Comparison of standard renal denervation procedure versus novel distal and branch vessel procedure with brachial arterial access

Objectives

We assessed a novel approach to percutaneous renal denervation for uncontrolled hypertension consisting of ablation beyond the proximal main renal artery (Y-pattern), including the primary branches, and compared it to the standard procedure applied only within the main vessel. We also assessed the safety and practicality of a brachial access approach.

Renal denervation in a patient with prior renal artery stenting

This is a case report of a 69‐year‐old female with treatment‐resistant severe arterial hypertension despite prior successful percutaneous intervention to both renal arteries for significant renal artery stenoses (stenting of the right and balloon angioplasty of the left renal artery). The office blood pressure was 221/108 mm Hg at baseline. Secondary hypertension was ruled out and catheter‐based renal denervation performed (distal to the stent in the right renal artery and in the usual fashion in the left renal artery) without complications. The office blood pressure decreased at 1‐ and 3‐month follow‐up to 185/93 mm Hg and 182/95 mm Hg, respectively. This case illustrates the feasibility and potential efficacy of catheter‐based renal denervation in patients with a renal artery stent, an important finding as persistent hypertension is common in patients despite successful renal artery stenting and currently available trials examining renal denervation have excluded patients with prior renal artery stents. © 2012 Wiley Periodicals, Inc.     

Renal artery denervation for treating refractory hypertension

Arterial hypertension is a major healthcare issue affecting between 30 and 40% of the adult population in industrialized countries. Despite the availability of numerous pharmaceutical treatments, arterial hypertension often remains uncontrolled. A non-negligible percentage of patients are refractory to multiple-drug therapy, which exposes them to an increased risk of cardiovascular events. Percutaneous, renal denervation using a catheter connected to a low energy radiofrequency generator has proven effective in decreasing arterial pressure in patients resistant to medical therapy, by reducing afferent nerve activity. In order to be eligible for this therapeutic approach, patients must have uncontrolled essential hypertension despite treatment with a combination of three anti-hypertensive drugs including a diuretic agent, and ≥ 45 mL/min glomerular filtration rate. The initial registry study demonstrated that catheter-based sympathetic renal denervation was a simple and safe procedure resulting in a significant and durable reduction in arterial pressure. Subsequently, a randomized controlled trial (the Symplicity HTN-2 trial) showed a mean 32/12 mmHg decrease in blood pressure measurements in the group of patients who underwent renal denervation whereas no difference was observed in the control group. The reduction in blood pressure was still present at 24-month follow-up. No procedure-related complications were reported and no instances of renal artery stenosis or aneurysmal dilatation were evidenced during the follow-up period. No cases of renal function impairment or deterioration were recorded. This technique seems to be a promising strategy in patients suffering from this serious condition. In order to demonstrate the actual benefit of this technique, we report the case of two patients who underwent renal denervation in our institution.     

Technical and safety aspects of renal denervation

AimsRenal denervation is a novel method used to treat patients with resistant hypertension. Several studies showing the efficacy of this method in blood pressure reduction have been published. However, there is a lack of data that focused on the technical aspects of the procedure. The aim of this paper is to present and discuss the technical and safety issues of the procedure.Methods and results37 patients underwent renal denervation using a Symplicity catheter between 10/2011 and 8/2013. Number of ablations, procedural time, consumption of contrast agent and complication rate during hospitalization were recorded. Bilateral denervation was performed on 35 patients; in 29 of the cases, at least 4 ablations in each renal artery were done. The average duration of procedure was 57 ± 10 min and the average amount of contrast agent used was 93 ± 29 ml. During the study, both values were trending downward as the numbers of procedures increased. We observed minor complications in 9 patients. None of them were serious and none resulted in patient disability.ConclusionRenal denervation is for skilled interventional cardiologist an easy and safe method with a short learning curve. It may be accompanied by minor complications, not deteriorating patient health status.     

Symplicity-3 hypertension trial:Basic and clinical insights

Symplicity-3 hypertension(HTN) was a recently completed clinical trial that was assumed to be the basis for the approved use of renal artery denervation for the treatment of resistant hypertension in the United States.Dramatic reductions in blood pressure had been reported in two clinical trials(Symplicity-1HTN,-2HTN) carried out in Europe,however Symplicity-3HTN did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 mo after renal artery denervation as compared with a sham control.(Denervation group,blood pressure reduction:-14 ± 24,Sham control:-12 ± 26 mm Hg).In this review we discuss several potential explanations for the failure of efficacy of Symplicity-3HTN taking into account basic and clinical factors which could have played a role in the discrepancy between the European and American experience.     

