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Yang X, Lin L, Zhang Z, Chen X. Effects of catheter-based renal denervation on renin-aldosterone system, catecholamines, and electrolytes: A systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2022; 24:1537-1546. [PMID: 36321724 PMCID: PMC9731592 DOI: 10.1111/jch.14590] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/26/2022] [Accepted: 10/03/2022] [Indexed: 11/07/2022]
Abstract
In recent years, catheter-based renal denervation (RDN) has emerged as a promising instrumental therapy for hypertension. The interruption of sympathetic nervous system was regarded as a possible mechanism for RDN regulating blood pressure. While the results reflected by renin-angiotensin-aldosterone system (RAAS), catecholamines and electrolytes remained inconsistent and was never systematically assessed. Pubmed, Embase, and Web of Science were comprehensively searched from inception to September 5, 2021. Studies that evaluated the effects of RDN on RAAS, catecholamines, and electrolytes were identified. Primary outcomes were changes in RAAS hormones after RDN, and secondary outcomes involved changes in plasma norepinephrine, serum, and urinary sodium and potassium. Out of 6391 retrieved studies, 20 studies (two randomized controlled studies and 18 observational studies) involving 771 persons were eventually included. Plasma renin activity had a statistically significant reduction after RDN (0.24 ng/mL/h, 95% CI 0.04 to 0.44, P = .02). While no significant change was found regarding plasma aldosterone (1.53 ng/dL, 95% CI -0.61 to 3.67, P = .16), norepinephrine (0.42 nmol/L, 95% -0.51 to 1.35, P = 0.38), serum sodium and potassium (0.16 mmol/L, 95% CI -0.17 to 0.49, P = .34; -0.02 mmol/L, 95% CI -0.09 to 0.04, P = .48, respectively), and urinary sodium and potassium (3.95 mmol/24 h, 95% CI -29.36 to 37.26, P = .82; 10.22 mmol/24 h, 95% CI -12.11 to 32.54, P = .37, respectively). In conclusion, plasma renin activity significantly decreased after RDN, while no significant change was observed in plasma aldosterone, plasma norepinephrine, and serum and urinary electrolytes.
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Affiliation(s)
- Xiangyu Yang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lede Lin
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhipeng Zhang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoping Chen
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
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2
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Lin PL, Lin PY, Huang HP, Vaezi H, Liu LYM, Lee YH, Huang CC, Yang TF, Hsu L, Hsu CF. The autonomic balance of heart rhythm complexity after renal artery denervation: insight from entropy of entropy and average entropy analysis. Biomed Eng Online 2022; 21:32. [PMID: 35610703 PMCID: PMC9131559 DOI: 10.1186/s12938-022-00999-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 05/10/2022] [Indexed: 12/02/2022] Open
Abstract
Background The current method to evaluate the autonomic balance after renal denervation (RDN) relies on heart rate variability (HRV). However, parameters of HRV were not always predictive of response to RDN. Therefore, the complexity and disorder of heart rhythm, measured by entropy of entropy (EoE) and average entropy (AE), have been used to analyze autonomic dysfunction. This study evaluated the dynamic changes in autonomic status after RDN via EoE and AE analysis. Methods Five patients were prospectively enrolled in the Global SYMPLICITY Registry from 2020 to 2021. 24-h Holter and ambulatory blood pressure monitoring (ABPM) was performed at baseline and 3 months after RDN procedures. The autonomic status was analyzed using the entropy-based AE and EoE analysis and the conventional HRV-based low frequency (LF), high frequency (HF), and LF/HF. Results After RDN, the ABPM of all patients showed a significant reduction in blood pressure (BP) and heart rate. Only AE and HF values of all patients had consistent changes after RDN (p < 0.05). The spearman rank-order correlation coefficient of AE vs. HF was 0.86, but AE had a lower coefficient of variation than HF. Conclusions Monitoring the AE and EoE analysis could be an alternative to interpreting autonomic status. In addition, a relative change of autonomic tone, especially an increasing parasympathetic activity, could restore autonomic balance after RDN. Supplementary Information The online version contains supplementary material available at 10.1186/s12938-022-00999-4.
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3
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van Weperen VYH, Vos MA, Ajijola OA. Autonomic modulation of ventricular electrical activity: recent developments and clinical implications. Clin Auton Res 2021; 31:659-676. [PMID: 34591191 PMCID: PMC8629778 DOI: 10.1007/s10286-021-00823-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/12/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE This review aimed to provide a complete overview of the current stance and recent developments in antiarrhythmic neuromodulatory interventions, focusing on lifethreatening vetricular arrhythmias. METHODS Both preclinical studies and clinical studies were assessed to highlight the gaps in knowledge that remain to be answered and the necessary steps required to properly translate these strategies to the clinical setting. RESULTS Cardiac autonomic imbalance, characterized by chronic sympathoexcitation and parasympathetic withdrawal, destabilizes cardiac electrophysiology and promotes ventricular arrhythmogenesis. Therefore, neuromodulatory interventions that target the sympatho-vagal imbalance have emerged as promising antiarrhythmic strategies. These strategies are aimed at different parts of the cardiac neuraxis and directly or indirectly restore cardiac autonomic tone. These interventions include pharmacological blockade of sympathetic neurotransmitters and neuropeptides, cardiac sympathetic denervation, thoracic epidural anesthesia, and spinal cord and vagal nerve stimulation. CONCLUSION Neuromodulatory strategies have repeatedly been demonstrated to be highly effective and very promising anti-arrhythmic therapies. Nevertheless, there is still much room to gain in our understanding of neurocardiac physiology, refining the current neuromodulatory strategic options and elucidating the chronic effects of many of these strategic options.
