 0.98, 95% CI 0.33 to 2.95), unstable angina (3 studies, 270 participants; RR 0.51, 95% CI 0.09 to 2.89) or hospitalisation (3 studies, 743 participants; RR 1.24, 95% CI 0.50 to 3.11). Based on moderate-certainty evidence, renal denervation may reduce 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (9 studies, 1045 participants; MD -5.29 mmHg, 95% CI -10.46 to -0.13), ABPM diastolic BP (8 studies, 1004 participants; MD -3.75 mmHg, 95% CI -7.10 to -0.39) and office diastolic BP (8 studies, 1049 participants; MD -4.61 mmHg, 95% CI -8.23 to -0.99). Conversely, this procedure had little or no effect on office systolic BP (10 studies, 1090 participants; MD -5.92 mmHg, 95% CI -12.94 to 1.10). Moderate-certainty evidence suggested that renal denervation may not reduce serum creatinine (5 studies, 721 participants, MD 0.03 mg/dL, 95% CI -0.06 to 0.13) and may not increase the estimated glomerular filtration rate (eGFR) or creatinine clearance (6 studies, 822 participants; MD -2.56 mL/min, 95% CI -7.53 to 2.42). AUTHORS' CONCLUSIONS: In patients with resistant hypertension, there is low-certainty evidence that renal denervation does not improve major cardiovascular outomes and renal function. Conversely, moderate-certainty evidence exists that it may improve 24h ABPM and diastolic office-measured BP. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardised procedural methods are necessary to clarify the utility of this procedure in this population.
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Affiliation(s)
- Anna Pisano
- Institute of Clinical Physiology, CNR - Italian National Council of Research, Reggio Calabria, Italy
| | | | - Antonio Leo
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Emilio Russo
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Giuseppe Coppolino
- Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Davide Bolignano
- Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy
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Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized, Blinded, Placebo-Controlled Trials. JACC Cardiovasc Interv 2021; 14:2614-2624. [PMID: 34743900 DOI: 10.1016/j.jcin.2021.09.020] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/09/2021] [Accepted: 09/14/2021] [Indexed: 11/20/2022]
Abstract
OBJECTIVES The authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications. BACKGROUND Renal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications. METHODS All blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use. RESULTS There were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference -3.61 mm Hg; 95% confidence interval [CI]: -4.89 to -2.33 mm Hg; P < 0.0001), ambulatory diastolic (-1.85 mm Hg; 95% CI: -2.78 to -0.92 mm Hg; P < 0.0001), office systolic (-5.86 mm Hg; 95% CI: -7.77 to -3.94 mm Hg; P < 0.0001), and office diastolic (-3.63 mm Hg; 95% CI: -4.77 to -2.50; P < 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (Pinteraction = NS for each comparison). CONCLUSIONS The randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2 mm Hg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.
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Aksenova AV, Sivakova OA, Blinova NV, Danilov NM, Elfimova EM, Kisliak OA, Litvin AY, Oshchepkova EV, Fomin VV, Chikhladze NM, Shelkova GV, Chazova IE. Russian Medical Society for Arterial Hypertension expert consensus. Resistant hypertension: detection and management. TERAPEVT ARKH 2021; 93:1018-1029. [DOI: 10.26442/00403660.2021.09.201007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 10/08/2021] [Indexed: 01/04/2023]
Abstract
The diagnosis of resistant arterial hypertension allows us to single out a separate group of patients in whom it is necessary to use special diagnostic methods and approaches to treatment. Elimination of reversible factors leading to the development of resistant arterial hypertension, such as non-adherence to therapy, inappropriate therapy, secondary forms of arterial hypertension, leads to an improvement in the patient's prognosis. Most patients with resistant hypertension should be evaluated to rule out primary aldosteronism, renal artery stenosis, chronic kidney disease, and obstructive sleep apnea. The algorithm for examining patients, recommendations for lifestyle changes and a step-by-step therapy plan can improve blood pressure control. It is optative to use the most simplified treatment regimen and long-acting combined drugs. For a separate category of patients, it is advisable to perform radiofrequency denervation of the renal arteries.
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Effect of Renal Denervation on Cardiac Function and Inflammatory Factors in Heart Failure After Myocardial Infarction. J Cardiovasc Pharmacol 2021; 76:602-609. [PMID: 32868626 PMCID: PMC7641177 DOI: 10.1097/fjc.0000000000000899] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Supplemental Digital Content is Available in the Text. Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.
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15
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Chepurnoĭ AG, Shugushev ZK, Maksimkin DA. [Second chance for renal artery denervation]. ANGIOLOGII︠A︡ I SOSUDISTAI︠A︡ KHIRURGII︠A︡ = ANGIOLOGY AND VASCULAR SURGERY 2021; 27:32-40. [PMID: 34166342 DOI: 10.33529/angio2021219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The article is a review of contemporary randomized studies on radiofrequency denervation of renal arteries, followed by critical assessment of their advantages and disadvantages for possible optimization of endovascular treatment of resistant arterial hypertension.
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Affiliation(s)
- A G Chepurnoĭ
- Cardiovascular Surgery Department, People's Friendship University of Russia, Moscow, Russia
| | - Z Kh Shugushev
- Cardiovascular Surgery Department, People's Friendship University of Russia, Moscow, Russia
| | - D A Maksimkin
- Cardiovascular Surgery Department, People's Friendship University of Russia, Moscow, Russia
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16
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Liang B, Liang Y, Li R, Gu N. Effect of renal denervation on long-term outcomes in patients with resistant hypertension. Cardiovasc Diabetol 2021; 20:117. [PMID: 34090434 PMCID: PMC8180124 DOI: 10.1186/s12933-021-01309-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 05/28/2021] [Indexed: 12/13/2022] Open
Abstract
Increasing studies strongly prove that renal denervation, a minimally invasive surgery, is a promising new non-drug treatment method that can effectively control blood pressure in patients with resistant hypertension, but the evaluation of the long-term blood pressure control effect of renal denervation for resistant hypertension is still lacking. Here, we critically review current long-term follow-up data about the use of renal denervation for RH to comprehensively evaluate the effectiveness of renal denervation for RH, and to provide practical guidance for practitioners who are establishing a renal denervation service. Limited by the current research, many problems need to be solved before renal denervation is applied to RH. In addition, ambulatory blood pressure should be the first choice for the evaluation of blood pressure. Finally, the continuous antihypertensive effect of renal denervation in different renal denervation systems also needs to be strictly compared.
