First-in-man safety evaluation of renal denervation for chronic systolic heart failure: Primary outcome from REACH-Pilot study

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Abstract

Background

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.

Method

7 patients (mean age 69 years) with chronic systolic heart failure (mean BP on referral 112/65 mm Hg) 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.

Results

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 mm Hg, p = 0.35; Δdiastolic − 0.6 ± 4.0 mm Hg, 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.

Conclusions

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.

Introduction

Chronic heart failure affects around 100 million people worldwide imposing a significant burden on health care systems throughout the world. Even though symptoms are improved by heart failure therapy, they remain significantly disabling for many patients. Chronic over-activation of the sympathetic nervous system, is a major component of heart failure [1], [2], [3] and involves efferent and afferent pathways between brain and many organs [4].

A new therapy directly targeting nerve traffic—renal artery denervation—has been shown to be effective in drug-resistant hypertension, with an average drop in blood pressure of 33/12 mm Hg [5], [6]. Although in principle this intervention could be beneficial for improving the neurohormonal dysregulation of chronic heart failure [7], [8], there are concerns in practice because heart failure patients typically have normal or low blood pressure, and might therefore become symptomatically worse following renal denervation should blood pressure be lowered further.

We have therefore conducted a first-in-man study of 7 patients with chronic systolic heart failure, undergoing bilateral renal denervation, with an intensive protocol of observation and assessment comprising a 5-day hospital stay post procedure and 6 months of regular outpatient follow up.

Section snippets

Recruitment

In this first-in-man exploration, we sought to address a stable population of chronic systolic heart failure patients taking full prognostic therapy who would be willing to undergo prolonged inpatient assessment and intensive serial outpatient evaluation.

7 patients were recruited from the heart failure clinics of the campuses of Imperial College Academic Health Science Centre. Patients were required to have chronic symptomatic systolic heart failure (NYHA class III or IV) on maximal tolerated

Results

Bilateral denervation was successfully performed in all 7 patients. A minimum of 4 denervation therapies were delivered to each artery. There were no access site or other arterial complications associated with the procedure.

Discussion

In this first-in-man study of bilateral renal denervation in chronic systolic heart failure, there were no procedural complications or symptomatic adverse effects. The 5-day inpatient monitoring revealed no acute deleterious haemodynamic disturbances. In the longer term there was a trend towards blood pressure reduction over the 6 month follow up period which was small and did not achieve statistical significance. In all subjects markers of renal function remained stable with no clinical or

Conclusions

Bilateral renal denervation can be conducted safely in patients with chronic systolic heart failure. It appears well tolerated, with no haemodynamic disturbance during the immediate 5 days following the procedure nor any marked worsening in symptoms or renal function over a 6-month follow up period. A randomised, placebo-controlled blinded trial is required to evaluate whether renal artery denervation can achieve symptomatic improvements and increase objective functional measures such as walking

Conflict of interest

J.E. Davies and D.P. Francis are consultants for Medtronic Corp. and P. Sobotka receives royalties as a developer of the Ardian catheter system. No other author has a conflict of interest to declare.

Acknowledgements

R. Petraco (FS/11/46/28861), J.E. Davies (FS/05/006), and D.P. Francis (FS/10/038) are supported by the British Heart Foundation. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

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