肾交感神经阻断术治疗难治性高血压

交感神经的普遍激活是高血压病发病机制的重要环节,并参与难治性高血压的维持。外科交感神经切除术大大提高了难治性高血压的存活率,显示了良好的降压效果;但由于手术风险及严重术后并发症而被降压药物所代替。肾交感神经阻断术是一种新的非药物治疗方法,有损伤小、恢复快、无全身不良反应的优点,再次点燃了抑制交感神经治疗高血压病的希望。     

Renal Sympathetic Denervation for Resistant Hypertension

Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin–angiotensin II–aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled.     

Renal Sympathetic Denervation for Treatment of Resistant Hypertension: A Systematic Review

Catheter‐based renal sympathetic denervation (RSD) is a novel technique that is being investigated as treatment for resistant hypertension. To systematically evaluate the existing literature on the safety and efficacy of RSD in persons with resistant hypertension, online searches of Medline and the Cochrane Library Database (up to June 2012) were performed. Randomized controlled trials, observational studies, and conference proceedings published in English language were included. Nineteen studies (N=683 persons) were included. Follow‐up duration ranged from 1 to 24 months. All studies reported significant reductions in systolic and diastolic pressures. Maximal reduction of blood pressure ranged from 18 mm Hg to 36 mm Hg (systolic) and 9 mm Hg to 15 mm Hg (diastolic). Sustained benefit of blood pressure reduction at 12 months was seen in 5 studies. No worsening of renal function was reported and there were few procedure‐related adverse events such as pseudoaneurysm formation, hypotension, and bradycardia. Data from short‐term studies suggest that RSD is a safe and effective therapeutic option in carefully selected patients with resistant hypertension. Long‐term studies with large patient populations are needed to study whether this benefit is sustained with a demonstrable difference in cardiovascular disease event rates.     

Renal Sympathetic Denervation for Treatment of Hypertension

Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure.     

Renal Sympathetic Denervation for Resistant Hypertension Treatment - Current Perspectives

The authors review the concept of resistant hypertension and the involvement of the sympathetic nervous system in hypertension as a rational basis for the technique of renal sympathetic denervation (RSD) performed percutaneously. This revision is the result of an active search for scientific articles with the term "renal denervation" in the Medline and PubMed databases. The techniques and devices used in the procedure are presented, as well as clinical outcomes at six, 12 and 24 months after the intervention with the Symplicity catheter. Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal. New devices for RSD and its ongoing clinical studies are cited. In conclusion, the RSD presents itself as an effective and safe approach to resistant hypertension. Results from ongoing studies and longer follow-up of these patients are expected to confirm the initial results and put into perspective the expansion of the procedure use in hypertension approach.     

Renal Sympathetic Denervation: Early Impact on Ambulatory Resistant Hypertension

Although guidelines recommend ambulatory blood pressure (BP) monitoring (ABPM), few data are available regarding the effects of renal denervation (RDN) on 24‐hour ABPM values. A total of 44 patients with mean systolic BP ≥135 mm Hg on ABPM despite adequate therapy were included. Basal systolic BP (SBP) and diastolic BP (DBP) were 154±11 mm Hg and 86±12 mm Hg, respectively. At 1 month, SBP and DBP were reduced to 146±18 mm Hg (P=.01) and 82±14 mm Hg and showed no further decrease up to 6 months. Only 55% of the patients responded to RDN (≥−5 mm Hg SBP), with a mean responder rate drop of 21/11 mm Hg. Neither the number of ablation points nor the amount of impedance drop was predictive of response. Only approximately half of patients with resistant hypertension responded to RDN. However, in these responders, a remarkable reduction of 24‐hour BP occurred as early as 1 month after RDN.

Hypertension is a major cardiovascular (CV) risk factor affecting one quarter of the adult population in Western societies.¹ Up to 12% of patients have resistant hypertension, defined as uncontrolled systolic blood pressure (SBP) despite therapy with ≥3 different antihypertensive agents, including a diuretic.², ³ Until now, surgical sympathectomy has been reported to significantly reduce blood pressure (BP) in resistant hypertension; however, perioperative morbidity was high.⁴, ⁵ By showing that percutaneous endovascular renal denervation (RDN) could represent a safe and effective alternative, the Symplicity HTN‐1 and HTN‐2 trials for resistant hypertension recently renewed interest in sympathectomy.⁶, ⁷ The proof‐of‐concept study with the Simplicity catheter has led to a series of trials—recently also conducted with improved catheter systems—to investigate the effects of this invasive approach.⁸, ⁹, ¹⁰, ¹¹ All studies consistently determined reductions in systolic and diastolic office BP values.⁸, ⁹, ¹⁰, ¹¹, ¹², ¹³ In addition, beneficial impact on sleep apnea, glucose intolerance, heart function, renal function, and rhythm disorders have been reported.¹⁴, ¹⁵, ¹⁶, ¹⁷ Until now, few data have become available with regard to the effects of RDN on resistant hypertension as verified in ambulatory BP monitoring (ABPM)⁸, ¹³, ¹⁸, ¹⁹, ²⁰the procedure recommended by guidelines and the literature for accurate evaluation of hypertension and for exclusion of pseudoresistance.²¹, ²² It has been clearly demonstrated that ABPM avoids overestimation and underestimation of BP and is also associated with risk prediction for CV events.²³, ²⁴, ²⁵ In the present study, we analyzed the effect of RDN on 24‐hour ABPM values up to a follow‐up of 6 months for better appraisal of BP changes.     