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Affiliation(s)
- Bo Liang
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Liang
- Southwest Medical University, Luzhou, China
| | - Rui Li
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Ning Gu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
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17
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Abstract
PURPOSE OF REVIEW To review the data about the use of renal denervation (RDN), a minimally invasive surgery, for resistant hypertension (RH) and to provide practical guidance for practitioners who are establishing an RDN service. RECENT FINDINGS RDN can selectively ablate renal sympathetic nerve fibres, block the transmission of nerve impulses between central sympathetic nerve and kidney, to control blood pressure to as a novel promising non-drug treatment option for RH. At present, there are many researches on the treatment of RH by RDN, but there are some controversies. This review summarises and critically examines the evidence for RDN in the treatment of RH and identifies areas for future research. With the development of RDN, the continuous innovation of RDN technology and methods, the development about better evaluating the real-time success of RDN and the improvement for identifying individuals who are most likely to benefit from RDN will ultimately determine whether RDN represents a feasible way to manage RH in the future.
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Affiliation(s)
- Bo Liang
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yu-Xiu Zhao
- Hospital (T.C.M.) Affiliated to Southwest Medical University, Luzhou, China
| | - Ning Gu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
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18
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Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies. Animals (Basel) 2020; 10:ani10091446. [PMID: 32824935 PMCID: PMC7552649 DOI: 10.3390/ani10091446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/18/2020] [Indexed: 11/17/2022] Open
Abstract
New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.
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19
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Sobowale CO, Hori Y, Ajijola OA. Neuromodulation Therapy in Heart Failure: Combined Use of Drugs and Devices. J Innov Card Rhythm Manag 2020; 11:4151-4159. [PMID: 32724706 PMCID: PMC7377644 DOI: 10.19102/icrm.2020.110705] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 05/20/2020] [Indexed: 12/11/2022] Open
Abstract
Heart failure (HF) is the fastest-growing cardiovascular disease globally. The autonomic nervous system plays an important role in the regulation and homeostasis of cardiac function but, once there is HF, it takes on a detrimental role in cardiac function that makes it a rational target. In this review, we cover the remodeling of the autonomic nervous system in HF and the latest treatments available targeting it.
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Affiliation(s)
- Christopher O Sobowale
- UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Yuichi Hori
- UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.,Department of Cardiology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Olujimi A Ajijola
- UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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20
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Akinseye OA, Ralston WF, Johnson KC, Ketron LL, Womack CR, Ibebuogu UN. Renal Sympathetic Denervation: A Comprehensive Review. Curr Probl Cardiol 2020; 46:100598. [PMID: 32448758 DOI: 10.1016/j.cpcardiol.2020.100598] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 04/06/2020] [Indexed: 12/28/2022]
Abstract
In 2017, the American College of Cardiology and American Heart Association released its updated blood pressure guidelines, redefining hypertension to be any systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg. Among United States adults, these new parameters increased the prevalence of hypertension from 72.2 million (31.9%) to 103.3 million (45.6%) adults and decreased the rate of medication-controlled hypertension from 53.4% to 39% with the prevalence of resistant hypertension ranging from 12% to 18%. Results of the pivotal SPRINT trial showed that more intensive blood pressure control in diabetic patients decreased both cardiovascular events and all-cause mortality. However, even with ideal goals in mind, compliance remains an issue due to multiple causes, and approximately half of study participants had stopped taking their antihypertensive drug within a year. Renal sympathetic denervation is a process in which catheter-based techniques are used to ablate specific portions of the renal artery nerves with the goal of decreasing sympathetic nerve activity and reducing blood pressure. Several studies using renal artery denervation have already shown benefit in patients with resistant hypertension, and now newer trials are beginning to focus on those with stage II hypertension as an additional potential treatment population. This review will seek to summarize the current evidence surrounding renal artery denervation and discuss some of its future trials, current issues, and potential roles both in hypertension and other comorbidities.
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Yugar-Toledo JC, Moreno Júnior H, Gus M, Rosito GBA, Scala LCN, Muxfeldt ES, Alessi A, Brandão AA, Moreira Filho O, Feitosa ADDM, Passarelli Júnior O, Souza DDSMD, Amodeo C, Barroso WKS, Gomes MAM, Paiva AMGD, Barbosa ECD, Miranda RD, Vilela-Martin JF, Nadruz Júnior W, Rodrigues CIS, Drager LF, Bortolotto LA, Consolim-Colombo FM, Sousa MGD, Borelli FADO, Kaiser SE, Salles GF, Azevedo MDFD, Magalhães LBNC, Póvoa RMDS, Malachias MVB, Nogueira ADR, Jardim PCBV, Jardim TDSV. Brazilian Position Statement on Resistant Hypertension - 2020. Arq Bras Cardiol 2020; 114:576-596. [PMID: 32267335 PMCID: PMC7792719 DOI: 10.36660/abc.20200198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
| | - Heitor Moreno Júnior
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Campinas, SP - Brasil
| | - Miguel Gus
- Hospital Moinhos de Vento, Porto Alegre, RS - Brasil
| | | | | | - Elizabeth Silaid Muxfeldt
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ - Brasil
| | | | | | | | | | | | | | - Celso Amodeo
- Instituto Dante Pazzanese de Cardiologia,São Paulo, SP - Brasil
| | | | | | | | | | | | | | - Wilson Nadruz Júnior
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Campinas, SP - Brasil
| | - Cibele Isaac Saad Rodrigues
- Faculdade de Ciências Médicas e da Saúde Pontifícia Universidade Católica de são Paulo, São Paulo, SP - Brasil
| | - Luciano Ferreira Drager
- Instituto do Coração do Hospital das Clínicas da Faculdade Medicina Universidade de São Paulo,São Paulo, SP - Brasil
| | - Luiz Aparecido Bortolotto
- Instituto do Coração do Hospital das Clínicas da Faculdade Medicina Universidade de São Paulo,São Paulo, SP - Brasil
| | | | | | | | | | - Gil Fernando Salles
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ - Brasil
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22
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Bhatt DL, Majithia A. Continued Evolution of Renal Artery Denervation for Hypertension. JACC Cardiovasc Interv 2020; 13:485-487. [PMID: 32081242 DOI: 10.1016/j.jcin.2019.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 12/03/2019] [Indexed: 10/25/2022]
Affiliation(s)
- Deepak L Bhatt
- Brigham and Women's Hospital, Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
| | - Arjun Majithia
- Brigham and Women's Hospital, Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts
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Abstract
Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure levels on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for blood pressure lowering with baroreflex activation and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between baroreflex activation and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into blood pressure lowering with baroreflex activation and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.
