Endovascular Therapy: A Game-Changing Treatment for Resistant Hypertension

In the Western world, 30% to 40% of the adult population suffers from hypertension. The prevalence is expected to increase with the aging population. Sixty-five percent of patients over 60 years of age are affected by hypertension, which affects nearly a billion people worldwide. It has been thought to be not only a major risk factor for cardiovascular disease but also probably the greatest risk factor for cardiovascular disease. Hypertension is purported to be responsible for 7 million deaths worldwide, including death from stroke, heart failure and renal failure.¹

Even though resistant hypertension affects only a minor proportion of overall patients with hypertension, it is becoming more and more difficult to control, and the rate of uncontrolled hypertension has risen from 15.9% in 1988 to 1994 to 28% in 2005 to 2008, mirroring the rise in prevalence of obesity.² 

Renal sympathetic efferent and afferent nerves are recognized as critical in the hypertensive disease process and represent an important therapeutic target. From the 1930s to 1950s, investigators performed surgical interruption of the sympathetic pathway and effectively lowered the pressure significantly in patients, but there were complications that precluded the continued application of this technique at the same time that effective drug regimens evolved. 

Recently, renal denervation has been reborn as a catheter technique utilizing the proximity of the renal nerves to the renal arteries utilizing various forms of energy or injections. This technique has been effective in treating high blood pressure in as many as 85% of patients. The ability to perform this transcatheter technique has the potential to be a true game changer in cardiovascular care.³

The excellent review by Rocha-Singh in this issue of Vascular Disease Management entitled “Endovascular Therapy for Treatment of Resistant Hypertension: Emerging Controversies and Technical Evolution,” described the basis and preliminary results of this technique with multiple devices.⁴ Certainly the results are quite heartening with the majority of patients having improvement in their blood pressure control. There are also some additional collateral benefits including an improvement in insulin resistance, sleep apnea, heart failure, and other nonrenal effects. 

Potential Drawbacks

There have been some caveats recently raised that there is a potential harm in RF application in the arterial bed.⁵ In a 32-patient study, renal arteries were evaluated with automatic pullbacks performed before and after renal denervation with optical coherence tomography. There was not only diffuse arterial constriction and local tissue damage but also edema and thrombus formation not apparent by angiography. Whether this has clinical relevance remains to be seen.

With this evolving new treatment we have to raise some more questions. In general this has been applied for patients who have true resistant hypertension. A question could be raised as to why we are only treating compliant patients. Many patients who are noncompliant simply cannot afford the medication or they cannot tolerate the medicines. Also, in third-world countries, it is possible that this might be a cost effective therapy in general. Other questions include the following: Why are we not treating younger patients? Why are we not treating patients with mild hypertension? What about the patients with renal insufficiency? 

Some other caveats need to be raised. Response rates are variable and in the cases of the Symplicity Study, as few as 69% were effectively treated.⁴ The question is, why is there no response immediately and are there ways for us to evaluate who is effectively denervated with the currently applied technology?

There have also been suggestions that efferent nerves can regrow. Whether this has any clinical relevance is unknown because the results so far have been fairly durable. Although the complication rate is low (2.61%), it could be possible to reduce it further.¹ And new technologies could enable providers to perform RDN in an outpatient setting. 

The Verve Medical device is a nonvascular system that exploits the proximity of the renal nerves to the renal pelvis.⁶ In the location of the renal pelvis, both the efferent and afferent nerves are located and intertwined within the multiple layers of the renal pelvic wall. If the clinical experience with the Verve device confirms efficacy, safety, and durability, there is a possibility patients could be treated as an outpatient without utilization of contrast. 

Renal denervation therapy is exciting and may be a true game changer for treating patients with not only hypertension but also renal insufficiency, congestive heart failure, diabetes mellitus, obesity, sleep apnea, and glucose intolerance. This treatment is moving so quickly and has been effective enough in its early stages that the European Society of Cardiology (ESC) has issued a consensus statement saying patients are appropriately to be screened for this therapy if they meet the following criteria:⁷

• Office-based blood pressure is ≥160 mmHg (≥150 mmHg in patients with type II diabetes).
• Use of three or more antihypertensive drugs in adequate dosage and combination, including use of a diuretic.
• Have attempted to modify blood pressure with lifestyle changes.
• Secondary hypertension has been excluded.
• Pseudoresistance has been excluded with the use of ambulatory blood-pressure monitoring.
• Patients have preserved renal function (glomerular filtration rate ≥45mL/min/1.732).

Conclusion

At the time of this publication, five renal denervation catheter systems have received CE Mark approval. There are thought to be at least 60 medical companies involved in this new technology. Other new therapies, including less invasive and outpatient-based therapies may or may not be equally effective. We shall await further data. 

We continue to watch the evolution of this exciting therapy and the article and review by Rocha-Singh opens the doors to those who are perhaps not familiar with this technology to get a flavor of what may be one of the most exciting new therapies in the early part of the 21st century.

Editor’s Note: Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports stock ownership in Verve Medical, Inc. 

Address for correspondence: Richard R. Heuser, MD, FACC, FACP, FESC, FSCAI, St. Luke’s Medical Center, Cardiology, 555 N. 18th Street, Suite 300, Phoenix, AZ 85006, USA. Email: rheuser@iasishealthcare.com  

REFERENCES

1. Polimeni A, Curcio A, Indolfi C. Renal sympathetic denervation for treating resistant hypertension. Circ J. 2013;77(4):857-863.

2. Bunte MC, Infante de Oliveira, E, Shishehbor, MH. Endovascular treatment of resistant and uncontrolled hypertension. JACC Cardiovasc Interv. 2013;6(1):1-9.

3. Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275-1281.

4. Mayeda G, Pliagas G, LeSar C, Julien W, Lew D, Bajaj S. Procedural Outcomes of Orbital Atherectomy Treatment of Peripheral Arterial Disease in an Outpatient Office-Based vs. Hospital Setting. Vasc Dis Manag. In press.

5. Templin C, Jaguszewski M, Ghadri JR. Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity catheter system and the EnligHTN multi-electrode renal denervation catheter. Eur Heart J. 2013 April 25 (Epub ahead of print).

6. Heuser RR, Mhatre AU, Buelna TJ, Berci WL, Hubbard BS. A novel non-vascular system to treat resistant hypertension. EuroIntervention. 2013;9(1):135-139.

7. Mahfoud F. Lüscher TF, Anderson B, et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013; April 25 (Epub ahead of print).