Denervation For Treatment Of Hypertension Research Articles

Renal Denervation for Treatment of Hypertension: From High-Level Quality Evidence to Implementation in Clinical Practice

Renal Denervation for Treatment of Hypertension: From High-Level Quality Evidence to Implementation in Clinical Practice

去肾交感神经术治疗高血压的研究进展

去肾交感神经术治疗高血压的研究进展

Renal sympathetic denervation for treatment of hypertension: where are we now in 2019?

Although sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment resistant hypertension, and early clinical studies had produced encouraging results, the first sham-controlled study (SYMPLICITY HTN-3) failed to achieve its primary efficacy endpoint. Lessons learnt from this trial, and the knowledge derived from further animal and autopsy work, have been applied in three recently published sham-controlled trials. These trials - SPYRAL OFF-MED, RADIANCE SOLO and SPYRAL ON-MED - using newer technologies, demonstrate a 5-10 mmHg incremental reduction in ambulatory SBP from RDN against sham-control, in patients with mild-to-moderate hypertension taking 0-3 drugs. These results provide proof of principle of the blood pressure-lowering effect of renal denervation. We now require data on long-term safety and durability of the procedure. Research is needed to identify predictive markers of response as about one-third of individuals do not respond to renal denervation. Hard-outcome data would be welcome but might be difficult to acquire. Individuals with treatment resistance are obvious treatment candidates, but RDN may also potentially benefit those with medication nonadherence and/or intolerance and those unwilling to take pills.

Catheter-based renal denervation for treatment of hypertension

Catheter-based renal denervation for treatment of hypertension

Low-dose sustained-release deoxycorticosterone acetate-induced hypertension in Bama miniature pigs for renal sympathetic nerve denervation

Recently, the effectiveness of renal sympathetic nerve denervation for treatment of hypertension has been doubted after SYMPLICITY HTN-3 trial. An ideal animal model is still unavailable for preclinical study about catheter-based renal sympathetic nerve denervation for treatment of hypertension. Traditional high-dose deoxycorticosterone acetate (DOCA)–induced hypertension pig model has some problems due to extensive end-organ damage. Based on the similarity in the anatomic characteristics of renal artery between pigs and humans, this study was undertaken to establish a low-dose sustained-release DOCA-induced hypertension model in pigs. A total of 14 pigs were subcutaneously implanted with low-dose DOCA in the abdomen and cannulated from the femoral artery for the measurement of blood pressure (BP). Plasma angiotensin I (Ang I), angiotensin II (Ang II), plasma renin activity (PRA), aldosterone (Ald), creatinine, epinephrine, and norepinephrine (NE) were determined before and after treatments. The kidneys were collected and processed for hematoxylin and eosin staining, Masson–Goldner trichromic, and periodic acid Schiff staining. Ten pigs survived for 1 month. Mean BP significantly increased after 2-week treatment (P < .001). The plasma Ang I, Ang II, PRA, and Ald significantly decreased (Ang I: 6.92 ± 6.06 vs. 2.22 ± 3.08, P = .002; Ang II: 768.85 ± 525.8 vs. 213.76 ± 148.63, P = .003; PRA: 1.68 ± 1.67 vs. 0.29 ± 0.39, P = .008; Ald: 0.37 ± 0.12 vs. 0.25 ± 0.09, P < .001), but norepinephrine significantly increased (7.59 ± 4.57 vs. 16.96 ± 10.38, P = .021). Plasma creatinine remained unchanged. Hisotological examination showed mild damage to the kidney. Low-dose sustained-release DOCA is able to induce hypertension in pigs. A femoral catheter is not only helpful for monitoring BP, but can be used to quickly exchange the renal sympathetic nerve denervation equipment.

Renal Denervation for Treatment of Hypertension: a Second Start and New Challenges.

Following the publication of the randomized controlled but open-label trial Symplicity HTN-2, catheter-based renal sympathetic denervation was proposed as a novel treatment for drug-resistant hypertension. Thousands of procedures were routinely performed in Europe, Australia and Asia, and many observational studies were published. A sudden shift from overoptimistic views to radical scepticism occurred later, when the large US randomized sham-controlled trial Symplicity HTN-3 failed to meet its primary blood pressure lowering efficacy endpoint. Experts are divided on the reasons accounting for the large discrepancy between the results of initial studies and those of Symplicity HTN-3. Indeed, the blood pressure lowering effect associated with renal denervation was overestimated in initial trials due to various patient and physician-related biases, whereas it could have been underestimated in Symplicity HTN-3, which was well designed but not rigorously executed. Still, there is a large consensus on the need to further study catheter-based renal denervation in more controlled conditions, with particular emphasis on identification of predictors of blood pressure response. US and European experts have recently issued very similar recommendations on design of upcoming trials, procedural aspects, drug treatment, patient population and inclusion-exclusion criteria. Application of these new standards may represent a second chance for renal denervation to demonstrate--or not--its efficacy and safety in various patient populations. With its highly standardized treatment regimen, the French trial DENERHTN paved the way for this new approach and may inspire upcoming studies testing novel renal denervation systems in different populations.

Catheter-based Renal Denervation for Therapy of Hypertension: Is There a Hope for Its Resurgence?

Hypertension (HTN) is the most common chronic cardiovascular disease with increasing prevalence all over the world. Despite the availability of many effective antihypertensive drugs, blood pressure control to target values remains low. Resis tant hypertension is defined as ‘blood pressure above goal in adherent patients despite a triple antihypertensive therapy in maximum or maximum tolerated doses, inclu ding a diuretic, which is found in approximately 8 to 18% of all hyper tensives’. Treatment requires a multimodal therapy concept, including—polypharmacy, lifestyle modification and a systematic identification of secondary causes of HTN or pseudoresistance. Increased activity of the sympathetic nervous system has been identified as main contributor to the develop ment and maintenance of resistant HTN. Catheterbased renal dener vation has been introduced as a minimal invasive option for patients with resistant HTN. However, the clinical evidence in support of renal denervation as an effective inter ventional technique is conflicting. A number of observa tional studies and four randomized, controlled trials (Symplicity HTN-2, Prague 15, RSD-LEIPZIG and DENERHTN) support both safety and efficacy of this new therapy, but some smaller studies and the large, single-blind, randomized, sham-controlled Symplicity HTN-3 trial failed to show superiority of renal denervation when compared to medical therapy alone. The present review aims at providing an overview about catheter-based renal denervation for treatment of HTN.

Baroreflex Stimulation Versus Renal Denervation for Treatment of Hypertension: What Constitutes a Logical Comparison of These Interventions on Atrial Electrophysiology?

The autonomic nervous system is a primary modulator of blood pressure, heart rate and cardiac function, and imbalance of the parasympathetic and sympathetic arms of the autonomic nervous system underlies many forms of cardiovascular pathophysiology1. Heart failure and hypertension are often characterized by an excess of sympathetic nerve activity and elevated plasma catecholamine levels. Elevated catecholamines promote activation of the renin-aldosterone-angiotensin system (RAAS). Pharmacologic efforts to treat autonomic imbalance have primarily focused on the use of beta-adrenergic receptor blockers and RAAS antagonists.

Renal Sympathetic Denervation for Treatment of Hypertension.

OPINION STATEMENT: 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.

4. Catheter-based Renal Sympathetic Denervation for Treatment of Hypertension.

4. Catheter-based Renal Sympathetic Denervation for Treatment of Hypertension.