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Affiliation(s)
- Thomas E Lohmeier
- From the Department of Physiology and Biophysics (T.E.L., J.E.H.), University of Mississippi Medical Center, Jackson
| | - John E Hall
- From the Department of Physiology and Biophysics (T.E.L., J.E.H.), University of Mississippi Medical Center, Jackson.,Mississippi Center for Obesity Research (J.E.H.), University of Mississippi Medical Center, Jackson
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Chen H, Ji M, Zhang Y, Xu Y, Qiao L, Shen L, Ge J. ReferencesEfficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial. Trials 2019; 20:653. [PMID: 31779672 PMCID: PMC6883652 DOI: 10.1186/s13063-019-3693-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 08/31/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Clinical data show that due to the limited effects of lifestyle regulation and unsatisfactory drug adherence, only half of the hypertensive population have their blood pressure (BP) under control. In recent years, catheter-based renal denervation (RDN) has been used as a novel approach for treating uncontrolled hypertension. The safety and efficacy of catheter-based RDN have been confirmed by a number of studies and trials in which the participants were all non-Chinese and RDN was conducted via radiofrequency or ultrasound. METHODS/DESIGN This study is a prospective multicenter randomized sham-controlled trial that aims to investigate the safety and efficacy of cryoablation RDN (cryo-RDN) using a novel dedicated cryoablation balloon catheter (Cryofocus, China). A total of 200 Chinese patients who have uncontrolled hypertension despite standard medical treatment will be enrolled. With drug standardization, eligible participants will be randomized in a 1:1 ratio to undergo cryo-RDN treatment or renal angiography alone as a sham treatment. The primary endpoint is defined as the change in 24-h ambulatory systolic blood pressure from baseline to 6 months. Office BP and other 24-h ambulatory BP are included as secondary endpoints. Safety endpoints primarily include any adverse effects. DISCUSSION This study was designed to verify the safety and efficacy of cryo-RDN with Cryofocus balloon catheters in uncontrolled hypertensive patients on polypharmacy. The aim is to provide a new way to improve the control of hypertension in China as a complement to drug therapy. TRIAL REGISTRATION ChiCTR, ChiCTR1800017707. Registered on 10 August 2018.
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Affiliation(s)
- Han Chen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Meng Ji
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Yi Zhang
- Department of Cardiology, Shanghai Tenth People’s Hospital, Shanghai, China
| | - Yawei Xu
- Department of Cardiology, Shanghai Tenth People’s Hospital, Shanghai, China
| | - Lingjuan Qiao
- CryoFocus MedTech (Shanghai) Co., Ltd., Shanghai, China
| | - Li Shen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Cardiovascular Diseases, Shanghai, China
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Cardiovascular Diseases, Shanghai, China
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Zhang WH, Zhou QN, Lu YM, Li YD, Zhang L, Zhang JH, Xing Q, Lv WK, Cheng XC, Zhang GG, Wang XS, Gu Q, Lou X, Guli B, Tang BP, Zhou XH. Renal Denervation Reduced Ventricular Arrhythmia After Myocardial Infarction by Inhibiting Sympathetic Activity and Remodeling. J Am Heart Assoc 2019; 7:e009938. [PMID: 30371294 PMCID: PMC6474949 DOI: 10.1161/jaha.118.009938] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Ventricular arrhythmia after myocardial infarction is the most important risk factor for sudden cardiac death, which poses a serious threat to human health. As the correlation between autonomic nervous systemic dysfunction and heart rhythm abnormality has been gradually revealed, remedies targeting autonomic nervous system dysfunction, especially the sympathetic nerve, have emerged. Among them, renal denervation is noted for its powerful effect on the inhibition of sympathetic nerve activity. We aim to investigate whether renal denervation can reduce ventricular arrhythmia after myocardial infarction and thus decrease the risk of sudden cardiac death. In addition, we explore the potential mechanism with respect to nerve activity and remodeling. Methods and Results Twenty-four beagles were randomized into the control (n=4), renal denervation (n=10), and sham (n=10) groups. Permanent left anterior descending artery ligation was performed to establish myocardial infarction in the latter 2 groups. Animals in the renal denervation group underwent both surgical and chemical renal denervation. Compared with dogs in the sham group, dogs in the renal denervation group demonstrated attenuated effective refractory period shortening and inhomogeneity, flattened restitution curve, increased ventricular threshold, and decreased ventricular arrhythmia. Heart rate variability assessment, catecholamine measurement, and nerve discharge recordings all indicated that renal denervation could reduce whole-body and local tissue sympathetic tone. Tissue analysis revealed a significant decrease in neural remodeling in both the heart and stellate ganglion. Conclusions Surgical and chemical renal denervation decreased whole-body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion. Consequently, renal denervation led to beneficial remodeling of the electrophysiological characteristics in the infarction border zone, translating to a decrease in ventricular arrhythmia after myocardial infarction.
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Affiliation(s)
- Wen-Hui Zhang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Qi-Na Zhou
- 2 Xinjiang Key Laboratory of Medical Animal Model Research Clinical Medical Research Institute The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Yan-Mei Lu
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Yao-Dong Li
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Ling Zhang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Jiang-Hua Zhang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Qiang Xing
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Wen-Kui Lv
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Xin-Chun Cheng
- 3 Geriatric Center The People's Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang China
| | - Ge-Ge Zhang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Xue-Sheng Wang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Qi Gu
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Xue Lou
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Buajier Guli
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Bao-Peng Tang
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
| | - Xian-Hui Zhou
- 1 Cardiac Pacing and Electrophysiological Division The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang China
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Carnagarin R, Lambert GW, Kiuchi MG, Nolde JM, Matthews VB, Eikelis N, Lambert EA, Schlaich MP. Effects of sympathetic modulation in metabolic disease. Ann N Y Acad Sci 2019; 1454:80-89. [DOI: 10.1111/nyas.14217] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 07/07/2019] [Accepted: 07/23/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Revathy Carnagarin
- Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit/Medical Research FoundationUniversity of Western Australia Perth Western Australia Australia
| | - Gavin W. Lambert
- Iverson Health Innovation Research InstituteSwinburne University of Technology Hawthorn Victoria Australia
- School of Health SciencesSwinburne University of Technology Hawthorn Victoria Australia
| | - Marcio G. Kiuchi
- Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit/Medical Research FoundationUniversity of Western Australia Perth Western Australia Australia
| | - Janis M. Nolde
- Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit/Medical Research FoundationUniversity of Western Australia Perth Western Australia Australia
| | - Vance B. Matthews
- Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit/Medical Research FoundationUniversity of Western Australia Perth Western Australia Australia
| | - Nina Eikelis
- Iverson Health Innovation Research InstituteSwinburne University of Technology Hawthorn Victoria Australia
- School of Health SciencesSwinburne University of Technology Hawthorn Victoria Australia
| | - Elisabeth A. Lambert
- Iverson Health Innovation Research InstituteSwinburne University of Technology Hawthorn Victoria Australia
- School of Health SciencesSwinburne University of Technology Hawthorn Victoria Australia
| | - Markus P. Schlaich
- Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit/Medical Research FoundationUniversity of Western Australia Perth Western Australia Australia
- Departments of Cardiology and NephrologyRoyal Perth Hospital Perth Western Australia Australia
- Neurovascular Hypertension and Kidney Disease LaboratoryBaker Heart and Diabetes Institute Melbourne Victoria Australia
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27
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Affiliation(s)
- Reetu R Singh
- From the Department of Physiology, Cardiovascular Disease Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
| | - Kate M Denton
- From the Department of Physiology, Cardiovascular Disease Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
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Catheter-based renal sympathetic denervation induces acute renal inflammation through activation of caspase-1 and NLRP3 inflammasome. Anatol J Cardiol 2019; 21:134-141. [PMID: 30821713 PMCID: PMC6457403 DOI: 10.14744/anatoljcardiol.2018.62257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objective: Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. Serum creatinine and estimated glomerular filtration rate have some limitations to predict the early stage of acute kidney injury (AKI). We investigated the changes of early inflammatory biomarkers in AKI following the RDN procedure. Methods: Twenty-five female swine were divided into three groups: normal control (Normal, n=5), sham-operated (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into three subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. Renal cortical tissue was harvested, and clinical parameters and inflammatory biomarkers were checked. Results: There were no significant changes in the clinical parameters between the normal control and sham-operated groups using contrast media. Inflammatory interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor-α, and anti-inflammatory IL-10 increased immediately and then decreased at week 2 after RDN in the renal cortical tissue. Leaderless protein, IL-1α level, increased at week 1 and then decreased at week 2 after RDN. Caspase-1 increased immediately after RDN until week 2. Apoptosis-associated speck-like protein containing a caspase recruitment domain and NLRP3 expressions increased immediately and then decreased at week 2 after RDN. Conclusion: The RDN could induce acute renal inflammation through the activation of caspase-1 and NLRP3 inflammasome.