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Affiliation(s)
- Valerie Y H van Weperen
- Department of Medical Physiology, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands
- UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, UCLA Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, University of California, 100 Medical Plaza, Suite 660, Westwood Blvd, Los Angeles, CA, 90095-1679, USA
| | - Marc A Vos
- Department of Medical Physiology, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands
| | - Olujimi A Ajijola
- UCLA Cardiac Arrhythmia Center, UCLA Neurocardiology Research Center, UCLA Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, University of California, 100 Medical Plaza, Suite 660, Westwood Blvd, Los Angeles, CA, 90095-1679, USA.
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4
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Nantha Kumar N, Nyatsuro K, Ahmad S, Fazmin IT, Saadeh K, Tse G, Jeevaratnam K. Systematic review of renal denervation for the management of cardiac arrhythmias. Clin Res Cardiol 2021; 111:971-993. [PMID: 34748053 PMCID: PMC9424137 DOI: 10.1007/s00392-021-01950-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/04/2021] [Indexed: 01/19/2023]
Abstract
Background In the wake of the controversy surrounding the SYMPLICITY HTN-3 trial and data from subsequent trials, this review aims to perform an updated and more comprehensive review of the impact of renal sympathetic denervation on cardiac arrhythmias. Methods and results A systematic search was performed using the Medline, Scopus and Embase databases using the terms “Renal Denervation” AND “Arrhythmias or Atrial or Ventricular”, limited to Human and English language studies within the last 10 years. This search yielded 19 relevant studies (n = 6 randomised controlled trials, n = 13 non-randomised cohort studies) which comprised 783 patients. The studies show RSD is a safe procedure, not associated with increases in complications or mortality post-procedure. Importantly, there is no evidence RSD is associated with a deterioration in renal function, even in patients with chronic kidney disease. RSD with or without adjunctive pulmonary vein isolation (PVI) is associated with improvements in freedom from atrial fibrillation (AF), premature atrial complexes (PACs), ventricular arrhythmias and other echocardiographic parameters. Significant reductions in ambulatory and office blood pressure were also observed in the majority of studies. Conclusion This review provides evidence based on original research that ‘second generation’ RSD is safe and is associated with reductions in short-term blood pressure and AF burden. However, the authors cannot draw firm conclusions with regards to less prominent arrhythmia subtypes due to the paucity of evidence available. Large multi-centre RCTs investigating the role of RSD are necessary to comprehensively assess the efficacy of the procedure treating various arrhythmias. Graphic abstract ![]()
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Affiliation(s)
- Nakulan Nantha Kumar
- Bristol Medical School, University of Bristol, Bristol, UK.,Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK
| | - Kuda Nyatsuro
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Shiraz Ahmad
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK
| | - Ibrahim T Fazmin
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK.,Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK
| | - Khalil Saadeh
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK.,School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Gary Tse
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK.,Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, China
| | - Kamalan Jeevaratnam
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK.
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5
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Egan BM. Baseline Heart Rate Predicts the Blood Pressure Response to Renal Denervation in Untreated Hypertension. J Am Coll Cardiol 2021; 78:1039-1041. [PMID: 34474736 DOI: 10.1016/j.jacc.2021.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 11/19/2022]
Affiliation(s)
- Brent M Egan
- Department of Medicine, University of South Carolina School of Medicine-Greenville, South Carolina, USA; Improving Health Outcomes, American Medical Association, Greenville, South Carolina, USA.
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6
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Palatini P. Resting Heart Rate as a Cardiovascular Risk Factor in Hypertensive Patients: An Update. Am J Hypertens 2021; 34:307-317. [PMID: 33447842 DOI: 10.1093/ajh/hpaa187] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/20/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023] Open
Abstract
A large body of evidence has shown that resting heart rate (RHR) holds important prognostic information in several clinical conditions. In the majority of the general population studies, a graded association between RHR and mortality from all causes, cardiovascular (CV) disease, ischemic heart disease, and stroke has been observed. These associations appeared even stronger and more consistent in hypertensive patients. Studies performed with 24-hour ambulatory recording have shown that an elevated nighttime heart rate may confer an additional risk on top of office RHR. The mechanisms by which tachycardia alone or in association with sympathetic overactivity induces CV damage are well understood. Fast RHR is a strong predictor of future hypertension, metabolic disturbances, obesity, and diabetes. Several experimental lines of research point to high RHR as a main risk factor for the development of atherosclerosis, large artery stiffness, and CV disease. Elevated RHR is a common feature in patients with hypertension. Thus, there is a large segment of the hypertensive population that would benefit from a treatment able to decrease RHR. Improvement of unhealthy lifestyle should be the first goal in the management of the hypertensive patient with elevated RHR. Most clinical guidelines now recommend the use of combination therapies even in the initial treatment of hypertension. Although no results of clinical trials specifically designed to investigate the effect of RHR lowering in human beings without CV diseases are available, in hypertensive patients with high RHR a combination therapy including a cardiac slowing drug at optimized dose seems a sensible strategy. Tachycardia can be considered both as a marker of sympathetic overactivity and as a risk factor for cardiovascular events. In this sketch, the main cardiovascular and metabolic effects of increased sympathetic tone underlying high heart rate are shown. The link between tachycardia and cardiovascular events can be explained also by the direct hemodynamic action of heart rate on the arteries and the left ventricular (LV) wall.
