LETTER
TO
THE
EDITOR
Renal Sympathetic Denervation in a Previously Stented Renal Artery To the Editor: Despite the development of numerous antihypertensive medications and the use of multidrug therapy, about 5% to 20% of all hypertensive patients are resistant to medical therapy.1 Sympathetic overdrive is responsible for the development and maintenance of resistant hypertension (RH). In the kidney, efferent sympathetic activity promotes Na+ re-absorption and renin release, while afferent nerves stimulate central sympathetic outflow and produce vasoconstriction. The physiological basis of renal sympathetic denervation (RDN) is the suppression of the hyperadrenergic state by the interruption of the renal sympathetic nerve fibers. Two trials2,3—Symplicity HTN-1 and Symplicity HTN-2—have demonstrated the efficacy and the safety of RDN in patients with RH. In these trials, patients with renal artery stenosis or stent were excluded; therefore, there are few data about RDN in these patients. Moreover, a meta-analysis did not find an improvement in blood pressure (BP) in patients with renal artery stenosis treated with renal artery stenting.4 Therefore, a double mechanism maintains hypertension: renovascular and sympathetic tone. In the following, we report the case of a patient with RH treated by RDN after renal artery stenting. A 54-year-old man was admitted to our unit for resistant hypertension (office BP 220/120 mm Hg) despite treatment with 5 antihypertensive agents. During secondary hypertension evaluation, angiography demonstrated a high-grade right renal artery stenosis, which was treated with angioplasty and stenting. Office BP values after angioplasty were 140/90 mm Hg during the first month, but BP returned close to baseline after 3 months. Remarkably, there was no restenosis on results of Doppler imaging. The patient subsequently underwent radiofrequency ablation of both renal arteries using Medtronic’s Symplicity Catheter System (Medtronic, Inc, Minneapolis, MN). Because of the presence of a right renal artery stent, ablation on this side was performed only at the distal segment of the renal artery, distal to the stent. The distance between the stent and the first point of renal ablation was 25 mm. The procedure was completed without complications. After 1 month, office BP decreased from 175/120 mm Hg to 140/90 mm Hg and mean 24-hour ambulatory BP from 164/98 mm Hg to 130/81 mm Hg. Medical therapy remained unchanged. No renal artery stenoses were shown on Doppler ultrasound examination at 1 month (Figure 1 and Figure 2). Johansson’s and Miyajima’s clinical studies5–7 underlined the relevance not only of the renin-angiotensin system but also of adrenergic overactivity in renovascular hypertension. Johansson and Elam5 compared arterial plasma renin activity (PRA), angiotensin II (ATII), norepinephrine (NE) spillover, and muscle-
doi: 10.1111/jch.12251
238
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
FIGURE 1. Catheter for renal denervation inside the renal artery beyond the stent.
FIGURE 2. 24h blood pressure values before and one month after renal denervation.
sympathetic-nerve activity (MSNA) between hypertensive patients with renal artery stenosis and healthy patients. Not only were PRA and ATII higher in the first group but NE spillover and MSNA were also increased. Likewise, Miyajima and colleagues7 observed that in some patients who underwent renal artery balloon angioplasty, sympathetic tone remained higher than in normotensive patients. Therefore, in renovascular hypertension, elevated BP is caused by renin-angiotensin system and sympathetic overactivity. This could explain why in some patients, BP is uncontrolled after renal artery balloon angioplasty.8 To our knowledge, this is the second case of RDN in a formerly stented renal artery. As in Ziegler’s case,9 also in our patient, BP values decreased significantly after RDN, whereas this happened transiently after renal artery angioplasty and
Letter to the Editor
stenting. RDN after renal artery stenting is not risk-free, the main concern being heating of the stent and the resulting coagulative necrosis around it.10,11 Therefore, it is necessary to leave a safety distance between the stent and the first spot where radiofrequency ablation is performed, which is possible only if the renal artery is long enough. In our experience, the procedure is feasible and effective in patients with resistant hypertension and treated renal artery stenosis, provided that the anatomy of the renal artery is compatible with the intervention. Funding: This work was not supported by any financial funding. Disclosures: We declare no conflict of interest.