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Renal Artery Denervation for Hypertension. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2019; 21:7. [PMID: 30762119 DOI: 10.1007/s11936-019-0715-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
PURPOSE OF REVIEW Hypertension (HTN) has a growing impact, already affecting over 1 billion people. An estimated 2-16% of those with HTN have resistant HTN. The sympathetic nervous system (SNS) is a recognized contributor to the pathophysiology of resistant HTN. Current hypertensive pharmacotherapy has not fully targeted the SNS; therefore, the SNS has become a prominent research therapeutic target. This review summarizes the evidence and rationale behind renal denervation (RDN) therapy and the technology available. RECENT FINDINGS Prior to the SYMPLICITY HTN-3 clinical trial, trials found RDN to be an effective procedure to control resistant hypertension. The failure of SYMPLICITY HTN-3 to meet its primary efficacy endpoint sparked further studies to address potential shortcomings. The subsequent SPYRAL program trials demonstrated efficacy of RDN therapy in a controlled manner; however, they were not adequately powered. Ongoing research is examining new, innovative RDN technology as well as defining appropriate patients to target for treatment. The data currently available for RDN in HTN and other states of SNS activation suffer from potential biases and limitations, highlighting the need for continued exploration. Contemporary studies are more promising and hypothesis-generating. Future trials and continued device innovation will be crucial for understanding the clinical applications of RDN therapy.
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Han W, Guan S, Gan Q, Zhai X, Wang M, Qu X. The safety of renal denervation as assessed by optical coherence tomography: pre- and post-procedure comparison with multi-electrode ablation catheter in animal experiment. Hellenic J Cardiol 2019; 61:190-196. [PMID: 30684647 DOI: 10.1016/j.hjc.2019.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 01/03/2019] [Accepted: 01/11/2019] [Indexed: 10/27/2022] Open
Abstract
OBJECTIVE To prove the effectiveness and safety of multi-electrode ablation catheter in renal denervation (RDN) by optical coherence tomography (OCT). METHODS Sixteen renal arteries were enrolled from 8 pigs. Angiography and OCT were performed to analyze the morphological changes before RDN and at 1-month follow-up. Blood pressure and creatinine were measured to prove the effectiveness and safety of the catheter. RESULTS One renal artery was excluded because of the small diameter. Fifteen renal arteries successfully underwent renal denervation and OCT. Mean blood pressure was significantly reduced at 1 month after RDN (122.40 ± 3.54 mmHg vs. 106.50 ± 2.06 mmHg, n = 8, P < .001). Creatinine follow-up after 1 month showed no significant change (45.37 ± 7.44 vs. 65.87 ± 49.20 μmol/L, n = 8, P = 0.275). The minimal lumen diameter showed that the renal artery immediately narrowed after the procedure (7.17 ± 0.60 mm vs. 5.93 ± 0.97 mm, n = 15, P < .001). Vasospasm, vascular wall edemas, and thrombus formations all showed significant changes after the procedure except renal artery dissection (0% vs. 21.4%, P = 0.067) under the OCT. Adverse event as renal artery occluded showed no significant difference (0% vs. 6.7%, P > .05). OCT results showed no significant difference in vasospasm, dissections, wall edemas, and thrombus formations (P > .05) at 1 month after the procedure. CONCLUSION This multi-electrode ablation catheter could cause minor injury to renal artery instantly after RDN, but it is found to be safe in the animal model at 1-month follow-up.
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Affiliation(s)
- Wenzheng Han
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Shaofeng Guan
- Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Qian Gan
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Xinrong Zhai
- Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Ming Wang
- Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Xinkai Qu
- Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
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Yu HT, Jeong DS, Pak HN, Park HS, Kim JY, Kim J, Lee JM, Kim KH, Yoon NS, Roh SY, Oh YS, Cho YJ, Shim J. 2018 Korean Guidelines for Catheter Ablation of Atrial Fibrillation: Part II. INTERNATIONAL JOURNAL OF ARRHYTHMIA 2018. [DOI: 10.18501/arrhythmia.2018.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Sakaoka A, Rousselle SD, Hagiwara H, Tellez A, Hubbard B, Sakakura K. Safety of catheter-based radiofrequency renal denervation on branch renal arteries in a porcine model. Catheter Cardiovasc Interv 2018; 93:494-502. [PMID: 30407718 PMCID: PMC6587466 DOI: 10.1002/ccd.27953] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 08/22/2018] [Accepted: 10/10/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVES We aimed to investigate the safety of radiofrequency (RF)-renal denervation (RDN) on branch renal arteries (RAs) in a porcine model. BACKGROUND The efficacy of RF-RDN was enhanced by treatment of the branch RA, in addition to the main RA. However, there are concerns regarding the safety of RF-RDN on branch RA because of their smaller diameter and proximity to the kidney. METHODS RF was delivered to 24 RA from 12 swine. A total of 8 RA from 4 swine were untreated. Treated RA were examined by angiography and histopathology at 7, 30, and 90 days. Serum creatinine concentration, biophysical parameters during RF delivery, and renal norepinephrine concentration were also assessed. RESULTS Angiography revealed minimal late lumen loss and diameter stenosis in the main and branch RA at any time point. There was no change in serum creatinine after RF-RDN. Histopathologically, no augmentation of medial damage or neointimal formation was found in branch RA compared with main RA. No or minimal damage to surrounding tissues including the kidneys, ureters, lymph nodes, and muscles was observed at any time point in both the main and branch RA. Equivalent electrode temperature in the main and branch RA was achieved by automatic adjustment of output power by the generator. The renal norepinephrine concentration was significantly lower in the treated group compared with the untreated group. CONCLUSIONS RF-RDN on branch RA was safe in a porcine model, with stenosis-free healing of treated arteries and negligible kidney damage at 7, 30, and 90 days.