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Affiliation(s)
- Paolo Palatini
- Department of Medicine, University of Padova, Padua, Italy
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7
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Prado GM, Mahfoud F, Lopes RD, Moreira DAR, Staico R, Damiani LP, Ukena C, Armaganijan LV. Renal denervation for the treatment of ventricular arrhythmias: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2021; 32:1430-1439. [PMID: 33724602 DOI: 10.1111/jce.15004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/13/2021] [Accepted: 02/22/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Ventricular arrhythmias (VAs) are a major cause of morbidity and mortality in patients with heart disease. Recent studies evaluated the effect of renal denervation (RDN) on the occurrence of VAs. We conducted a systematic review and meta-analysis to determine the efficacy and safety of this procedure. METHODS AND RESULTS A systematic search of the literature was performed to identify studies that evaluated the use of RDN for the management of VAs. Primary outcomes were reduction in the number of VAs and implantable cardioverter-defibrillator (ICD) therapies. Secondary outcomes were changes in blood pressure and renal function. Ten studies (152 patients) were included in the meta-analysis. RDN was associated with a reduction in the number of VAs, antitachycardia pacing, ICD shocks, and overall ICD therapies of 3.53 events/patient/month (95% confidence interval [CI] = -5.48 to -1.57), 2.86 events/patient/month (95% CI = -4.09 to -1.63), 2.04 events/patient/month (95% CI = -2.12 to -1.97), and 2.68 events/patient/month (95% CI = -3.58 to -1.78), respectively. Periprocedural adverse events occurred in 1.23% of patients and no significant changes were seen in blood pressure or renal function. CONCLUSIONS In patients with refractory VAs, RDN was associated with a reduction in the number of VAs and ICD therapies, and was shown to be a safe procedure.
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Affiliation(s)
- Gabriela M Prado
- Electrophysiology and Cardiac Arrhythmias Department, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
| | - Felix Mahfoud
- Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Saarland University, Saarbrücken, Germany
| | - Renato D Lopes
- Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
| | - Dalmo A R Moreira
- Electrophysiology and Cardiac Arrhythmias Department, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
| | - Rodolfo Staico
- Electrophysiology and Cardiac Arrhythmias Department, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
| | - Lucas P Damiani
- HCor Research Institute, Hospital do Coração (HCor), São Paulo, Brazil
| | - Christian Ukena
- Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Saarland University, Saarbrücken, Germany
| | - Luciana V Armaganijan
- Electrophysiology and Cardiac Arrhythmias Department, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
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8
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Mancia G, Masi S, Palatini P, Tsioufis C, Grassi G. Elevated heart rate and cardiovascular risk in hypertension. J Hypertens 2021; 39:1060-1069. [PMID: 33399305 DOI: 10.1097/hjh.0000000000002760] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Epidemiological studies have shown that chronically elevated resting heart rate (HR) is significantly associated with organ damage, morbidity and mortality in a wide range of patients including hypertensive patients. Evidence is also available that an increased HR reflects sympathetic nervous system overdrive which is also known to adversely affect organ structure and function and to increase the risk of unfavourable outcomes in several diseases. The causal relationship between elevated HR, organ damage, and cardiovascular outcomes can thus be explained by its relationship with sympathetic cardiovascular influences although evidence of sympathetically-independent adverse effect of HR increases per se makes it more complex. Interventions that target HR by modulating the sympathetic nervous system have therefore a strong pathophysiological and clinical rationale. As most clinical guidelines now recommend the use of combination therapies in patients with hypertension, it might be desirable to consider as combination components drugs which lower HR, if HR is elevated such as, according to guideliines, when it is above 80 b/min.