Elena Berra, MD; Franco Rabbia, MD; Denis Rossato, MD; Michele Covella, MD; Silvia Totaro, MD; Fulcheri Chiara, MD; Silvia Di Monaco, MS; Franco Veglio, MD Department of Medical Sciences, University of Turin, Turin, Italy References 1. Calhoun DA, Jones D, Textor S, et al. American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American
2.
3.
4. 5. 6. 7. 8. 9. 10. 11.
Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–e526. 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– 1281. Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatmentresistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–1909. Shetty R, Biondi-Zoccai GG, Abbate A, et al. Percutaneous renal artery intervention versus medical therapy in patients with renal artery stenosis: a meta-analysis. EuroIntervention. 2011;7:844–851. Johansson M, Elam M. Increased sympathetic nerve activity in renovascular hypertension. Circulation. 1999; 99 :2537–2542. Johansson M, Friberg P. Role of the sympathetic nervous system in human renovascular hypertension. Curr Hypertens Rep. 2000; 2:319– 326. Miyajima E, Yamada Y, Yoshida Y, et al. Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism. Hypertension. 1991;17:1057–1062. Ramsay LE, Waller PC. Blood pressure response to percutaneous transluminal angioplasty for renovascular hypertension: an overview of published series. BMJ. 1990; 300:569–572. Ziegler AK, Franke J, Bertoq SC. Renal denervation in a patient with prior renal artery stenting. Catheter Cardiovasc Interv. 2013; 81:342– 345. Patel H, di Mario C. Microwaving metal! Can you get away with it? Renal denervation after stenting. Catheter Cardiovasc Interv. 2013;81:346–347. Goldberg SN, Ryan TP, Hanh PF, et al. Transluminal radiofrequency tissue ablation with use of metallic stent. J Vasc Interv Radiol. 1997;8:835–843.
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
239
TO
THE
EDITOR
Renal Sympathetic Denervation in a Previously Stented Renal Artery To the Editor: Despite the development of numerous antihypertensive medications and the use of multidrug therapy, about 5% to 20% of all hypertensive patients are resistant to medical therapy.1 Sympathetic overdrive is responsible for the development and maintenance of resistant hypertension (RH). In the kidney, efferent sympathetic activity promotes Na+ re-absorption and renin release, while afferent nerves stimulate central sympathetic outflow and produce vasoconstriction. The physiological basis of renal sympathetic denervation (RDN) is the suppression of the hyperadrenergic state by the interruption of the renal sympathetic nerve fibers. Two trials2,3—Symplicity HTN-1 and Symplicity HTN-2—have demonstrated the efficacy and the safety of RDN in patients with RH. In these trials, patients with renal artery stenosis or stent were excluded; therefore, there are few data about RDN in these patients. Moreover, a meta-analysis did not find an improvement in blood pressure (BP) in patients with renal artery stenosis treated with renal artery stenting.4 Therefore, a double mechanism maintains hypertension: renovascular and sympathetic tone. In the following, we report the case of a patient with RH treated by RDN after renal artery stenting. A 54-year-old man was admitted to our unit for resistant hypertension (office BP 220/120 mm Hg) despite treatment with 5 antihypertensive agents. During secondary hypertension evaluation, angiography demonstrated a high-grade right renal artery stenosis, which was treated with angioplasty and stenting. Office BP values after angioplasty were 140/90 mm Hg during the first month, but BP returned close to baseline after 3 months. Remarkably, there was no restenosis on results of Doppler imaging. The patient subsequently underwent radiofrequency ablation of both renal arteries using Medtronic’s Symplicity Catheter System (Medtronic, Inc, Minneapolis, MN). Because of the presence of a right renal artery stent, ablation on this side was performed only at the distal segment of the renal artery, distal to the stent. The distance between the stent and the first point of renal ablation was 25 mm. The procedure was completed without complications. After 1 month, office BP decreased from 175/120 mm Hg to 140/90 mm Hg and mean 24-hour ambulatory BP from 164/98 mm Hg to 130/81 mm Hg. Medical therapy remained unchanged. No renal artery stenoses were shown on Doppler ultrasound examination at 1 month (Figure 1 and Figure 2). Johansson’s and Miyajima’s clinical studies5–7 underlined the relevance not only of the renin-angiotensin system but also of adrenergic overactivity in renovascular hypertension. Johansson and Elam5 compared arterial plasma renin activity (PRA), angiotensin II (ATII), norepinephrine (NE) spillover, and muscle-
doi: 10.1111/jch.12251
238
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
FIGURE 1. Catheter for renal denervation inside the renal artery beyond the stent.
