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Heart failure is a complicated pathophysiological syndrome. Balancing autonomic nervous activity and inhibiting myocardial remodeling are important methods for improving long-term efficacy in patients with heart failure. Pharmacologic management has been greatly developed, for example, the use of β-blockers is intended to inhibit the toxic effect of sympathetic activation on the heart and has become a classic treatment for heart failure. However, the incidence of heart failure is still on the rise and survivability is persistently reduced. In recent years, surgical treatments for inhibiting excessive activation of the sympathetic nervous system have emerged, such as vagus nerve stimulation, baroreceptor activation therapy. Some methods have obtained significant benefits in animal experiments and preliminary clinical study. It is essential to further verify the role of the above treatments in patients with heart failure in clinical trials.
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Objective: To observe the effectiveness of catheter-based renal sympathetic denervation (RDN) for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter. Methods: Thirty patients with resistant hypertension received RDN between January 2013 and December 2015. They were randomly divided into two groups: general ablation catheter group and microtube-irrigated ablation catheter group, with 15 cases in each group. 5 F temperature-controlled catheter was used in the general ablation catheter group. 5 F microtube-irrigated ablation catheter (microtubes at the head) was used in the microtube-irrigated ablation catheter group. Cold saline was irrigated for mapping and ablation. All patients were followed up for 9 months. Clinic blood pressure, 24 h ambulatory blood pressure, biochemical tests and cardiac function were measured at baseline and during follow-up. Results: RDN was successfully performed in all patients. At the 9-month follow-up, the decrease of 24 h ambulatory systolic blood pressure (SBP) in the microtube-irrigated ablation catheter group was more obvious than that in the general ablation catheter group ([34.67±13.02] mmHg vs [17.00 ± 16.74] mmHg, P<0.01; 1 mmHg=0.133 kPa). The 24 h ambulatory diastolic blood pressure (DBP) in the microtube-irrigated ablation catheter group was significantly lower than that in the general ablation catheter group ([81.20 ± 7.15] mmHg vs (87.60 ± 8.17) mmHg, P<0.05). There was a decreased trend in the use of antihypertensive drugs in the microtube-irrigated ablation catheter group as compared with the general ablation catheter group, particularly in the use of diuretics (P<0.05). During the operation, the microtube-irrigated ablation catheter group had a significantly lower catheter temperature (P<0.001), greater energy (P<0.05), and greater decrease in impedance than the general ablation catheter group (P<0.05). No syncope or amaurosis caused by hypotension, or deterioration of renal function occurred in either group. Conclusion: 5 F microtube-irrigated ablation catheter is a safe and effective device during renal artery ablation. It has more advantages than general ablation catheter in reducing SBP and diuretic use in the treatment of resistant hypertension.
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Objective To observe the influence of renal sympathetic denervation (RSD) on renal interstitial fibrosis and transforming growth factor beta 1(TGF-β1) and microRNA-21 (miR-21) in rats with unilateral ureteral obstruction(UUO).Methods 40 male Wistar rats were randomly divided into UUO group (A group,n=10),sham UUO group (B group,n=10),RSD+UUO group (C group,n=1O) and RSD + sham UUO group (D group,n=10).Rats in A group and C group underwent unilateral ureteral ligation,while those in B group and D group underwent sham operation.Rats in C group and D group were followed by RSD.Rats were sacrificed at 21 days after the operation to evaluate the fibrosis by Masson staining.Immunohistochemical staining and Western blotting were used to detect the expressions of collagen I (COL-Ⅰ),collagen Ⅲ (COL-Ⅲ) and TGF-β1 in four groups.The expression of miR-21 was detected by fluorescence in situ hybridization (FISH) and quantitative real-time PCR (RT-qPCR).Results A large amount of collagen deposition was observed in the renal interstitial area in A and C group compared to either B or D group (P ＜ 0.05),but the change in C group was decreased significantly than that in A group (P ＜ 0.05).Similarly,the expressions of COL-Ⅰ,COL-Ⅲ,TGF-β1and miR-21 were obviously higher in A and C group compared to either B or D group (P ＜ 0.05),but those change in C group were decreased significantly than those in A group (P ＜ 0.05).The above indexes were not significantly different between B group and D group (P ＞ 0.05).Conclusion RSD may relieve the renal interstitial fibrosis in UUO rats,and down-regulate the expression of TGF-β1 and miR-21.