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Affiliation(s)
- Giuseppe Mancia
- University of Milano-Bicocca and Policlinico di Monza, Milan
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.,National Centre for Cardiovascular Preventions and Outcomes, Institute of Cardiovascular Science, University College London, London, UK
| | - Paolo Palatini
- Department of Medicine, University of Padova, Padua, Italy
| | - Costas Tsioufis
- First Department of Cardiology, National and Kapodistrian university of Athens, Hippocratio Hospital, Athens, Greece
| | - Guido Grassi
- Clinica Medica, University Milano Bicocca, Milan, Italy
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9
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Effects of renal denervation on 24-h heart rate and heart rate variability in resistant hypertension. Clin Res Cardiol 2019; 109:581-588. [DOI: 10.1007/s00392-019-01543-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 08/23/2019] [Indexed: 12/12/2022]
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10
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Saxena M, Shour T, Shah M, Wolff CB, Julu POO, Kapil V, Collier DJ, Ng FL, Gupta A, Balawon A, Pheby J, Zak A, Rull G, O'Brien B, Schmieder RE, Lobo MD. Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success. J Am Heart Assoc 2018; 7:e009151. [PMID: 29895590 PMCID: PMC6220552 DOI: 10.1161/jaha.118.009151] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 04/28/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND Renal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α-1-adrenoceptor-mediated autotransfusion during the Valsalva maneuver. METHODS AND RESULTS In this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within-group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double-blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group. CONCLUSIONS Blood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.
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Affiliation(s)
- Manish Saxena
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Tariq Shour
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Mussadiq Shah
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Christopher B Wolff
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Peter O O Julu
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Vikas Kapil
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - David J Collier
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Fu Liang Ng
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Ajay Gupta
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Armida Balawon
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Jane Pheby
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Anne Zak
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Gurvinder Rull
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
| | - Benjamin O'Brien
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
| | - Roland E Schmieder
- Department of Nephrology and Hypertension, University Hospital, University of Erlangen/Nuremberg, Erlangen, Germany
| | - Melvin D Lobo
- Barts BP Centre of Excellence, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom
- William Harvey Research Institute, Centre for Clinical Pharmacology, Barts NIHR Cardiovascular Biomedical Research Unit, Queen Mary University London, London, United Kingdom
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11
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de Jong MR, Hoogerwaard AF, Adiyaman A, Smit JJJ, Ramdat Misier AR, Heeg JE, van Hasselt BAAM, Van Gelder IC, Crijns HJGM, Lozano IF, Toquero Ramos JE, Javier Alzueta F, Ibañez B, Rubio JM, Arribas F, Porres Aracama JM, Brugada J, Mont L, Elvan A. Treatment of atrial fibrillation in patients with enhanced sympathetic tone by pulmonary vein isolation or pulmonary vein isolation and renal artery denervation: clinical background and study design : The ASAF trial: ablation of sympathetic atrial fibrillation. Clin Res Cardiol 2018; 107:539-547. [PMID: 29487995 DOI: 10.1007/s00392-018-1214-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 02/08/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hypertension is an important, modifiable risk factor for the development of atrial fibrillation (AF). Even after pulmonary vein isolation (PVI), 20-40% experience recurrent AF. Animal studies have shown that renal denervation (RDN) reduces AF inducibility. One clinical study with important limitations suggested that RDN additional to PVI could reduce recurrent AF. OBJECTIVE The goal of this multicenter randomized controlled study is to investigate whether RDN added to PVI reduces AF recurrence. METHODS The main end point is the time until first AF recurrence according to EHRA guidelines after a blanking period of 3 months. Assuming a 12-month accrual period and 12 months of follow-up, a power of 0.80, a two-sided alpha of 0.05 and an expected drop-out of 10% per group, 69 patients per group are required. We plan to randomize a total of 138 hypertensive patients with AF and signs of sympathetic overdrive in a 1:1 fashion. Patients should use at least two antihypertensive drugs. Sympathetic overdrive includes obesity, exercise-induced excessive blood pressure (BP) increase, significant white coat hypertension, hospital admission or fever induced AF, tachycardia induced AF and diabetes mellitus. The interventional group will undergo PVI + RDN and the control group will undergo PVI. RESULTS Patients will have follow-up for 1 year, and continuous loop monitoring is advocated. CONCLUSION This randomized, controlled study will elucidate if RDN on top of PVI reduces AF recurrence.
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Affiliation(s)
- Mark R de Jong
- Department of Cardiology, Isala Hospital, Zwolle, The Netherlands
| | | | - Ahmet Adiyaman
- Department of Cardiology, Isala Hospital, Zwolle, The Netherlands
| | - Jaap Jan J Smit
- Department of Cardiology, Isala Hospital, Zwolle, The Netherlands
| | | | - Jan-Evert Heeg
- Department of Internal Medicine, Isala Hospital, Zwolle, The Netherlands
| | | | | | - Harry J G M Crijns
- Department of Cardiology, Maastricht Universitair Medisch Centrum, Maastricht, The Netherlands
| | - Ignacio Fernández Lozano
- Department of Arrhythmia Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Jorge E Toquero Ramos
- Department of Arrhythmia Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - F Javier Alzueta
- Department of Arrhythmia Unit, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Borja Ibañez
- Department of Cardiology, Hospital Fundación Jimenez Díaz, Madrid, Spain
| | - José M Rubio
- Department of Cardiology, Hospital Fundación Jimenez Díaz, Madrid, Spain
| | - Fernando Arribas
- Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Josep Brugada
- Arrhythmia Unit, Cardiovascular Institute, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Lluís Mont
- Arrhythmia Unit, Cardiovascular Institute, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Arif Elvan
- Department of Cardiology, Isala Hospital, Zwolle, The Netherlands.