Intra-aortic oxygen distribution during veno-arterial bypass (VAB) without oxygenation in circulatory assist

Right atrium-femoral artery VAB without oxygenation was performed in 7 dogs at 3 different bypass ratios, 15% 30%, and 45%. Respiration and cardiac output were controlled. Precise intra-aortic distributions of PO2 and O2 saturation were determined by means of a PO2 catheter probe and an oxygen analyzer. The following was concluded: 1) The blood pumped from dog heart produced a narrow "mixing zone" in the mid-aorta with the blood pumped from VAB. The area of the "mixing zone" was in the distal half between renal artery and bifurcation at 15% bypass ratio, in the proximal half between renal artery and bifurcation at 30% bypass ratio, and from celiac artery to below renal artery at 45% bypass ratio. It shifted proximally as the bypass ratio increased. 2) In order to supply necessary oxygen to abdominal viscera, it is recommended that the bypass flow should not exceed 30% of the baseline cardiac output.     

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.     

Les sténoses artérielles rénales post-dénervation – une problématique préoccupante ?

Renal denervation, an invasive technique indicated in resistant hypertension patients insufficiently controlled by antihypertensive drugs, has a good safety profile. However, an increasing number of post-denervation renal artery stenosis cases has recently been reported. We describe the case of a 49-year-old woman with resistant hypertension who was referred to our university hypertension center for renal sympathetic denervation. Her daily treatment included six antihypertensive drugs. CT angiography prior to denervation showed no renal artery stenosis or vessel wall lesions. A standard renal denervation procedure using the St Jude protocol was performed. After an initial improvement in blood pressure profile, she presented with a blood pressure impairment at 3 months after renal denervation leading to the diagnosis of a severe right renal artery stenosis.     

Interventionelle Therapiestrategien bei resistenter Hypertonie

For some years it has been possible to offer two new interventional treatment options to patients with resistant hypertension, stimulation of the carotid baroreceptors and radiofrequency ablation of the activated renal sympathetic nerve (renal denervation). With the first method the baroreceptors in the carotid sinus are stimulated after prior implantation of electrodes and a programmable pulse generator system. In the second method the renal sympathetic nerve fibers of the renal arteries are severed by minimally invasive catheter-aided radiofrequency ablation. Both therapy options achieve a systolic blood pressure reduction of at least 10?mmHg in 70?C90% of patients. With carotid sinus stimulation the average blood pressure was reduced on average by approximately 30?C35/15?C20?mmHg 12 months after implantation. Comparable data but with a slightly less pronounced tendency, have been published for renal denervation. Contraindications for carotid sinus stimulation are carotid stenosis of more than 50% or large carotid plaques and for radiofrequency ablation of renal sympathetic activity renal artery stenosis or a history of renal artery stenting and additionally patients with an estimated glomerular filtration rate (eGFR) under 45?ml/min.     

La dénervation rénale un traitement pour l’hypertension artérielle résistante : expérience française

Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in “Real World” clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP > 160 mmHg despite treatment with ≥ 3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFR < 45 mL/min). The basal BP (home or ambulatory) was 179.1 ± 20.75/99.66 ± 19.76 mmHg, despite an average of 4.91 ± 0.98 medications per patient. Successful bilateral sympathetic denervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (P < 0.01). At 2 years follow-up, systolic blood pressure (ABPM or Home BP) was 143.8 ± 15.30 mmHg (P < 0.0001) and diastolic 83.42 ± 12.80 mmHg (P = 0.0004). There were no adverse events during follow-up, and no deterioration in renal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations.     

Retardation of the development of hypertension in DOCA-salt rats by renal denervation

To determine the importance of the renal nerves in DOCA-salt hypertension, either renal denervation or a sham-operation was carried out on both DOCA-salt-treated and non-DOCA-treated rats. The systolic blood pressure of the non-DOCA rats remained within normotensive levels, in which the difference in blood pressure levels between the renal denervated and the sham-operated groups was not significant. On the other hand, the blood pressure of the rats treated with DOCA, and having intact renal nerves, began to rise by the end of the first week and rose consistently thereafter, whereas, in the renal denervated DOCA-salt rats, the blood pressure started to rise by the second week and then proceeded to increase gradually. The differences between the sham and the denervated rat groups were significant throughout the four weeks. The mean arterial pressure, directly measured from the caudal artery of conscious rats during the fourth week of this study, was 166 +/- 7 mmHg in the sham-operated and 129 +/- 4 mmHg in the renal-denervated rats (the data having an 1% significant difference). To test the effects of renal denervation on the natriuresis, pentobarbital-anesthetized rats were infused intravenously with physiological saline. The renal denervated rats which had received DOCA excreted more sodium than did the sham-operated rats. When the rats were later anesthetized with urethane to allow intracisternal injections of hypertonic saline, the mean blood pressure in renal denervated rat groups was again lower than that of the sham-denervated rat groups. However, subsequent intracisternal injections of 5% saline produced similar pressor responses as well as tachycardia in both DOCA groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sténose de l’artère rénale à distance d’une dénervation rénale pour HTA résistante

The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis.     