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Objective To evaluate the effectiveness of renal sympathetic denervation (RDN) for hypertensive heart dis-ease combined with systolic heart failure. Methods Two patients (mean age 35 years) with hypertensive heart disease com-bined with systolic heart failure on maximal tolerated heart failure therapy underwent bilateral renal denervation. Echocar-diography, the six minute walk distance, renal function, glycosylated hemoglobin and NT-proBNP were assessed at baseline and 1 year after renal denervation. Results Renal artery angiography showed that no stenosis and dissection. After 1 year follow up, the left ventricular ejection fraction (LVEF), six minute walk distance and NT-proBNP were significantly im-proved, and the size of left ventricular decreased. Conclusion RDN is effective and feasible for the treatment in patients with hypertensive heart disease and systolic heart failure.
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Objective To explore the feasibility of the catheter-based renal sympathetic denervation (RDN) guided by monitoring fractional flow reserve (FFR) with pressure guide wire. Methods Eleven minipigs were allocated into RDN group (n=8) and sham operation group (n=3). Before ablation, the angiography of bilateral renal arteries was conducted. Ablation catheter and FFR pressure guide wire were implanted in the renal arteries guided by 7F guided catheter. Then renal arteries were observed by X-ray. The FFR value (renal artery pressure/aortic pressure) was monitored by electric stimulation (20 Hz). When the FFR value had significant change, the target was to be ablated (50°C, 10 W, 60 s). The ablation was considered effective once there was no change of the above indicators after a second stimulation immediately following ablation. Results Renal artery ablation was successfully completed in all the 8 pigs of RDN group. FFR values were monitored before and after ablation, and the results showed that the FFR values were significantly decreased upon stimulation before RDN (0.73±0.07 vs 0.98±0.02, P<0.01), and the FFR values were almost unchanged immediately after ablation (0.97±0.03 vs 0.95±0.02,P=0.25), which was not observed in the sham operation group. Conclusion There is significant difference in the FFR values of the target following stimulation before and after RDN. The FFR pressure guide wire-mediated target ablation may become a new operation mode, with its effectiveness and mechanism needed to be further verified.
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Objective To explore the safety and efficacy of the renal sympathetic denervation under the guidance of EnSite-NavX three-dimensional mapping system. Methods A three-dimensional model of abdominal aorta and renal artery was constructed under the guidance of EnSite-NavX three-dimensional mapping in 6 healthy Guangxi Bama mini-pigs. Then a radiofrequency ablation catheter was put into the bilateral main trunks of renal artery and six points were marked within each trunk from far to near the heart. One side of the renal artery was ablated and the other received no ablation serving as control. The mini-pigs were followed up for 6 months after the procedure. The norepinephrine (NE) content in the renal tissues was detected by ELISA. Sympathetic nerve damage in the renal tissue of the ablation side was observed by Haematoxylin-Eosin staining. Results Modeling and unilateral renal sympathetic denervation were successfully performed in the six mini-pigs. Subcutaneous hematoma was formed after operation in one pig. None of the pigs had the complications such as renal artery stenosis, thrombopoiesis, or dissection. The NE content of ablation side was significantly lower than that of the opposite side ([170.13±52.60] ng/g vs [429.86±131.43] ng/g, P<0.05). Haematoxylin-Eosin staining showed broken epineurium and loss of axons in the renal sympathetic nerve of the ablation side. Conclusion A three-dimensional model of abdominal aorta and renal artery can be clearly constructed under the guidance of EnSite-NavX three-dimensional mapping. Renal sympathetic denervation can be achieved safely and effectively without fluoroscopy or renal arteriography under the navigation of NavX.
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BACKGROUND: Atrial fibrillation (AF) commonly occurs in association with chronic kidney disease (CKD), resulting in adverse outcomes. Combining pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may reduce the recurrence of AF in patients with CKD and hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. Our goal was to compare the impact of PVI + RSD with that of PVI alone in patients with concurrent AF and CKD. METHODS: This was a single-center, prospective, longitudinal, randomized, double-blind study. Forty-five patients with controlled hypertension, symptomatic paroxysmal AF and/or persistent AF, stage 2 or 3 CKD, and a dual-chamber pacemaker were enrolled from January 2014 to January 2015. We assessed the 30-second recurrence of AF recorded by the pacemaker, 24-hour ambulatory blood pressure measurements, estimated glomerular filtration rate, albuminuria, echocardiographic parameters, and safety of RSD. RESULTS: No patient developed procedural or other complications. The ambulatory blood pressure measurements did not differ within the PVI + RSD group or between the PVI + RSD and PVI groups throughout the study. Significantly more patients in the PVI + RSD group than in the PVI group were free of AF at the 12-month follow-up evaluation. The PVI group had an unacceptable response to ablation with respect to changes in echocardiographic parameters, whereas these parameters improved in the PVI + RSD group. CONCLUSION: PVI + RSD were associated with a lower AF recurrence rate than PVI alone; it also improved renal function and some echocardiographic parameters. These encouraging data will serve as baseline information for further long-term studies on larger patient populations.