肾脏交感神经消融术治疗顽固性高血压的研究进展

原发性高血压是人数最多的心血管疾病之一。现在普遍认为,其发病机制是多因素的,因此治疗方法也应该针对病理生理的多个方面。目前,尽管多种抗高血压药物联合的治疗策略取得了良好的临床效果,但仍有部分顽固性高血压的患者无法达到目标血压。近年来,基于充分的动物实验研究和受惠于医疗器械技术的进步,一种新的使用射频导管通过微创介入途径有选择性地破坏肾交感神经从而降低血压的方法脱颖而出。在此,我们对这项技术的理论基础,临床试验结果以及发展趋势进行简单探讨。     

Resistant Hypertension and Renal Nerve Denervation

Patients with resistant hypertension are a subgroup of the hypertensive population that are at even greater risk of cardiovascular outcomes. Therapeutic options for these patients are limited to antihypertensive medications. However, renal denervation (RDN) is a novel nonpharmacologic intervention that involves a catheter-based ablation of the sympathetic nerves within the renal artery wall. The procedure initially showed promise with remarkable blood pressure reductions until the pivotal SYMPLICITY HTN-3 trial failed to demonstrate superiority of RDN over control. This trial was notable for a substantial placebo effect and an attenuated response to RDN. These findings, which contradicted those of prior studies, have raised numerous questions, including whether adequate RDN occurred in those patients. Further research is planned to resolve some of these questions and to clarify the role of RDN in treating patients with resistant hypertension.     

Unilateral Catheter-based Renal Sympathetic Denervation in Resistant Arterial Hypertension Shows No Blood Pressure-lowering Effect

A 68-year-old woman with resistant essential arterial hypertension despite the regular use of four antihypertensive drugs was referred to the catheter-based renal sympathetic denervation. Due to the complicated anatomy, insertion of the guiding catheter into the left renal artery was not stable. Thus, renal denervation of only the right renal artery was performed. Before and after renal denervation, the patient’s blood pressure was monitored by home blood pressure (BP) telemonitoring. The average 7-day home BP telemonitoring values before and 1, 2, and 3 months after denervation were 187.1/124.1, 193.3/123.1, 198.3/129.6, and 195.2/128.0 mm Hg. After unilateral renal denervation, no BP decrease occurred. This unique case suggests that unilateral catheter-based renal sympathetic denervation in resistant arterial hypertension shows no BP-lowering effect. Therefore, when treating resistant hypertension by catheter-based renal denervation, it seems advisable to try always to perform an effective bilateral procedure.     

交感神经去除术在肺动脉高压治疗中的研究进展

肺动脉高压是一种复杂的临床综合征,虽然在心肺血管疾病中发病率不高,但因其严重影响患者生活质量,致死风险高,被称为心血管疾病中的恶性疾病。靶向药物治疗使得肺动脉高压病情得到一定程度控制,但整体控制率仍不容乐观。随着肺动脉高压相关研究的推进,目前认为交感神经的过度激活在肺动脉高压的发生和维持中起到一定作用,且基于调节自主神经活性的药物和器械治疗在肺动脉高压中的研究得到了一些发现。现就交感神经在肺动脉高压发生和发展的作用、肺动脉神经分布特点和交感神经活性调节的非药物治疗研究进行综述,以探讨肺动脉高压治疗的新思路。     

The Future of Renal Denervation in Resistant Hypertension

Resistant hypertension, defined as inadequate blood pressure control despite three or more antihypertensive medications at maximally tolerated doses, is strongly linked to increased cardiovascular morbidity and mortality. Increased renal afferent and efferent sympathetic activity carried by nerves which arborize the adventitia of the renal arteries, appears to be central to the pathobiology of resistant hypertension. Historical experience indicates that surgical denervation and/or sympathectomy often dramatically reduced blood pressure in patients with malignant hypertension. Catheter-based radio-frequency renal denervation was developed in the past decade as a percutaneous adaptation of surgical denervation. Percutaneous renal denervation using a variety of systems has demonstrated to date, in non-randomized and unblinded studies, dramatic reductions in office-based blood pressure, but more modest impact on ambulatory blood pressure. The only single, appropriately powered, blinded, sham-controlled study of renal denervation conducted to date, however, failed to meet its primary endpoint, casting doubt on the value of the therapy. Ancillary benefits of renal denervation have been described in such conditions as diabetes mellitus, heart failure, and sleep apnea but require further study. While renal denervation is already widely available outside of the USA for commercial use, its utility in resistant hypertension must be vetted by further rigorous investigation before its use can be routinely recommended.     

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension.MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed.Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation.ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.