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      Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure

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          Abstract

          A growing number of clinical studies suggest that in heart failure renal denervation (RDN) has beneficial effects on the autonomic control of the heart. There is also experimental evidence that surgical RDN improves sodium handling and clearance in heart failure. The aim of this study was to determine the effects of catheter-based RDN on the sympathetic and parasympathetic control of the heart, and salt and water handling capacity of the kidneys, in sheep with established heart failure. A randomized, controlled study was conducted in 10 sheep with heart failure (ejection fraction<40%) induced by rapid ventricular pacing. Sheep underwent either bilateral RDN using the Symplicity denervation system or sham denervation and were studied 1 and 6 weeks after RDN. In established ovine heart failure, at 6 weeks after catheter-based RDN, heart rate significantly decreased, estimates of resting and maximal parasympathetic control of heart rate increased, and cardiac sympathetic nerve activity decreased. Compared with sham denervation, there was an increase in the resting sodium and water excretion 6 weeks after catheter-RDN and an improved ability of the kidneys to excrete a nonhypertensive saline load. After catheter-based RDN, renal norepinephrine levels were reduced by 70% compared with sham denervation. In established heart failure, RDN induced a beneficial shift in both arms of the autonomic nervous control of the heart and improved the ability of the kidneys to excrete sodium and water. Thus, effective catheter-based RDN may be beneficial to both the heart and kidneys in heart failure.

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          Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

          Salim S. Virani, Alvaro Alonso, Hugo Aparicio … (2021)
          The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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            First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study.

            Eduardo A. Barrón, Michael D. Hughes, Charlotte Manisty … (2013)
            Sympathetic overactivation, is reduced by renal denervation in drug-resistant hypertension. A similar role for renal denervation in heart failure remains unstudied, partly due to the concern about potential concomitant deleterious blood pressure reductions. This pilot study evaluated the safety of renal denervation for heart failure using an intensive follow-up protocol. 7 patients (mean age 69 years) with chronic systolic heart failure (mean BP on referral 112/65 mmHg) on maximal tolerated heart failure therapy underwent bilateral renal denervation May-July 2011. Patients were admitted for pre-procedure baseline assessments and in-patient observation for 5 days following denervation. Follow-up was weekly for 4 weeks, and then monthly for 6 months. No significant haemodynamic disturbances were noted during the acute phase post renal denervation. Over 6 months there was a non-significant trend to blood pressure reduction (Δsystolic -7.1 ± 6.9 mmHg, p=0.35; Δdiastolic -0.6 ± 4.0 mmHg, p=0.88). No hypotensive or syncopal episodes were reported. Renal function remained stable (Δcreatinine -5.7 ± 8.4 μmol/l, p=0.52 and Δurea -1.0 ± 1.0 mmol/l, p=0.33). All 7 patients described themselves as symptomatically improved. The six minute walk distance at six months was significantly increased (Δ=27.1 ± 9.7 m, p=0.03), with each patient showing an increase. This study found no procedural or post procedural complications following renal denervation in patients with chronic systolic heart failure in 6 months of intensive follow-up. Results suggested improvements in both symptoms and exercise capacity, but further randomised, blinded sham-controlled clinical trials are required to determine the impact of renal denervation on morbidity and mortality in systolic heart failure. These data suggest such trials will be safe. ClinicalTrial.gov NCT01584700 Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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              Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep.

              Lindsea C Booth, Erika E. Nishi, Song T Yao … (2015)
              Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed. © 2014 American Heart Association, Inc.
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                Author and article information

                Contributors
                Roberto B. Pontes: (View ORCID Profile)
                Song T. Yao: (View ORCID Profile)
                Yugeesh R. Lankadeva: (View ORCID Profile)
                Junko Kosaka: (View ORCID Profile)
                Gavin W. Lambert: (View ORCID Profile)
                Clive N. May: (View ORCID Profile)
                Journal
                Title: Hypertension
                Abbreviated Title: Hypertension
                Publisher: Ovid Technologies (Wolters Kluwer Health)
                ISSN (Print): 0194-911X
                ISSN (Electronic): 1524-4563
                Publication date Created: September 2021
                Publication date (Print): September 2021
                Volume: 78
                Issue: 3
                Pages: 706-715
                Affiliations
                [1 ]Florey Institute of Neuroscience and Mental Health (L.C.B., R.A.U.d.S., R.B.P., S.T.T., S.G.H., Y.R.L., J.K., C.N.M.), University of Melbourne, Parkville, Victoria, Australia.
                [2 ]Department of Physiology, Cardiovascular Division, Federal University of São Paulo, Brazil (R.B.P.).
                [3 ]Department of Anatomy and Physiology, MDHS (S.T.Y.), University of Melbourne, Parkville, Victoria, Australia.
                [4 ]Department of Anesthesiology and Resuscitology, Okayama University Hospital, Japan (J.K.).
                [5 ]Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Hawthorn, Victoria, Australia (N.E., G.W.L.).
                [6 ]Dobney Hypertension Centre, School of Medicine-Royal Perth Hospital Unit, University of Western Australia, Perth (M.P.S.).
                Article
                DOI: 10.1161/HYPERTENSIONAHA.120.16054
                PubMed ID: 34333989
                SO-VID: dffb05b1-2d0b-4c96-8e4a-d3db5da9fa1f
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