Chronic heart failure (CHF) affects about 100 million patients throughout the world, and has a five-year survival rate of only 50%, although drug therapy can improve symptoms. As an important factor in the genesis and development of heart failure (HF), sympathetic hyperactivity is directly correlated with the severity and prognosis of HF.1

Recently, it has been reported that a novel catheter-based renal sympathetic denervation (RDN) technique to ablate the renal afferent and efferent nerves2 can reduce excessive sympathetic nerve activation and may have a potential therapeutic effect in diseases associated with sympathetic activation.3 In some studies on hypertension, RDN has been found to lower blood pressure (BP) in patients with resistant hypertension, with a mean reduction of 33/12 mmHg.4,5 A previous study confirmed that RDN using a 3.5F Symplicity ablation catheter can extend the 6-min walk distance of patients with HF,6 but does not improve ejection fraction (EF) and left ventricular volume as shown by echocardiography. Our study group has demonstrated in preliminary animal experiments that percutaneous RDN using a 5F ablation catheter (Medtronic Inc., Dublin, Ireland) can improve cardiac function and reduce left ventricular volume in pigs with rapid pacing-induced HF.7 In the present study, a 5F ablation catheter was used for RDN in patients with CHF, and safety parameters such as cardiac function, exercise tolerance, BP, and creatinine (Cr) were assessed.

All fourteen patients underwent bilateral RDN and completed six-month follow-up.

Safety of renal denervation for treating heart failure

After bilateral RDN, neither hypotension nor syncope was observed during six-month follow-up, and renal function and Cr levels remained stable. Mean BP was 123.2±10.5/72.9±7.5 mmHg (significantly different from that of pre-RDN for all fourteen patients) (Table 3, Figure 1).

Figure 1.

Blood pressure of heart failure patients undergoing renal denervation during follow-up. RDN: renal denervation.

(0.07MB).

Assessment of symptoms and six-min walk test distance

During the follow-up period, all patients showed significantly improvement in HF symptoms such as chest distress and shortness of breath, and the number of hospitalizations due to HF was also significantly reduced (Table 3). The 6-min walk distance increased significantly, from 152.9±38.0 m before RDN to 334.3±94.4 m six months after RDN (p<0.001) (Figure 2).

Figure 2.

Six-minute walk distance in heart failure patients undergoing renal denervation. RDN: renal denervation.

(0.06MB).

In 2009 and 2010, a series of trials demonstrated that RDN is likely to be an effective therapeutic method for treating resistant hypertension.4,5 However, the more recent HTN-3 trial,8 frustratingly, showed that RDN had a similar BP-lowering effect to that in the sham group, leading to widespread concern about the effectiveness of RDN. However, this has not spelled the end of studies on RDN, especially those on its effects in HF.6,9,10 RDN can block the renal sympathetic nerves, inhibiting activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), and is thus regarded as a possible approach for the treatment of HF.

During the follow-up period in our study, all fourteen patients had increased EF on echocardiography. Results of the 6-min walk test indicated significant improvements in cardiac function and exercise tolerance after RDN. The dosage of loop diuretics was also reduced due to improved control of symptoms and signs of HF.

The results of this study showed that there were no complications such as RAS or renal artery dissection in these HF patients following bilateral RDN. During the six-month follow-up period, hypotensive events were not observed and renal function did not change significantly.

The Renal Artery Denervation in Chronic Heart Failure (REACH-Pilot) trial in seven patients with HF was another study on the effects of percutaneous RDN. The trial indicated that RDN improved 6-min walk distance and exercise tolerance, consistent with the results of the present study. However, the present study also demonstrated significant improvements in EF and left ventricular volume on echocardiography, unlike the REACH-Pilot study. This discrepancy is likely to be related to the ablation catheter used and to differences in procedures. A 5F ablation catheter was used in the present study. Compared with the 3.5F Symplicity catheter (Medtronic Inc.), a 5F catheter makes more contact with blood vessels and the radiofrequency energy more easily penetrates the vessel wall to ablate nerve plexuses in the adventitia. Additionally, thermal energy is more likely to accumulate and cause vascular stenosis when a 5F ablation catheter is used compared with smaller sizes.

HF of both hypertensive and nonhypertensive etiology was included in this study. The results demonstrated that RDN is more effective in the improvement of cardiac function (especially EF) in patients with hypertensive HF, probably due to the BP-lowering effect of RDN, indicating that RDN may most benefit HF patients with hypertensive heart disease.

Numerous studies have explored the relationship between RDN and HF. Nozawa et al.11 reported that RDN performed before MI significantly reduced ventricular filling pressure and improved cardiac function in rats. More recently, Clayton et al.12 confirmed in a rapid pacing-induced rabbit HF model the dependence of angiotensin receptor expression on sympathetic nerve activity. They also observed an increase in the expression of angiotensin II type 1 receptor in renal cortical vessels and a decrease in the expression of angiotensin II type 2 receptor in HF rabbits, both of which were diminished by renal denervation. Similarly, Schiller et al.13 reported the inhibition of sympathetic nerve activity by unilateral RDN in a rabbit model of rapid pacing-induced HF, which was beneficial for cardiac sympathovagal balance in HF rabbits. All these results support the idea that RDN can inhibit activation of the sympathetic system and the RAAS to improve cardiac function.

The 2016 European Society of Cardiology Congress made it clear that despite the disappointing results of HTN-3, research into RDN will continue14. The clinical efficacy of RDN in the treatment of heart failure is supported by some ongoing studies.15

The results of the present study indicate that RDN using a 5F ablation catheter can improve cardiac function, reduce HF symptoms and signs, and enhance exercise tolerance in patients with HF. But a large-scale, long-term, randomized controlled trial is needed to confirm the results, because the present study was only a clinical observation with a small sample and a short follow-up period (six months).

This was a single-center, non-blinded, non-randomized, non-controlled clinical study with a small patient sample and without exclusion of possible biases.

RDN is a promising new technique for the treatment of severe HF, but more long-term research and clinical evidence are needed. It can effectively increase EF on echocardiography and improve exercise tolerance. Its effects are especially clear in hypertensive patients, which may be due to its antihypertensive effects.

The study was funded by the National Natural Science Foundation of China Youth Project (81303145), Shanghai Municipal Commission of Health and Family Planning Key Project (20134003), Shanghai Municipal Commission of Health and Family Planning General Program (201440492), and the Putuo District Shanghai independent innovation project (KW12201).

The authors have no conflicts of interest to declare.