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12
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Jamali HK, Waqar F, Gerson MC. Cardiac autonomic innervation. J Nucl Cardiol 2017; 24:1558-1570. [PMID: 27844333 DOI: 10.1007/s12350-016-0725-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 10/25/2016] [Indexed: 10/20/2022]
Abstract
The autonomic nervous system plays a key role in regulating changes in the cardiovascular system and its adaptation to various human body functions. The sympathetic arm of the autonomic nervous system is associated with the fight and flight response, while the parasympathetic division is responsible for the restorative effects on heart rate, blood pressure, and contractility. Disorders involving these two divisions can lead to, and are seen as, a manifestation of most common cardiovascular disorders. Over the last few decades, extensive research has been performed establishing imaging techniques to quantify the autonomic dysfunction associated with various cardiovascular disorders. Additionally, several techniques have been tested with variable success in modulating the cardiac autonomic nervous system as treatment for these disorders. In this review, we summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors. We have also discussed several imaging modalities available to aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques, including pharmacologic and device-based therapies, that have been or are being tested currently.
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Affiliation(s)
- Hina K Jamali
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, P.O. Box 670542, Cincinnati, OH, USA
| | - Fahad Waqar
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, P.O. Box 670542, Cincinnati, OH, USA
| | - Myron C Gerson
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, P.O. Box 670542, Cincinnati, OH, USA.
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Renal denervation reduces office and ambulatory heart rate in patients with uncontrolled hypertension: 12-month outcomes from the global SYMPLICITY registry. J Hypertens 2017; 34:2480-2486. [PMID: 27755390 DOI: 10.1097/hjh.0000000000001085] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The effects on resting and ambulatory heart rate (HR), also regulated by the sympathetic nervous system, are not established. METHODS Herein, we report 12-month outcomes from the Global SYMPLICITY Registry on office and ambulatory HR and BP in patients with uncontrolled hypertension (n = 846). RESULTS HR declined in correlation with the HR at baseline and at 12 months, in particular, in patients in the upper tertile of HR (>74 bpm). BP reduction was similar in the tertiles of HR at baseline. Similar effects were observed when 24-h ambulatory HR and SBP were determined. Office HR was similarly decreased when patients were on a β-blocker or not. Antihypertensive treatment remained unchanged during the 12-month period of the Global SYMPLICITY Registry. CONCLUSION RDN reduces BP independent from HR. A HR reduction is dependent on baseline HR and unchanged by β-blocker treatment. The effects of RDN on SBP and HR are durable up to 1 year. HR reduction might be a target for RDN in patients with high HR at baseline, which needs to be scrutinized in prospective trials.
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Liao SY, Zhen Z, Liu Y, Au KW, Lai WH, Tsang A, Tse HF. Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure. ACTA ACUST UNITED AC 2017; 2:270-281. [PMID: 30062148 PMCID: PMC6034460 DOI: 10.1016/j.jacbts.2017.03.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 01/25/2017] [Accepted: 03/05/2017] [Indexed: 01/14/2023]
Abstract
A porcine model of heart failure was induced by myocardial infarction followed by rapid ventricular pacing for 4 weeks. Catheter-based renal denervation was performed using an expandable basket with 4 electrodes to deliver radiofrequency energy. Histological examination showed significant denervation of the renal arteries after the procedure. Compared with the control group, animals that received renal denervation showed significant improvement of cardiac function as determined by LV ejection fraction, maximum rate of LV pressure rise normalized to instantaneous developed pressure, and reduction of myocardial and renal norepinephrine gradient at 10 weeks after procedure. Renal denervation (RD) is a potential novel nonpharmacological therapy for heart failure (HF). We performed bilateral catheter-based RD in 10 adult pigs and compared them with 10 control subjects after induction of HF to investigate the long-term beneficial effects of RD on left ventricular (LV) function and regional norepinephrine gradient after conventional HF pharmacological therapy. Compared with control subjects, animals treated with RD demonstrated an improvement in LV function and reduction of norepinephrine gradients over the myocardium and kidney at 10-week follow-up. Our results demonstrated that effective bilateral RD decrease regional norepinephrine gradients and improve LV contractile function compared with medical therapy alone.
