Short-term effects of catheter-based renal denervation on cardiac sympathetic drive and cardiac baroreflex function in heart failure

Booth, Lindsea C.; Schlaich, Markus P.; Nishi, Érika E.; Yao, Song T.; Xu, Jianzhong; Ramchandra, Rohit; Lambert, Gavin W.; May, Clive N.

doi:10.1016/j.ijcard.2015.03.440

Cited by 21 publications

(26 citation statements)

References 48 publications

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“…Although producing a modest fall in arterial pressure in 29 obese patients with metabolic syndrome treated with a maximum of one antihypertensive drug, renal nerve ablation failed to decrease MSNA at a 6 mo follow-up (84). In an ovine model of heart failure, catheter-based renal denervation did not reduce elevated levels of cardiac sympathetic nerve activity when measured 24 h after renal denervation (7).…”

Section: Other Potential Determinants Of the Antihypertensive Responsmentioning

confidence: 88%

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Iliescu

Lohmeier

Tudorancea

et al. 2015

American Journal of Physiology-Renal Physiology

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When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYM-PLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans. denervation; hypertension; pathophysiology; renal nerves; resistance RESISTANT HYPERTENSION IS defined as failure to achieve a guideline-driven blood pressure of less than 140/90 mmHg in patients who are adherent to maximally tolerated doses of at least three antihypertensive drugs, including a diuretic appropriate for kidney function (13). Population-based studies published over the last decade indicate that anywhere from 3 to 12% of hypertensive patients in the United States have resistant hypertension, despite the abundance of efficacious blood pressure-lowering agents belonging to over seven drug classes (11,20,68). Moreover, in addition to the cardiovascular mortality risk directly linked to the extent of blood pressure elevation, resistant hypertensive patients frequently have additional risk factors such as obesity, diabetes, chronic kidney disease, and age over 55 and are therefore more likely to die from stroke, myocardial infarction, heart failure, and end-stage renal disease (47, 76).Since increased sympathetic activity was believed to be present in many patients with resistant hypertension, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication and was introduced for clinical use 6 years ago. In the open label, uncontrolled SYMPLICITY HTN-1 and SYMPLICITY HTN-2 trials, undertaken in patients with resistant hypertension, redu...

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Section: Other Potential Determinants Of the Antihypertensive Responsmentioning

confidence: 88%

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Iliescu

Lohmeier

Tudorancea

et al. 2015

American Journal of Physiology-Renal Physiology

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“…A recent study employed catheter-based renal denervation after the development of CHF in sheep (Booth et al, 2015b ). Despite convincing evidence of complete functional afferent and efferent renal denervation as well as a drop in blood pressure, renal denervation did not decrease cardiac sympathetic tone or improve cardiac baroreflex gain in CHF sheep.…”

Section: Afferent Renal Sympathetic Nerve Activity In Chfmentioning

confidence: 99%

“…After denervation, renal norepinephrine spillover was reduced by an average of 47%, but this response was highly variable between subjects. Much better results have been achieved in both sheep and pigs (Booth et al, 2015b ), but the fact that the renal nerves do not form a network around the main renal artery in man may render such complete denervation impossible (Oldham, 1950 ). The partial efficacy of catheter-based techniques in patients contrasts from surgical denervation, which consistently and completely eliminates renal norepinephrine in all species.…”

Section: Catheter-based Renal Denervationmentioning

confidence: 99%

The renal nerves in chronic heart failure: efferent and afferent mechanisms

2015

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The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF.

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“…In addition, a recent study investigating the effects of surgical RDN in rats with cardiac dysfunction secondary to chronic pressure overload showed that RDN reduced myocardial fibrosis, increased cardiac β-adrenergic receptor expression and decreased cardiac AT-1 receptor levels (Li et al, 2015 ). In pacing-induced ovine HF, the high resting level of CSNA was not reduced shortly after catheter-based RDN, but the baroreflex-mediated increase in CSNA in response to the fall in BP was inhibited following the procedure (Booth et al, 2015c ). This lack of a reflex increase in CSNA resulted from a leftward shift of the CSNA arterial baroreflex curve (Booth et al, 2015c ).…”

Section: Ablation Of the Renal Nerve Fibers In Heart Failure: Evidencmentioning

confidence: 99%

“…In pacing-induced ovine HF, the high resting level of CSNA was not reduced shortly after catheter-based RDN, but the baroreflex-mediated increase in CSNA in response to the fall in BP was inhibited following the procedure (Booth et al, 2015c ). This lack of a reflex increase in CSNA resulted from a leftward shift of the CSNA arterial baroreflex curve (Booth et al, 2015c ). These findings indicate that RDN can have beneficial cardiac effects in experimental HF, but further studies are required to determine the mechanisms involved.…”

Section: Ablation Of the Renal Nerve Fibers In Heart Failure: Evidencmentioning

confidence: 99%

The role of the renal afferent and efferent nerve fibers in heart failure

2015

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Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

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Short-term effects of catheter-based renal denervation on cardiac sympathetic drive and cardiac baroreflex function in heart failure

Cited by 21 publications

References 48 publications

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

Renal denervation for the treatment of resistant hypertension: review and clinical perspective

The renal nerves in chronic heart failure: efferent and afferent mechanisms

The role of the renal afferent and efferent nerve fibers in heart failure

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