CardioVascular and Interventional Radiology

, Volume 39, Issue 2, pp 251–260 | Cite as

Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

  • J. Ricke
  • M. Seidensticker
  • S. Becker
  • J. Schiefer
  • I. Adamchic
  • K. Lohfink
  • M. Kandulski
  • A. Heller
  • P. R. Mertens
Clinical Investigation

Abstract

Objectives

CT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.

Materials and Methods

Eleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.

Results

No toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).

Conclusion

CT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

Keywords

Therapy-resistant arterial hypertension Sympathetic nerves Vasotonus CT-guided ablation 

Notes

Compliance with Ethical Standards

Conflict of Interest

All authors declare they have no conflict of interest.

Ethical Approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The institutional review board approved the study. All patients provided written informed consent prior to inclusion. The study was registered as EudraCT 2012-002978-31.

Informed Consent

Informed consent was obtained from all individual participants included in this study.

Supplementary material

270_2015_1261_MOESM1_ESM.pdf (77 kb)
Supplementary material 1 (PDF 76 kb)

References

  1. 1.
    Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global Burden of disease study 2010. Lancet. 2012;380:2224–60.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Wolf-Maier K, Cooper RS, Banegas JR, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA. 2003;289:2363–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension. 2011;57:1076–80.CrossRefPubMedGoogle Scholar
  6. 6.
    Norvell JE. The aorticorenal ganglion and its role in renal innervation. J Comp Neurol. 1968;133:101–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Newcombe CP, Shucksmith HS, Suffern WS. Sympathectomy for hypertension; follow-up of 212 patients. Br Med J. 1959;1:142–4.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Esler M, Jennings G, Korner P, et al. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988;11:3–20.CrossRefPubMedGoogle Scholar
  9. 9.
    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;373:1275–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Catheter-based renal sympathetic denervation for resistant hypertension. durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:911–7.CrossRefGoogle Scholar
  11. 11.
    Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (the symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376:1903–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401.CrossRefPubMedGoogle Scholar
  13. 13.
    Azizi M, Sapoval M, Gosse P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015;385:1957–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Jang SH, Ahn SH, Park SM, Kim SH, Lee KH, Lee ZI. Alcohol neurolysis of tibial nerve motor branches to the gastrocnemius muscle to treat ankle spasticity in patients with hemiplegic stroke. Arch Phys Med Rehabil. 2004;85:506–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Rogits B, Jungnickel K, Lowenthal D, et al. Prospective Evaluation of the radiologist’s hand dose in CT-guided interventions. Rofo. 2013;185:1081–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Kambadakone A, Thabet A, Gervais DA, Mueller PR, Arellano RS. CT-guided celiac plexus neurolysis: a review of anatomy, indications, technique, and tips for successful treatment. Radiographics. 2011;31:1599–621.CrossRefPubMedGoogle Scholar
  17. 17.
    Noble M, Gress FG. Techniques and results of neurolysis for chronic pancreatitis and pancreatic cancer pain. Curr Gastroenterol Rep. 2006;8:99–103.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee JM. CT-guided celiac plexus block for intractable abdominal pain. J Korean Med Sci. 2000;15:173–8.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Gress F, Schmitt C, Sherman S, Ikenberry S, Lehman G. A prospective randomized comparison of endoscopic ultrasound- and computed tomography-guided celiac plexus block for managing chronic pancreatitis pain. Am J Gastroenterol. 1999;94:900–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Fujita Y. CT-guided neurolytic splanchnic nerve block with alcohol. Pain. 1993;55:363–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Buy JN, Moss AA, Singler RC. CT guided celiac plexus and splanchnic nerve neurolysis. J Comput Assist Tomogr. 1982;6:315–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Streitparth F, Walter A, Stolzenburg N, et al. MR-guided periarterial ethanol injection for renal sympathetic denervation: a feasibility study in pigs. Cardiovasc Interv Radiol. 2013;36:791–6.CrossRefGoogle Scholar
  23. 23.
    Streitparth F, Gebauer B, Nickel P, et al. Percutaneous computer tomography-guided ethanol sympathicolysis for the treatment of resistant arterial hypertension. Cardiovasc Interv Radiol. 2014;37:513–8.CrossRefGoogle Scholar
  24. 24.
    Firouznia K, Hosseininasab SJ, Amanpour S, Haj-Mirzaian A, Miri R, Muhammadnejad A, Muhammadnejad S, Jalali AH, Ahmadi F, Rokni-Yazdi H. Renal sympathetic denervation by CT-scan-guided periarterial ethanol injection in sheep. Cardiovasc Interv Radiol. 2015;38(4):977–84.CrossRefGoogle Scholar
  25. 25.
    Vonend O, Antoch G, Rump LC, Blondin D. Secondary rise in blood pressure after renal denervation. Lancet. 2012;380:778.CrossRefPubMedGoogle Scholar
  26. 26.
    Kaltenbach B, Id D, Franke JC, et al. Renal artery stenosis after renal sympathetic denervation. J Am Coll Cardiol. 2012;60:2694–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Kandzari DE, Bhatt DL, Sobotka PA, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial. Clin Cardiol. 2012;35:528–35.CrossRefPubMedGoogle Scholar
  28. 28.
    Gelczer RK, Charboneau JW, Hussain S, Brown DL. Complications of percutaneous ethanol ablation. J Ultrasound Med. 1998;17:531–3.PubMedGoogle Scholar
  29. 29.
    May O. The functional and histological effects of intraneural and intraganglionic injections of alcohol. Br Med J. 1912;2:465–70.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Xu RH, Gao W, Wang C, et al. Systematic evaluation of percutaneous radiofrequency ablation versus percutaneous ethanol injection for the treatment of small hepatocellular carcinoma: a meta-analysis. Eur J Med Res. 2014;19:39.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Wang S, Zhuang L, Meng Z. Hepatocellular carcinoma more than 3 cm in diameter: a systematic review of transcatheter arterial chemoembolization plus percutaneous ethanol injection versus transcatheter arterial chemoembolization alone. ISRN Gastroenterol. 2013;2013:526024.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Fischell TA, Vega F, Raju N, et al. Ethanol-mediated perivascular renal sympathetic denervation: preclinical validation of safety and efficacy in a porcine model. EuroIntervention. 2013;9:140–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2015

Authors and Affiliations

  • J. Ricke
    • 1
    • 3
  • M. Seidensticker
    • 1
    • 3
  • S. Becker
    • 1
    • 2
  • J. Schiefer
    • 2
  • I. Adamchic
    • 1
  • K. Lohfink
    • 1
  • M. Kandulski
    • 2
  • A. Heller
    • 2
  • P. R. Mertens
    • 2
  1. 1.Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöROtto-von-Guericke University MagdeburgMagdeburgGermany
  2. 2.Department of Nephrology and Hypertension, Diabetes and EndocrinologyUniversitätsklinikum Magdeburg AöRMagdeburgGermany
  3. 3.Deutsche Akademie für MikrotherapieMagdeburgGermany

Personalised recommendations