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Affiliation(s)
- Atsushi Sakaoka
- Evaluation Center, R&D Administration and Promotion Department, Terumo Corporation, Kanagawa, Japan
| | | | - Hitomi Hagiwara
- Evaluation Center, R&D Administration and Promotion Department, Terumo Corporation, Kanagawa, Japan
| | - Armando Tellez
- Alizée Pathology, LLC, Thurmont, Maryland.,Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
| | | | - Kenichi Sakakura
- Division of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
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Warchol-Celinska E, Prejbisz A, Kadziela J, Florczak E, Januszewicz M, Michalowska I, Dobrowolski P, Kabat M, Sliwinski P, Klisiewicz A, Topor-Madry R, Narkiewicz K, Somers VK, Sobotka PA, Witkowski A, Januszewicz A. Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea. Hypertension 2018; 72:381-390. [PMID: 29941516 DOI: 10.1161/hypertensionaha.118.11180] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 04/18/2018] [Accepted: 04/29/2018] [Indexed: 12/31/2022]
Affiliation(s)
| | | | - Jacek Kadziela
- Department of Interventional Cardiology and Angiology (J.K., A.W.)
| | - Elzbieta Florczak
- From the Department of Hypertension (E.W.-C., A.P., E.F., M.K., A.J.)
| | - Magdalena Januszewicz
- Institute of Cardiology, Warsaw, Poland; Second Department of Radiology, Medical University of Warsaw, Poland (M.J.)
| | | | | | - Marek Kabat
- From the Department of Hypertension (E.W.-C., A.P., E.F., M.K., A.J.)
| | - Pawel Sliwinski
- Second Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland (P.S.)
| | - Anna Klisiewicz
- Department of Interventional Cardiology and Angiology (J.K., A.W.)
- Department of Congenital Heart Diseases (P.D., A.K.)
| | - Roman Topor-Madry
- Institute of Public Health, Jagiellonian University Medical College, Cracow, Poland (R.T.-M.)
| | - Krzysztof Narkiewicz
- Department of Hypertension and Diabetology, Medical University of Gdansk, Poland (K.N.)
| | - Virend K. Somers
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (V.K.S.)
| | - Paul A. Sobotka
- Department of Cardiovascular Diseases, Ohio State University, Columbus (P.A.S.)
- Rox Medical, Inc, San Clemente, CA (P.A.S.)
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Intravascular imaging, histopathological analysis, and catecholamine quantification following catheter-based renal denervation in a swine model: the impact of prebifurcation energy delivery. Hypertens Res 2018; 41:708-717. [PMID: 30006641 DOI: 10.1038/s41440-018-0072-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 01/26/2018] [Accepted: 02/02/2018] [Indexed: 12/16/2022]
Abstract
The purpose of this study was to evaluate the impact of prebifurcation renal denervation in a swine model and assess its safety through optical coherence tomography (OCT). Prebifurcation renal denervation with a multi-electrode catheter was performed in one renal artery of 12 healthy pigs, with the contralateral artery and kidney being used as controls. Angiograms and OCT pullbacks were obtained peri-procedurally and 1 month post procedure. Renal tissue catecholamines were quantified, and the arterial wall and peri-adventitial tissue were analyzed histologically. Intraluminal changes (endothelial swelling, spasm, and thrombus formation) were observed acutely by OCT in most of the treated arteries and were no longer visible at follow-up. Histology revealed a statistically significant accumulation of collagen (fibrosis) and a near absence of tyrosine hydroxylase labeling in the denervated artery, suggesting a clear reduction in nervous terminals. Renal tissue catecholamine levels were similar between both sides, probably due to the low number of ablation points and the renorenal reflex. The present study demonstrates that renal denervation is associated with acute intimal disruptions, areas of fibrosis, and a reduction in nervous terminals. The lack of difference in renal tissue catecholamine levels is indicative of the need to perform the highest and safest number of ablation points in both renal arteries. These findings are important because they demonstrate the histological consequences of radiofrequency energy application and its medium-term safety.
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35
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Pappaccogli M, Covella M, Berra E, Fulcheri C, Di Monaco S, Perlo E, Burrello J, Monticone S, Rossato D, Rabbia F, Veglio F. Effectiveness of Renal Denervation in Resistant Hypertension: A Meta-Analysis of 11 Controlled Studies. High Blood Press Cardiovasc Prev 2018; 25:167-176. [DOI: 10.1007/s40292-018-0260-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 04/27/2018] [Indexed: 10/16/2022] Open
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36
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Solomonica A, Lavi S, Choudhury T, Bagur R. Renal denervation therapy beyond resistant hypertension. J Thorac Dis 2018; 10:707-713. [PMID: 29607139 DOI: 10.21037/jtd.2018.01.87] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Amir Solomonica
- London Health Sciences Centre, Western University, London, Ontario, Canada
| | - Shahar Lavi
- London Health Sciences Centre, Western University, London, Ontario, Canada
| | - Tawfiq Choudhury
- London Health Sciences Centre, Western University, London, Ontario, Canada
| | - Rodrigo Bagur
- London Health Sciences Centre, Western University, London, Ontario, Canada.,Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute of Primary Care and Health Sciences, University of Keele, Stoke-on-Trent, UK
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37
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Mauriello A, Rovella V, Borri F, Anemona L, Giannini E, Giacobbi E, Saggini A, Palmieri G, Anselmo A, Bove P, Melino G, Valentina G, Tesauro M, Gabriele D, Di Daniele N. Hypertension in kidney transplantation is associated with an early renal nerve sprouting. Nephrol Dial Transplant 2018; 32:1053-1060. [PMID: 28498963 PMCID: PMC5837349 DOI: 10.1093/ndt/gfx069] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 02/20/2017] [Indexed: 12/30/2022] Open
Abstract
Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation.