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Affiliation(s)
- Song-Yan Liao
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Zhe Zhen
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Yuan Liu
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Kai-Wing Au
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Wing-Hon Lai
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Anita Tsang
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China
| | - Hung-Fat Tse
- Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China.,Research Center of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.,Shenzhen Institutes of Research and Innovation, University of Hong Kong, Hong Kong, China
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Tsioufis C, Dimitriadis K, Kasiakogias A, Kalos T, Liatakis I, Koutra E, Nikolopoulou L, Kordalis A, Ella RO, Lau EOY, Grassi G, Papademetriou V, Tousoulis D. Effects of multielectrode renal denervation on elevated sympathetic nerve activity and insulin resistance in metabolic syndrome. J Hypertens 2017; 35:1100-1108. [PMID: 28106665 DOI: 10.1097/hjh.0000000000001262] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE This study aimed to investigate the effects of renal denervation (RDN) on sympathetic nerve activity and insulin resistance in patients with metabolic syndrome. METHODS Seventeen patients fulfilled at least four of five criteria for metabolic syndrome and under stable use of at least two antihypertensive drugs were randomized in 3 : 1 ratio to RDN (n = 13, 12 men, age: 58 ± 7 years) and control groups (n = 4, three men, age: 60 ± 5 years) and followed up for 3 months. Muscle sympathetic nerve activity (MSNA) at rest and during standard 75 g oral glucose tolerance test (OGTT) was assessed. RESULTS In the RDN group, office and average 24-h blood pressures reduced by 16 ± 21/10 ± 11 mmHg (P = 0.01/0.007) and 14 ± 16/5 ± 8 mmHg (P = 0.008/0.03) respectively; waist circumference reduced by 3.1 ± 3.6 cm (P = 0.008); and resting MSNA reduced from 55 ± 9 bursts per minute to 46 ± 8 bursts per minute (P = 0.0008) at month 3 post-RDN. During OGTT, although blunted MSNA responses were noted at baseline throughout the 120-min test, improved MSNA responses with burst frequency increased to 52 ± 8 bursts per minute (P < 0.001 vs. the resting MSNA, n = 13) at 30 min and to 54 ± 8 bursts per minute (P = 0.004 vs. the resting MSNA, n = 10) at 120 min and were observed at month 3 post-RDN. No such improvements were observed in the controls. No significant change was observed in the HOMA-IR in both groups at month 3. CONCLUSION In this pilot study of patients with metabolic syndrome and associated hypertension, RDN reduced elevated sympathetic nerve activity and restored the normal neural response to oral glucose loading.
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Affiliation(s)
- Costas Tsioufis
- aFirst Cardiology Clinic, National and Kapodistrian University of Athens, Hippocration Hospital, Athens, Greece bSt. Jude Medical, Inc., Irvine, California, USA cClinica Medica, University Milano-Biococca dIRCCS Multimedica, Sesto San Giovanni, Milano, Italy eVeterans Affairs and Georgetown University Medical Centers, Washington, District of Columbia, USA
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Bazoukis G, Korantzopoulos P, Tsioufis C. The impact of renal sympathetic denervation on cardiac electrophysiology and arrhythmias: A systematic review of the literature. Int J Cardiol 2016; 220:87-101. [PMID: 27372050 DOI: 10.1016/j.ijcard.2016.06.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 06/12/2016] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Increased central sympathetic activity has a central role in the pathophysiology of cardiac arrhythmias. Despite the recently published negative results regarding the impact of renal sympathetic denervation (RDN) on resistant hypertension treatment, the beneficial effects of this intervention on cardiac arrhythmias seems to be promising. The aim of this systematic review is to analyze the existing data regarding the impact of RDN on atrial and ventricular arrhythmias. METHODS We systematically searched MEDLINE/PubMed database until January 2016 by using the algorithm "renal denervation AND (arrhythmias OR atrial OR ventricular)" without limitations. Additionally, the reference lists of the included studies and the relevant review studies were also manually searched. RESULTS Of the 467 studies yielded from the initial search, 34 were finally included in the systematic review (15 human studies, 18 animal studies and 1 study with both experimental and clinical data). The critical analysis of data from both human and animal studies indicates that RDN can modulate atrial and ventricular electrophysiological properties and exerts favorable effects in the development and recurrence of atrial and ventricular arrhythmias. CONCLUSION In this systematic review we showed that RDN reduces the burden of atrial and ventricular arrhythmias in various experimental and clinical settings. Appropriately designed randomized sham controlled trials are needed in order to elucidate the exact impact of RDN on arrhythmia management.
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Affiliation(s)
- George Bazoukis
- Department of Internal Medicine, General Hospital of Athens "Elpis", Athens, Greece
| | | | - Costas Tsioufis
- First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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Fengler K, Rommel KP, Okon T, Schuler G, Lurz P. Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success. World J Cardiol 2016; 8:436-46. [PMID: 27621771 PMCID: PMC4997524 DOI: 10.4330/wjc.v8.i8.436] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 06/21/2016] [Accepted: 07/14/2016] [Indexed: 02/06/2023] Open
Abstract
Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.