Subject(s)
Humans , Albuminuria , Atrial Fibrillation , Blood Pressure , Double-Blind Method , Echocardiography , Follow-Up Studies , Glomerular Filtration Rate , Hypertension , Prospective Studies , Pulmonary Veins , Recurrence , Renal Insufficiency, Chronic , SympathectomyABSTRACT
The effectiveness and safety of renal denervation for treating resistant hypertension have been demonstrated by previous studies; meanwhile its potential therapeutic role for chronic kidney disease has also been indicated. Recent clinical and animal studies have confirmed that renal denervation did not cause further damage to renal function of patients with chronic kidney disease; conversely, it may have potential benefits for the patients. In this paper, we reviewed the application and effect of renal denervation in chronic kidney disease.
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Objective To explore the renal artery diameter immediately after the renal sympathetic denervation (RDN) in patients with resistant hypertension. Methods Patients with resistant hypertension were enrolled in this study, and all patients were measured and recorded for the renal artery diameter values using the quantitative coronary angiography (QCA) before and immediately after the RDN. All the ablation parameters including starting impedance, terminal impedance, ablation power, and ablation point were recorded. Ambulatory blood pressure (BP) measurement was performed at the baseline and 6 months after RDN. Results A total of 12 patients with resistant hypertension were finally enrolled in this study. The mean ambulatory BP of the patients was (185±15)/(99±9) mmHg (1 mmHg=0.133 kPa) at admission, which was decreased by 31/15 mmHg in 6 months after RDN, showing significant difference compared with before RDN (P 0.05). No peripheral vascular complications occurred in these patients. Conclusion RDN can significantly reduce the ambulatory BP in patients with resistant hypertension, and expand the renal artery diameter immediately. The degree of renal artery diameter dilation is positively correlated with the ablation impedance decrease, but it can not predict the long-term BP in patients.
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Objective To explore the effect of renal sympathetic denervation (RDN) on cardiac remodeling in myocardial infarction (MI) rats and to investigate the related mechanism. Methods MI rats were induced by ligation of the anterior descending coronary artery. A total of 30 Wistar rats were randomly assigned to MI group (n = 10), MI + RDN group (rats with RDN one weekafter MI, n = 10), and Sham group (n = 10). Four weeks after modeling, the left ventricular cardiac remodeling and function of ratswere examined by echocardiography; the cardiac tissues in the infarct border zone were stained with Masson trichrome for fibrotic analysis. Protein expressions of collagen I, collagens H and transforming growth factor (TGF-(3i) were evaluated by immunohistochemistry. Results Compared with the MI group, the MI + RDN group had significantly increased ejection fraction (EF) and fractional shortening (FS) and significantly decreased left ventricular internal dimensions at end systole and end diastole (all P<0. 05). The results of Masson staining showed that RDN after MI attenuated the collagen deposition around the border area of the infarct region. RDN treatment also inhibited the protein expression of collagen I, H and TGF-β1 in the border area of MI rats (P<0. 05). Conclusion RDN treatment can attenuate cardiac remodeling and improve lett ventricular function after MI, which might be associated with the inhibition of myocardial TGFβ1 expression and the subsequent suppression of collagen deposition.
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Percutaneous catheter-based therapy has recently been introduced to decrease blood pressure by ablation of efferent and afferent sympathetic renal nerves. The patient described here had a seven-year history of hypertension and presented with poorly controlled blood pressure despite antihypertensive therapy with four different drugs. A 44-yr-old man underwent percutaneous renal denervation under local anesthesia using an ablation catheter. After six months of follow-up his blood pressure had dropped 49/37 mmHg with a decrease in 24-hr ambulatory BP of 20/18 mmHg. Renal Doppler ultrasound showed no significant stenosis in either renal artery. This is the first case of successful percutaneous renal denervation, which has recently become available in Korea.