Renal Denervation Using an Irrigated Catheter in Patients with Resistant Hypertension: A Promising Strategy?

Background

Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension.

Objective

To evaluate the feasibility and safety of renal denervation using an irrigated catheter.

Methods

Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months.

Results

The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed.

Conclusion

Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings.     

Regional wave travel and reflections along the human aorta: a study with six simultaneous micromanometric pressures

The human aorta and its terminal branches were investigated in normal subjects during elective cardiac catheterization to evaluate regional wave travel and arterial wave reflections. A specially designed catheter with six micromanometers equally spaced at 10 cm intervals was positioned with the tip sensor in the distal external iliac artery and the proximal sensor in the aortic arch. Simultaneous pressures were obtained and analyzed for foot-to-foot wave velocity, and Fourier analysis was used to derive apparent phase velocity. These quantities were assessed during control (n = 9), during Valsalva (n = 8) and Müller (n = 4) maneuvers, and during femoral artery occlusion by bilateral manual compression (n = 8). During control, regional cross-sectional areas, determined from aortography, and regional foot-to-foot pulse wave velocities were used to calculate the local reflection coefficient in the proximal descending aorta (gamma = 0.05), at the junction of the renal arteries (gamma = 0.43), and at the terminal aortic bifurcation (gamma = 0.13). To test the hypothesis that significant reflections originate in the aorta, at the level of the renal arteries, aortograms were used to design a latex tube model with geometric properties similar to the descending aorta. Velocities and reflection characteristics in the model and in vivo were compared. Inspection of thoracic aortic pressures under control conditions revealed a reflected wave originating from the region of the aorta at the level of the renal arterial branches while abdominal pressures exhibited reflection from a site peripheral to the terminal aortic bifurcation. In the low frequency range, apparent phase velocity was found to be higher proximal to the renal arteries as compared with at the distal sites. In addition, the minimum value occurred at a higher frequency in the lower thoracic aorta than at more distal sites. The effects of reflection on apparent wave velocity in the tube model were consistent with data obtained in vivo. The Valsalva maneuver diminished the reflection from the aortic region of the renal arteries, thus allowing the distal reflected wave to become more evident on the thoracic pressure waveforms. Bilateral femoral artery occlusion usually enhanced the distal reflection and the Müller maneuver usually resulted in small increases in reflections. In conclusion, the geometric and elastic nonuniformity of the aorta results in two major sites of arterial wave reflection that influence the aortic pressure waveforms in man.(ABSTRACT TRUNCATED AT 400 WORDS)     

Noninvasively and invasively measured pulsatile haemodynamics with graded arterial stenosis.

Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respectively. Pulsatile blood pressure was measured 0.6 cm proximal and 3.7 cm distal to the stenosis. With increasing severity of stenosis there were progressive increases in the femoral artery hydraulic input impedance moduli and in the ratio of the impedance moduli to the zero harmonic impedance (or total resistance). This resulted in: a) a progressive reduction in the Fourier harmonic moduli and pulsewave amplitudes of flow, velocity, and distal pressure; b) a progressive increase in the fifth-seventh proximal pressure harmonic moduli; but c) little change in mean proximal pressure or its first 4 harmonic moduli. The data confirm the well known phenomena of a 'critical stenosis' in that there is little decrease in resting mean blood flow until there is a 70 to 80 stenosis (area reduction). Also the oscillatory portions of the femoral artery data were more sensitive to the changes in stenosis than were the nonoscillatory parameters, which confirms previously reported findings from the thoracic aorta. However, the femoral artery haemodynamics exhibited a greater amount of frequency dependent behaviour than the thoracic aorta which is probably the result of a more complex interaction of reflections from the stenosis and from the periphery in the femoral artery than in the thoracic aorta. The sensitive changes in oscillatory haemodynamics may provide a useful basis for noninvasive and invasive physiological assessment of human peripheral atherosclerotic stenosis and of experimental stenosis in animals.     

The Role of Renal Sympathetic Nerves in Hypertension: Has Percutaneous Renal Denervation Refocused Attention on Their Clinical Significance?