FIGURE 2. 24h blood pressure values before and one month after renal denervation.
sympathetic-nerve activity (MSNA) between hypertensive patients with renal artery stenosis and healthy patients. Not only were PRA and ATII higher in the first group but NE spillover and MSNA were also increased. Likewise, Miyajima and colleagues7 observed that in some patients who underwent renal artery balloon angioplasty, sympathetic tone remained higher than in normotensive patients. Therefore, in renovascular hypertension, elevated BP is caused by renin-angiotensin system and sympathetic overactivity. This could explain why in some patients, BP is uncontrolled after renal artery balloon angioplasty.8 To our knowledge, this is the second case of RDN in a formerly stented renal artery. As in Ziegler’s case,9 also in our patient, BP values decreased significantly after RDN, whereas this happened transiently after renal artery angioplasty and
Letter to the Editor
stenting. RDN after renal artery stenting is not risk-free, the main concern being heating of the stent and the resulting coagulative necrosis around it.10,11 Therefore, it is necessary to leave a safety distance between the stent and the first spot where radiofrequency ablation is performed, which is possible only if the renal artery is long enough. In our experience, the procedure is feasible and effective in patients with resistant hypertension and treated renal artery stenosis, provided that the anatomy of the renal artery is compatible with the intervention. Funding: This work was not supported by any financial funding. Disclosures: We declare no conflict of interest.
Elena Berra, MD; Franco Rabbia, MD; Denis Rossato, MD; Michele Covella, MD; Silvia Totaro, MD; Fulcheri Chiara, MD; Silvia Di Monaco, MS; Franco Veglio, MD Department of Medical Sciences, University of Turin, Turin, Italy References 1. Calhoun DA, Jones D, Textor S, et al. American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American
2.
3.
4. 5. 6. 7. 8. 9. 10. 11.
Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–e526. 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– 1281. Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatmentresistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–1909. Shetty R, Biondi-Zoccai GG, Abbate A, et al. Percutaneous renal artery intervention versus medical therapy in patients with renal artery stenosis: a meta-analysis. EuroIntervention. 2011;7:844–851. Johansson M, Elam M. Increased sympathetic nerve activity in renovascular hypertension. Circulation. 1999; 99 :2537–2542. Johansson M, Friberg P. Role of the sympathetic nervous system in human renovascular hypertension. Curr Hypertens Rep. 2000; 2:319– 326. Miyajima E, Yamada Y, Yoshida Y, et al. Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism. Hypertension. 1991;17:1057–1062. Ramsay LE, Waller PC. Blood pressure response to percutaneous transluminal angioplasty for renovascular hypertension: an overview of published series. BMJ. 1990; 300:569–572. Ziegler AK, Franke J, Bertoq SC. Renal denervation in a patient with prior renal artery stenting. Catheter Cardiovasc Interv. 2013; 81:342– 345. Patel H, di Mario C. Microwaving metal! Can you get away with it? Renal denervation after stenting. Catheter Cardiovasc Interv. 2013;81:346–347. Goldberg SN, Ryan TP, Hanh PF, et al. Transluminal radiofrequency tissue ablation with use of metallic stent. J Vasc Interv Radiol. 1997;8:835–843.
The Journal of Clinical Hypertension
Vol 16 | No 3 | March 2014
239