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Affiliation(s)
- Alessandro Mauriello
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Valentina Rovella
- Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Filippo Borri
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Lucia Anemona
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Elena Giannini
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Erica Giacobbi
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Andrea Saggini
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Giampiero Palmieri
- Anatomic Pathology, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - Alessandro Anselmo
- Transplantation Surgery, Department of Surgery Policlinico Tor Vergata Foundation, Rome, Italy
| | - Pierluigi Bove
- Urology, Department of Experimental Medicine and Surgery, Rome, Italy
| | - Gerry Melino
- Biochemistry, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Guardini Valentina
- Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Manfredi Tesauro
- Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - D'Urso Gabriele
- Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Nicola Di Daniele
- Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
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Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Cosedis Nielsen J, Curtis AB, Davies DW, Day JD, d’Avila A, (Natasja) de Groot NMS, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace 2018; 20:e1-e160. [PMID: 29016840 PMCID: PMC5834122 DOI: 10.1093/europace/eux274] [Citation(s) in RCA: 787] [Impact Index Per Article: 112.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Hugh Calkins
- From the Johns Hopkins Medical Institutions, Baltimore, MD
| | | | - Riccardo Cappato
- Humanitas Research Hospital, Arrhythmias and Electrophysiology Research Center, Milan, Italy (Dr. Cappato is now with the Department of Biomedical Sciences, Humanitas University, Milan, Italy, and IRCCS, Humanitas Clinical and Research Center, Milan, Italy)
| | | | - Eduardo B Saad
- Hospital Pro-Cardiaco and Hospital Samaritano, Botafogo, Rio de Janeiro, Brazil
| | | | | | - Vinay Badhwar
- West Virginia University School of Medicine, Morgantown, WV
| | - Josep Brugada
- Cardiovascular Institute, Hospital Clínic, University of Barcelona, Catalonia, Spain
| | - John Camm
- St. George's University of London, London, United Kingdom
| | | | | | | | | | | | - D Wyn Davies
- Imperial College Healthcare NHS Trust, London, United Kingdom
| | - John D Day
- Intermountain Medical Center Heart Institute, Salt Lake City, UT
| | | | | | - Luigi Di Biase
- Albert Einstein College of Medicine, Montefiore-Einstein Center for Heart & Vascular Care, Bronx, NY
| | | | | | | | | | - Sabine Ernst
- Royal Brompton and Harefield NHS Foundation Trust, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Guilherme Fenelon
- Albert Einstein Jewish Hospital, Federal University of São Paulo, São Paulo, Brazil
| | | | | | | | | | - Elaine Hylek
- Boston University School of Medicine, Boston, MA
| | - Warren M Jackman
- Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Jose Jalife
- University of Michigan, Ann Arbor, MI, the National Center for Cardiovascular Research Carlos III (CNIC) and CIBERCV, Madrid, Spain
| | - Jonathan M Kalman
- Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
| | - Josef Kautzner
- Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Hans Kottkamp
- Hirslanden Hospital, Department of Electrophysiology, Zurich, Switzerland
| | | | | | - Richard Lee
- Saint Louis University Medical School, St. Louis, MO
| | - Thorsten Lewalter
- Department of Cardiology and Intensive Care, Hospital Munich-Thalkirchen, Munich, Germany
| | | | - Laurent Macle
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, Canada
| | | | - Francis E Marchlinski
- Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA
| | | | - Hiroshi Nakagawa
- Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Andrea Natale
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, TX
| | - Stanley Nattel
- Montreal Heart Institute and Université de Montréal, Montreal, Canada, McGill University, Montreal, Canada, and University Duisburg-Essen, Essen, Germany
| | - Ken Okumura
- Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | | | - Evgeny Pokushalov
- State Research Institute of Circulation Pathology, Novosibirsk, Russia
| | | | - Prashanthan Sanders
- Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
| | | | | | - Claudio Tondo
- Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino, IRCCS, Department of Cardiovascular Sciences, University of Milan, Milan, Italy
| | | | - Atul Verma
- Southlake Regional Health Centre, University of Toronto, Toronto, Canada
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Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Nielsen JC, Curtis AB, Davies DW, Day JD, d’Avila A, de Groot N(N, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017; 14:e275-e444. [PMID: 28506916 PMCID: PMC6019327 DOI: 10.1016/j.hrthm.2017.05.012] [Citation(s) in RCA: 1513] [Impact Index Per Article: 189.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Hugh Calkins
- Johns Hopkins Medical Institutions, Baltimore, MD
| | | | - Riccardo Cappato
- Humanitas Research Hospital, Arrhythmias and Electrophysiology Research Center, Milan, Italy (Dr. Cappato is now with the Department of Biomedical Sciences, Humanitas University, Milan, Italy, and IRCCS, Humanitas Clinical and Research Center, Milan, Italy)
| | | | - Eduardo B. Saad
- Hospital Pro-Cardiaco and Hospital Samaritano, Botafogo, Rio de Janeiro, Brazil
| | | | | | - Vinay Badhwar
- West Virginia University School of Medicine, Morgantown, WV
| | - Josep Brugada
- Cardiovascular Institute, Hospital Clínic, University of Barcelona, Catalonia, Spain
| | - John Camm
- St. George’s University of London, London, United Kingdom
| | | | | | | | | | | | - D. Wyn Davies
- Imperial College Healthcare NHS Trust, London, United Kingdom
| | - John D. Day
- Intermountain Medical Center Heart Institute, Salt Lake City, UT
| | | | | | - Luigi Di Biase
- Albert Einstein College of Medicine, Montefiore-Einstein Center for Heart & Vascular Care, Bronx, NY
| | | | | | | | | | - Sabine Ernst
- Royal Brompton and Harefield NHS Foundation Trust, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Guilherme Fenelon
- Albert Einstein Jewish Hospital, Federal University of São Paulo, São Paulo, Brazil
| | | | | | | | | | - Elaine Hylek
- Boston University School of Medicine, Boston, MA
| | - Warren M. Jackman
- Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Jose Jalife
- University of Michigan, Ann Arbor, MI, the National Center for Cardiovascular Research Carlos III (CNIC) and CIBERCV, Madrid, Spain
| | - Jonathan M. Kalman
- Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
| | - Josef Kautzner
- Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Hans Kottkamp
- Hirslanden Hospital, Department of Electrophysiology, Zurich, Switzerland
| | | | | | - Richard Lee
- Saint Louis University Medical School, St. Louis, MO
| | - Thorsten Lewalter
- Department of Cardiology and Intensive Care, Hospital Munich-Thalkirchen, Munich, Germany
| | | | - Laurent Macle
- Montreal Heart Institute, Department of Medicine, Université de Montréal, Montréal, Canada
| | | | - Francis E. Marchlinski
- Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA
| | | | - Hiroshi Nakagawa
- Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Andrea Natale
- Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, Austin, TX
| | - Stanley Nattel
- Montreal Heart Institute and Université de Montréal, Montreal, Canada, McGill University, Montreal, Canada, and University Duisburg-Essen, Essen, Germany
| | - Ken Okumura
- Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | | | - Evgeny Pokushalov
- State Research Institute of Circulation Pathology, Novosibirsk, Russia
| | | | - Prashanthan Sanders
- Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
| | | | | | - Claudio Tondo
- Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino, IRCCS, Department of Cardiovascular Sciences, University of Milan, Milan, Italy
| | | | - Atul Verma
- Southlake Regional Health Centre, University of Toronto, Toronto, Canada
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Waksman R, Bakris GL, Steinvil A, Garcia-Garcia H, Brown AL, DiFilippo W, Scott T, Singh J, DeBruin V, Jones D, Jolivette D, Bhatt DL. High screen failure rate in patients with resistant hypertension: Findings from SYMPLICITY HTN-3. Am Heart J 2017; 192:76-84. [PMID: 28938966 DOI: 10.1016/j.ahj.2017.06.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 06/22/2017] [Indexed: 11/24/2022]
Abstract
BACKGROUND The SYMPLICITY HTN-3 trial, which randomized subjects to renal denervation (RDN) or sham control, was designed to evaluate the efficacy and safety of RDN for the treatment of resistant hypertension. Outcomes were previously reported. This retrospective analysis evaluated reasons for screen failure (SF) for randomization in the trial. METHODS SYMPLICITY HTN-3 enrolled subjects with office systolic blood pressure (SBP) ≥160 mmHg on stable and maximal doses of ≥3 antihypertensive medication classes. Blood pressure was measured during screening visit (SV) 1 and SV2 a minimum of 2 weeks later to ensure resistant hypertension and to exclude white-coat hypertension. We analyzed baseline characteristics and reasons for SF at each SV and changes in BP between SVs. RESULTS Among 1,415 patients screened, 880 (62%) did not meet criteria for randomization. Compared with randomized patients, those in the SF cohort were more likely to be older (58.7 vs. 57.4 years, P=.029), current smokers (14.5% vs. 10.7%, P=.041), and prescribed fewer antihypertensive medications (4.7 vs. 5.1, P<.001). The predominant reason for SF at SV2 was office SBP <160 mmHg despite office SBP ≥160 mmHg at SV1. CONCLUSION Screening patients with resistant hypertension on maximal doses of ≥3 antihypertensive drugs led to a high SF rate. Screen failures were most common at SV1 and were due to failing the office SBP entry criteria. Not meeting ambulatory SBP criteria at SV2 was a secondary reason for SF, often due to white-coat hypertension; thus, 24-hour ambulatory monitoring is important to validate resistant hypertension.
