Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial

Mahfoud, Felix; Urban, Daniel J.; Teller, Desiree; Linz, Dominik; Stawowy, Philipp; Hassel, J; Fries, Peter; Dreysse, Stephan; Wellnhofer, Ernst; Schneider, Günther; Buecker, Arno; Schneeweis, Christopher; Doltra, Adelina; Schlaich, Markus P.; Esler, Murray; Fleck, Eckart; Böhm, Michael; Kelle, Sebastian

doi:10.1093/eurheartj/ehu093

Cited by 133 publications

(105 citation statements)

References 64 publications

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“…Similarly, patients enrolled in other RDN trials show regression of target organ damage, including reduced arterial stiffness 32 and left ventricular hypertrophy. 33 Hypertension is widely considered to represent a proinflammatory milieu, which may contribute to atherosclerosis and its complication frequently encountered in this patient cohort. While there is abundant experimental evidence to suggest an important role of inflammatory processes in the pathogenesis of hypertension and its cardiovascular consequences, direct evidence in humans for such an intricate interaction was scarce and less convincing yet.…”

Section: Discussionmentioning

confidence: 99%

Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate Formation

et al. 2017

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H ypertension contributes significantly to the high cardiovascular morbidity and mortality rates worldwide. While acknowledging the complexity and multifactorial pathogenesis of hypertension, it has been suggested that activation of the sympathetic nervous system (SNS) is an important contributor in at least 50% of cases.1 Persistent sympathetic activation initiates and sustains elevated blood pressure (BP) via various pathways, including renal (sodium and water retention), humoral (activation of the renin-angiotensin system), peripheral (vasoconstriction), and other mechanisms. 1 Sustained sympathetic activation has also been closely linked to a range of clinical adverse consequences, such as left ventricular hypertrophy, progression of renal disease, and others. Catheter-based renal denervation (RDN) is a relatively novel therapeutic approach used primarily in the context of resistant hypertension aimed at targeting sympathetic overactivity commonly encountered in these patients. 2 Indeed, we and others have demonstrated that RDN reduces both renal sympathetic activity (by ≤42% in obese hypertensive dogs and by ≤47% in patients with resistant hypertension 3,4 ) and muscle sympathetic nerve Abstract-Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte-platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1β (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of be...

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Section: Discussionmentioning

confidence: 99%

Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate Formation

et al. 2017

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“…However, the results of this trial are inconsistent with clinical and preclinical experience, indicating the need to more clearly understand the reasons for these disparate observations. 9,12,13 Further data are also needed to confirm the reported favorable effects of RDN on organ damage and other conditions often associated with hypertension (left ventricular hypertrophy, 14,15 increased urinary albumin excretion, 16,17 and atrial fibrillation 18 ) in which sympathetic hyperactivity may play a role in addition to and independently of the BP increase. 5 Because RDN is an interventional procedure that may expose patients to some risks and could increase costs, large databases on safety and efficacy in clinical practice settings, without the strict inclusion and exclusion criteria and site selection used in clinical trials, are needed.…”

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confidence: 99%

First Report of the Global SYMPLICITY Registry on the Effect of Renal Artery Denervation in Patients With Uncontrolled Hypertension

et al. 2015

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Abstract-This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in realworld patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were −11.6±25.3 and −6.6±18.0 mm Hg for all patients (P<0.001 for both) and −20.3±22.8 and −8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. Clinical Trial Registration-URL: www.clinicaltrials.gov. Unique identifier: NCT01534299 ) in which sympathetic hyperactivity may play a role in addition to and independently of the BP increase. 5Because RDN is an interventional procedure that may expose patients to some risks and could increase costs, large databases on safety and efficacy in clinical practice settings, without the strict inclusion and exclusion criteria and site selection used in clinical trials, are needed. The Global SYMPLICITY registry (GSR) 19 will provide data on periprocedural and renal safety as well as the effectiveness of BP reduction in such a real-world population of patients undergoing RDN. Herein, the GSR investigators report on the 6-month follow-up of the largest group of hypertensive patients to undergo RDN in an uncontrolled global clinical setting. Methods DesignThis analysis is based on 998 patients with complete safety and office BP data at baseline and 6 months of follow-up, who underwent RDN from February 1, 2012, to September 9, 2013. One-hundred thirtyfour centers in Canada, Western Europe, Latin America, Eastern Europe, South Africa, Middle East, Asia, Australia, and New Zealand were involved (see online-only Data Supplement).The study design of the prospective, open-label, multicenter GSR has been published previously. 19 In brief, the registry will include ≤5000 patients with hy...

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“…Another reason may be that while eutrophic remodeling is the earliest event taking place in the crosstalk between micro and macrocirculation, anticipating the development of prognostically important features (such as left ventricular hypertrophy), a decrease in SNS activity could be responsible of the hypotrophic pattern changes. Renal denervation, as well as BAT, have already been shown to determine a regression of left ventricular hypertrophy, mainly due to myocyte hypertrophy reversal [13,14]. Finally, the role of baroreflex stimulation may explain the different long term retinal response in our cohorts.…”

Section: Discussionmentioning

confidence: 79%

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients

Rosenbaum

Kanagasabapathy

Girerd

2017

Annales de Cardiologie et d'Angéiologie

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Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial

Abstract: Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

Cited by 133 publications

References 64 publications

Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate Formation

Renal Denervation Reduces Monocyte Activation and Monocyte–Platelet Aggregate Formation

First Report of the Global SYMPLICITY Registry on the Effect of Renal Artery Denervation in Patients With Uncontrolled Hypertension

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients

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