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Affiliation(s)
- Karl Fengler
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Karl Philipp Rommel
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Thomas Okon
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Gerhard Schuler
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
| | - Philipp Lurz
- Karl Fengler, Karl Philipp Rommel, Thomas Okon, Gerhard Schuler, Philipp Lurz, Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, 04289 Leipzig, Germany
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Ukena C, Mahfoud F, Ewen S, Bollmann A, Hindricks G, Hoffmann BA, Linz D, Musat D, Pavlicek V, Scholz E, Thomas D, Willems S, Böhm M, Steinberg JS. Renal denervation for treatment of ventricular arrhythmias: data from an International Multicenter Registry. Clin Res Cardiol 2016; 105:873-9. [PMID: 27364940 DOI: 10.1007/s00392-016-1012-y] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 06/13/2016] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Ventricular arrhythmias (VAs) in patients with chronic heart failure (CHF) are sometimes refractory to antiarrhythmic drugs and cardiac ablation. This study aimed to investigate catheter-based renal sympathetic denervation (RDN) as antiarrhythmic strategy in refractory VA. METHODS These are the first data from a pooled analysis of 13 cases from five large international centers (age 59.2 ± 14.4 years, all male) with CHF (ejection fraction 25.8 ± 10.1 %, NYHA class 2.6 ± 1) presented with refractory VA who underwent RDN. Ventricular arrhythmias, ICD therapies, clinical status, and blood pressure (BP) were evaluated before and 1-12 months after RDN. RESULTS Within 4 weeks prior RDN, a median of 21 (interquartile range 10-30) ventricular tachycardia (VT) or fibrillation (VF) episodes occurred despite antiarrhythmic drugs and prior cardiac ablation. RDN was performed bilaterally with a total number of 12.5 ± 3.5 ablations and without peri-procedural complications. One and 3 months after RDN, VT/VF episodes were reduced to 2 (0-7) (p = 0.004) and 0 (p = 0.006), respectively. Four (31 %) and 11 (85 %) patients of these 13 patients were free from VA at 1 and 3 months. Although BP was low at baseline (116 ± 18/73 ± 13 mmHg), no significant changes of BP or NYHA class were observed after RDN. During follow-up, three patients died from non-rhythm-related causes. CONCLUSIONS In patients with CHF and refractory VA, RDN appears to be safe concerning peri-procedural complications and blood pressure changes, and is associated with a reduced arrhythmic burden.
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Affiliation(s)
- Christian Ukena
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany.
| | - Felix Mahfoud
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany
| | - Sebastian Ewen
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany
| | - Andreas Bollmann
- Abteilung für Rhythmologie, Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig, Leipzig, Germany
| | - Gerhard Hindricks
- Abteilung für Rhythmologie, Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig, Leipzig, Germany
| | - Boris A Hoffmann
- Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Dominik Linz
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany
| | - Dan Musat
- Arrhythmia Institute, Valley Health System, University of Rochester School of Medicine and Dentistry, New York, NY, USA
| | - Valerie Pavlicek
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany
| | - Eberhard Scholz
- Innere Medizin III (Kardiologie, Angiologie, Pneumologie), Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Dierk Thomas
- Innere Medizin III (Kardiologie, Angiologie, Pneumologie), Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Stephan Willems
- Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Michael Böhm
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66421, Homburg, Saar, Germany
| | - Jonathan S Steinberg
- Arrhythmia Institute, Valley Health System, University of Rochester School of Medicine and Dentistry, New York, NY, USA
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Papademetriou V, Doumas M, Tsioufis C. Renal Sympathetic Denervation: Hibernation or Resurrection? Cardiology 2016; 135:87-97. [DOI: 10.1159/000446909] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 05/12/2016] [Indexed: 11/19/2022]
Abstract
The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research.
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Pourafshar N, Karimi A, Anderson RD, Alaei-Andabili SH, Kandzari DE. Renal Denervation: Past, Present, and Future. CARDIOVASCULAR INNOVATIONS AND APPLICATIONS 2016. [DOI: 10.15212/cvia.2016.0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial. Clin Res Cardiol 2016; 105:592-600. [PMID: 26728060 DOI: 10.1007/s00392-015-0955-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 12/18/2015] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Despite the ongoing debate on the role of renal sympathetic denervation (RSD) in the management of therapy-resistant hypertension, little is known about its possible effects on exercise blood pressure (BP), a known predictor for future cardiovascular events. We sought to evaluate the effect of RSD on exercise BP in a randomized, sham-controlled trial in patients with mild hypertension. METHODS AND RESULTS Patients with therapy-resistant mild hypertension (defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement) were randomized to either radiofrequency-based RSD or a sham procedure. Patients underwent cardiopulmonary exercise testing at baseline and after 6 months. Of the 71 patients randomized, data from cardiopulmonary exercise testing were available for 48 patients (22 in the RSD group, 26 in the sham group). After 6 months, patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline (-14.2 ± 26.1 mmHg, p = 0.009). In contrast, no change was observed in the sham group (0.6 ± 22.9 mmHg, p = 0.45, p = 0.04 for between-group comparison). When analyzing patients with exaggerated baseline exercise BP only, the effect was even more pronounced (RSD vs. sham -29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg, p = 0.008). CONCLUSION Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure.