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WITHDRAWN: 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. J Arrhythm 2017. [DOI: 10.1016/j.joa.2017.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Chen XH, Kim S, Zeng XX, Chen ZB, Cui TL, Hu ZX, Li Y, Fu P. Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis. Chin Med J (Engl) 2017. [PMID: 28639575 PMCID: PMC5494923 DOI: 10.4103/0366-6999.208238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.
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Affiliation(s)
- Xiao-Han Chen
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Sehee Kim
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA
| | - Xiao-Xi Zeng
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University; West China Biostatistics and Cost-benefit Analysis Center of Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhi-Bing Chen
- Department of Burn and Plastic Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan 610017, China
| | - Tian-Lei Cui
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhang-Xue Hu
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yi Li
- Department of Biostatistics, University of Michigan School of Public Health; Kidney Epidemiology and Cost Center, University of Michigan, Ann Arbor, Michigan 48109, USA
| | - Ping Fu
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University; West China Biostatistics and Cost-benefit Analysis Center of Sichuan University, Chengdu, Sichuan 610041, China
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Affiliation(s)
- Hillel Sternlicht
- From the Section of Nephrology and Hypertension, Department of Medicine, Lenox Hill Hospital, New York, NY; and ASH Comprehensive Hypertension Center, Department of Medicine, The University of Chicago Medicine, IL
| | - George L. Bakris
- From the Section of Nephrology and Hypertension, Department of Medicine, Lenox Hill Hospital, New York, NY; and ASH Comprehensive Hypertension Center, Department of Medicine, The University of Chicago Medicine, IL
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Chen S, Kiuchi MG, Acou WJ, Derndorfer M, Wang J, Li R, Kollias G, Martinek M, Kiuchi T, Pürerfellner H, Liu S. Feasibility of catheter ablation renal denervation in “mild” resistant hypertension. J Clin Hypertens (Greenwich) 2017; 19:361-368. [DOI: 10.1111/jch.12988] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Revised: 11/08/2016] [Accepted: 11/11/2016] [Indexed: 11/29/2022]
Affiliation(s)
- Shaojie Chen
- Evidence-Based Medicine; Department of Cardiology; Shanghai General Hospital; Shanghai First People's Hospital; Shanghai Jiao Tong University School of Medicine; Shanghai China
- Collaborative Postdoc Program Project on Renal Denervation (CPPP-RDN); Pacemed; Rio de Janeiro Brazil
- Fellowship EHRA/ESC; Academic Teaching Center; Department of Cardiology; Allgemein öffentliches Krankenhaus Elisabethinen Linz / Elisabethinen University Teaching Hospital of Medical University Innsbruck and Vienna; Linz Oberösterreich Austria
| | - Marcio Galindo Kiuchi
- Collaborative Postdoc Program Project on Renal Denervation (CPPP-RDN); Pacemed; Rio de Janeiro Brazil
- Cardiac Surgery and Artificial Cardiac Stimulation Division; Department of Medicine; Hospital e Clínica São Gonçalo; Rio de Janeiro Brazil
- Department of Medicine; Universidade Federal Fluminense; Rio de Janeiro Brazil
| | | | - Michael Derndorfer
- Department of Cardiology; Allgemein öffentliches Krankenhaus Elisabethinen Linz / Elisabethinen University Teaching Hospital of Medical University Innsbruck and Vienna; Linz Oberösterreich Austria
| | - Jiazhi Wang
- Humanmedzin; Universität Leipzig; Leipzig Germany
| | - Ruotian Li
- Abteilung der Kardiologie; Herzzentrum Leipzig; Leipzig Germany
| | - Georgios Kollias
- Department of Cardiology; Allgemein öffentliches Krankenhaus Elisabethinen Linz / Elisabethinen University Teaching Hospital of Medical University Innsbruck and Vienna; Linz Oberösterreich Austria
| | - Martin Martinek
- Department of Cardiology; Allgemein öffentliches Krankenhaus Elisabethinen Linz / Elisabethinen University Teaching Hospital of Medical University Innsbruck and Vienna; Linz Oberösterreich Austria
| | | | - Helmut Pürerfellner
- Department of Cardiology; Allgemein öffentliches Krankenhaus Elisabethinen Linz / Elisabethinen University Teaching Hospital of Medical University Innsbruck and Vienna; Linz Oberösterreich Austria
| | - Shaowen Liu
- Department of Cardiology; Shanghai General Hospital / Shanghai First People's Hospital; Shanghai Jiao Tong University School of Medicine; Shanghai China
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Affiliation(s)
- Prashant D Bhave
- Divison of Cardiology, Wake Forest University Health Sciences Center, Winston-Salem, NC
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Coppolino G, Pisano A, Rivoli L, Bolignano D, Cochrane Hypertension Group. Renal denervation for resistant hypertension. Cochrane Database Syst Rev 2017; 2:CD011499. [PMID: 28220472 PMCID: PMC6464209 DOI: 10.1002/14651858.cd011499.pub2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications, or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, renal sympathetic ablation (renal denervation) has been recently proposed as a possible therapeutic alternative to treat this condition. OBJECTIVES We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile, and kidney function, as well as the potential adverse events related to the procedure. SEARCH METHODS We searched the following databases to 17 February 2016 using relevant search terms: the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed study risks of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). MAIN RESULTS We found 12 eligible studies (1149 participants). In four studies, renal denervation was compared to sham procedure; one study compared a proximal ablation to a complete renal artery denervation; in the remaining, renal denervation was tested against standard or intensified antihypertensive therapy.None of the included trials was designed to look at hard clinical end points as primary outcomes.When compared to control, there was low quality evidence that renal denervation did not reduce the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (4 studies, 823 participants; RR 1.15, 95% CI 0.36 to 3.72), or unstable angina (2 studies, 201 participants; RR 0.63, 95% CI 0.08 to 5.06), and moderate quality evidence that it had no effect on 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (5 studies, 797 participants; MD 0.28 mmHg, 95% CI -3.74 to 4.29), diastolic BP (4 studies, 756 participants; MD 0.93 mmHg, 95% CI -4.50 to 6.36), office measured systolic BP (6 studies, 886 participants; MD -4.08 mmHg, 95% CI -15.26 to 7.11), or diastolic BP (5 studies, 845 participants; MD -1.30 mmHg, 95% CI -7.30 to 4.69). Furthermore, low quality evidence suggested that this procedure produced no effect on either serum creatinine (3 studies, 736 participants, MD 0.01 mg/dL; 95% CI -0.12 to 0.14), estimated glomerular filtration rate (eGFR), or creatinine clearance (4 studies, 837 participants; MD -2.09 mL/min, 95% CI -8.12 to 3.95). Based on low-quality evidence, renal denervation significantly increased bradycardia episodes compared to control (3 studies, 220 participants; RR 6.63, 95% CI 1.19 to 36.84), while the risk of other adverse events was comparable or not assessable.Data were sparse or absent for all cause mortality, hospitalisation, fatal cardiovascular events, quality of life, atrial fibrillation episodes, left ventricular hypertrophy, sleep apnoea severity, need for renal replacement therapy, and metabolic profile.The quality of the evidence was low for cardiovascular outcomes and adverse events and moderate for lack of effect on blood pressure and renal function. AUTHORS' CONCLUSIONS In patients with resistant hypertension, there is low quality evidence that renal denervation does not change major cardiovascular events, and renal function. There was moderate quality evidence that it does not change blood pressure and and low quality evidence that it caused an increaseof bradycardia episodes. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardized procedural methods are necessary to clarify the utility of this procedure in this population.