Renal sympathetic efferent and afferent nerves, which lie within and immediately adjacent to the wall of the renal artery, contribute to the pathogenesis of hypertension. Because the causative factors of hypertension change over time, denervation of both efferent and afferent nerves should result in long-term attenuation of the hypertension. The importance of the renal nerves in patients with hypertension can now be defined with the novel development of percutaneous minimally invasive renal denervation from within the renal artery using radiofrequency energy as a therapeutic strategy. Studies thus far show that catheter-based renal denervation in patients with refractory hypertension lowers systolic blood pressure 27 mm Hg by 12 months with estimated glomerular filtration rate remaining stable. An attenuation of hypertension of this magnitude by catheter-based renal sympathetic denervation in combination with pharmacologic therapy is likely to be valuable in decreasing the risks of stroke, left ventricular hypertrophy, heart failure, and chronic renal failure.     

The effect of chronic constriction of the aorta on arterial blood pressure in dogs: An attempt to produce coarctation of the aorta

The aortae of dogs may be constricted or occluded at the arch without the development of arterial hypertension proximal to the occlusion. Hypotension of moderate to marked degree occurs distal to the occlusion, and is usually more marked a few hours after clamping than later. the return toward normal of the pressure distal to the clamp was attributed, among other causes, chiefly to the development of collateral circulation and acute and chronic thining of the vessel walls within the clamp. After several days the pressure in the femoral artery may fall progressively, without simultaneous reduction of carotid pressure. The oxygen content of the blood does not appear to be reduced significantly until a great reduction of femoral pressure has occurred.The failure to produce, in dogs, hypertension proximal to a clamp constricting the aorta at or near the site where aortic coarctation occurs in human beings is attributed to the ready development in dogs of an extensive collateral circulation.Hypertension of renal origin occurs when the aorta is closed a few centimeters below the origin of the renal vessels, and, in addition, constricted or closed in the thorax at a level corresponding to the dome of the diaphragm. Removal of the kidneys reduces or abolishes this hypertension. The hemodynamic changes are sufficiently similar to suggest the possibility that the hypertension of human coarctation is of renal origin, and that the manner in which collateral circulation develops differentiates the response to constriction of the aorta in dogs and men.     

Comparison of office and serial automatic blood pressure readings in renovascular and essential hypertension.

Office blood pressures were compared with those obtained using a thirty minute recording with an automatic device (Dinamap) in thirty patients with essential hypertension and nineteen subjects with hypertension and renal artery stenosis. When matched for age and sex, no differences were found between both groups of patients with respect to their office or automatically recorded blood pressures. The difference between office and automatically assessed systolic blood pressures was similar in both groups. The difference in diastolic pressures was slightly larger in the group with renal artery stenosis. The number of patients showing a pressure drop greater than 10 mm Hg was comparable in the two groups. We conclude that blood pressure levels obtained in the office overestimate 'true' blood pressure not only in essential but also in renovascular hypertension.     

Effect of denervation on the afferent arteriole in the SHR

To study the role the renal nerves may play in the hypertension of the SHR, we conducted a morphometric study of the afferent arteriole of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) which were subjected to renal denervation (or sham-operation). Methacrylate casts were made of the renal vasculature after perfusion fixation with glutaraldehyde. These vascular casts were then examined and measurements made with the scanning electron microscope (SEM). Afferent arterioles of the denervated SHR were dilated in comparison to the sham-operated SHR, but there was no difference between the afferent arteriolar diameters of the 2 groups of WKYs. However, the afferent arteriolar diameters of the SHR (either group) were smaller than those of the WKY. Renal denervation caused a reduction in systolic blood pressure compared to sham-operated in both strains of rat. We concluded that the dilation changes of afferent arterioles of denervated SHRs may be related to renal autoregulation resulting from the decreased blood pressure. However, the effect of the loss of sympathetic innervation of the arterioles cannot be ruled out.     

A comparison of proximal and distal high-frequency jet ventilation in an experimental animal model

High-frequency jet ventilation using either a proximal or a distal endotracheal injection site through a triple-lumen endotracheal tube was studied in 10 adult cats. The comparative effects on pulmonary gas exchange, tracheal pressure, heart rate, and blood pressure were examined for each injection site at both high (8-12 pounds per square inch [PSI] and low (5-8 PSI) jet-driving pressures in normal and lung-injured cats. Lung injury was created by modification of a surfactant washout technique previously demonstrated in rabbits. Alveolar ventilation (PaCO2) was found to be significantly better with distal than with proximal jet injection under all experimental conditions. At high jet-driving pressures, peak inspiratory pressure was higher in both normal (p = 0.03) and lung-injured cats (p = 0.002) with distal high-frequency jet ventilation. In addition, lung-injured animals were observed to have higher distal mean airway pressures at high jet-driving pressures (p less than 0.01). No differences in oxygenation were found in any circumstances. The results of this animal study suggest that distal high-frequency jet ventilation may be more effective in those situations in which improvement in alveolar ventilation is the major goal and that during proximal high-frequency jet ventilation airway pressures should be monitored as far distally as possible.