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Schirmer SH, Sayed MMYA, Reil JC, Lavall D, Ukena C, Linz D, Mahfoud F, Böhm M. Atrial Remodeling Following Catheter-Based Renal Denervation Occurs in a Blood Pressure- and Heart Rate-Independent Manner. JACC Cardiovasc Interv 2015; 8:972-80. [PMID: 26003031 DOI: 10.1016/j.jcin.2015.02.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 01/21/2015] [Accepted: 02/12/2015] [Indexed: 11/28/2022]
Abstract
OBJECTIVES This study sought to investigate left atrial (LA) remodeling in relation to blood pressure (BP) and heart rate (HR) after renal sympathetic denervation (RDN). BACKGROUND In addition to reducing BP and HR in certain patients with hypertension, RDN can decrease left ventricular (LV) mass and ameliorate LV diastolic dysfunction. METHODS Before and 6 months after RDN, BP, HR, LV mass, left atrial volume index (LAVI), diastolic function (echocardiography), and premature atrial contractions (PAC) (Holter electrocardiogram) were assessed in 66 patients with resistant hypertension. RESULTS RDN reduced office BP by 21.6 ± 3.0/10.1 ± 2.0 mm Hg (p < 0.001), and HR by 8.0 ± 1.3 beats/min (p < 0.001). At baseline, LA size correlated with LV mass, diastolic function, and pro-brain natriuretic peptide, but not with BP or HR. Six months after RDN, LAVI was reduced by 4.0 ± 0.7 ml/kg/m(2) (p < 0.001). LA size decrease was stronger when LAVI at baseline was higher. In contrast, the decrease in LAVI was not dependent on LV mass or diastolic function (E/E' or E/A) at baseline. Furthermore, LAVI decreased without relation to decrease in systolic BP or HR. Additionally, occurrence of PAC (median of >153 PAC/24 h) was reduced (to 68 PAC/24 h) by RDN, independently of changes in LA size. CONCLUSIONS In patients with resistant hypertension, LA volume and occurrence of PAC decreased 6 months after RDN. This decrease was independent of BP and HR at baseline or the reduction in BP and HR reached by renal denervation. These data suggest that there is a direct, partly BP-independent effect of RDN on cardiac remodeling and occurrence of premature atrial contractions.
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Affiliation(s)
- Stephan H Schirmer
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
| | - Marwa M Y A Sayed
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Jan-Christian Reil
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Daniel Lavall
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Christian Ukena
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Dominik Linz
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Felix Mahfoud
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Michael Böhm
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
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Olsen LK, Kamper AL, Svendsen JH, Feldt-Rasmussen B. Renal denervation. Eur J Intern Med 2015; 26:95-105. [PMID: 25676808 DOI: 10.1016/j.ejim.2015.01.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 01/14/2015] [Accepted: 01/23/2015] [Indexed: 01/18/2023]
Abstract
PURPOSE OF REVIEW Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS The Symplicity HTN-1 (2009) and HTN-2 (2010) studies re-introduced an old treatment approach for resistant hypertension and showed that catheter-based RDN was feasible and resulted in substantial blood pressure (BP) reductions. However, they also raised questions of durability of BP reduction, correct patient selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY Initial studies demonstrated that RDN in patients with resistant hypertension was both feasible and safe and indicated that RDN may lead to impressive reductions in BP. However, recent controlled studies question the BP lowering effect of RDN treatment. Large-scale registry data still supports the favorable BP reducing effect of RDN. We suggest that, in the near future, RDN should not be performed outside clinical studies. The degree of denervation between individual operators and between different catheters and techniques used should be clarified. The major challenge ahead is to identify which patients could benefit from RDN, to clarify the lack of an immediate procedural success parameter, and to establish further documentation of overall effect of treatment such as long-term cardiovascular morbidity and mortality.
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Affiliation(s)
- Lene Kjær Olsen
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Anne-Lise Kamper
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Jesper Hastrup Svendsen
- Deparment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Danish Arrhythmia Research Centre, University of Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
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Abstract
After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial—Symplicity HTN-3—to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25–30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity–mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already “knocking at the door”, the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.
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Linz D, Hunnik AV, Ukena C, Mahfoud F, Ewen S, Verheule S, Böhm M, Schotten U. Effects of renal denervation on atrial arrhythmogenesis. Future Cardiol 2014; 10:813-22. [DOI: 10.2217/fca.14.43] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
ABSTRACT Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity and mortality. In addition to mechanisms such as atrial stretch and atrial remodeling, the activity of the autonomic nervous system has also been suggested to contribute to the progression from paroxysmal to persistent atrial fibrillation. Catheter-based renal denervation was introduced as a minimally invasive approach to reduce renal and whole body sympathetic activation with accompanying blood pressure reduction and left-ventricular morphological and functional improvement in drug-resistant hypertension. This review focuses on the potential effects of renal denervation on different arrhythmogenic mechanisms in the atrium and discusses potential anti-remodeling effects in atrial fibrillation patients with hypertension, heart failure and sleep apnea.
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Affiliation(s)
- Dominik Linz
- Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Germany
| | - Arne van Hunnik
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
| | - Christian Ukena
- Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Germany
| | - Felix Mahfoud
- Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Germany
| | - Sebastian Ewen
- Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Germany
| | - Sander Verheule
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
| | - Michael Böhm
- Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Germany
| | - Ulrich Schotten
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
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26
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Wang Y. Ethnicity and sympathetic tone: predictors of the blood pressure response to renal denervation? Nat Rev Cardiol 2014; 11:638. [DOI: 10.1038/nrcardio.2014.70-c1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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