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Affiliation(s)
- Giuseppe Coppolino
- "Pugliese‐Ciaccio" General HospitalNephrology and Dialysis UnitViale pio XCatanzaroCatanzaroItaly88100
| | - Anna Pisano
- CNR ‐ Italian National Council of ResearchInstitute of Clinical PhysiologyCNR‐IFC Via Vallone Petrara c/o Ospedali RiunitiReggio CalabriaItaly89100
| | - Laura Rivoli
- University "Magna Graecia"Department of Medical and Surgical Sciences, Nephrology and Dialysis UnitViale EuropaCatanzaroItaly88100
| | - Davide Bolignano
- CNR ‐ Italian National Council of ResearchInstitute of Clinical PhysiologyCNR‐IFC Via Vallone Petrara c/o Ospedali RiunitiReggio CalabriaItaly89100
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Bohlender JM, Nussberger J, Birkhäuser F, Grouzmann E, Thalmann GN, Imboden H. Resetting of renal tissular renin-angiotensin and bradykinin-kallikrein systems after unilateral kidney denervation in rats. Histochem Cell Biol 2017; 147:585-593. [PMID: 28220244 DOI: 10.1007/s00418-017-1543-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2017] [Indexed: 01/11/2023]
Abstract
The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems in rats 6 days after left kidney denervation (DNX, n = 8) compared to sham-operated controls (CTR, n = 8). Plasma renin concentration was unchanged in DNX vs. CTR (p = NS). Kidney bradykinin (BK) and angiotensin (Ang) I and II concentrations decreased bilaterally in DNX vs. CTR rats (~20 to 40%, p < 0.05) together with Ang IV and V concentrations that were extremely low (p = NS). Renin, Ang III and dopamine concentrations decreased by ~25 to 50% and norepinephrine concentrations by 99% in DNX kidneys (p < 0.05) but were unaltered in opposite kidneys. Ang II/I and KA were comparable in DNX, contralateral and CTR kidneys. Ang III/II increased in right vs. DNX or CTR kidneys (40-50%, p < 0.05). Ang II was mainly located in tubular epithelium by immunocytological staining and its cellular distribution was unaffected by DNX. Moreover, the angiotensinergic and catecholaminergic innervation of right kidneys was unchanged vs. CTR. We found an important dependency of tissular Ang and BK levels on the renal innervation that may contribute to the resetting of kidney function after DNX. The DNX-induced peptide changes were not readily explained by kidney KA, renin or plasma Ang I generation. However, tissular peptide metabolism and compartmentalization may have played a central role. The mechanisms behind the concentration changes remain unclear and deserve further clarification.
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Affiliation(s)
- Jürgen M Bohlender
- Institute for Cell Biology, University of Bern, Bern, Switzerland. .,Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 4, 3010, Bern, Switzerland.
| | - Jürg Nussberger
- Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Frédéric Birkhäuser
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Eric Grouzmann
- Service of Biomedicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - George N Thalmann
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Hans Imboden
- Institute for Cell Biology, University of Bern, Bern, Switzerland
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Denker MG, Cohen DL. Resistant Hypertension and Renal Nerve Denervation. Methodist Debakey Cardiovasc J 2016; 11:240-4. [PMID: 27057294 DOI: 10.14797/mdcj-11-4-240] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Patients with resistant hypertension are a subgroup of the hypertensive population that are at even greater risk of cardiovascular outcomes. Therapeutic options for these patients are limited to antihypertensive medications. However, renal denervation (RDN) is a novel nonpharmacologic intervention that involves a catheter-based ablation of the sympathetic nerves within the renal artery wall. The procedure initially showed promise with remarkable blood pressure reductions until the pivotal SYMPLICITY HTN-3 trial failed to demonstrate superiority of RDN over control. This trial was notable for a substantial placebo effect and an attenuated response to RDN. These findings, which contradicted those of prior studies, have raised numerous questions, including whether adequate RDN occurred in those patients. Further research is planned to resolve some of these questions and to clarify the role of RDN in treating patients with resistant hypertension.
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Affiliation(s)
- Matthew G Denker
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Debbie L Cohen
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
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Regression to the Mean in SYMPLICITY HTN-3. J Am Coll Cardiol 2016; 68:2016-2025. [DOI: 10.1016/j.jacc.2016.07.775] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Revised: 06/25/2016] [Accepted: 07/20/2016] [Indexed: 11/23/2022]
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Rosa J, Zelinka T, Petrák O, Štrauch B, Holaj R, Widimský J. Should All Patients with Resistant Hypertension Receive Spironolactone? Curr Hypertens Rep 2016; 18:81. [PMID: 27787836 DOI: 10.1007/s11906-016-0690-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Ján Rosa
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
- Cardiocenter, University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Tomáš Zelinka
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Ondřej Petrák
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Branislav Štrauch
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Robert Holaj
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jiří Widimský
- 3rd Department of Medicine, Center for Hypertension, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
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