406
Letters to the Editor
References [1] Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation — developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385–413. [2] Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17. [3] Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92. [4] Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(11):39–51.
[5] Eikelboom JW, Connolly SJ, Hart RG, et al. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol 2013;62:900–8. [6] Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91. [7] Hori M, Matsumoto M, Tanahashi N, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study. Circ J 2012;76:2104–11. [8] Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093–104. [9] Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151:297–305. [10] Hong KS, Ali LK, Selco SL, Fonarow GC, Saver JL. Weighting components of composite end points in clinical trials: an approach using disability-adjusted life-years. Stroke 2011;42:1722–9.
http://dx.doi.org/10.1016/j.ijcard.2014.04.051 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Vascular response after percutaneous sympathectomy: Not all devices are equal☆ Francesco Versaci a,b,⁎,1, Antonio Trivisonno b,1, Carlo Olivieri b,1, Fiorella Caranci a,1, Luca Brunese c,1, Francesco Prati d,1 a b c d
Department of Cardiovascular Disease, Ospedale “Antonio Cardarelli”, Campobasso, Italy Department of Cardiovascular Disease, Ospedale “Ferdinando Veneziale”, Isernia, Italy Department of Medicine and Health Sciences, Università del Molise, Campobasso, Italy Department of Cardiovascular Disease, Ospedale “San Giovanni-Addolorata”, Rome, Italy
a r t i c l e
i n f o
Article history: Received 17 March 2014 Accepted 2 April 2014 Available online 15 April 2014 Keywords: Hypertension Renal denervation Peripheral vascular disease Renal artery Sympathectomy
Renal denervation (RDN) is an emerging treatment strategy in patients with resistant hypertension. It is generally a safe procedure with a low complication rate and without major side effects (1). However, recent reports demonstrated local tissue damage induced by radiofrequency (RF) energy delivery or asymptomatic artery dissection related to the procedure (2,3). Tissue injury might cause inflammation and fibrosis and could result in vessel stenosis at long-term follow-up (4). Currently there are multiple RDN systems with different features and treatment modalities (5). Data regarding the vascular injury induced by these new devices are lacking. We recently evaluated the vascular response after RDN using the Vessix™ Renal Denervation System (Boston Scientific Corporation, Natick, MA, USA). We report our preliminary data from a prospective observational study conducted between July and December 2013 in patients with resistant hypertension treated with RDN. All patients were on daily Aspirin 100 mg (started at least 2 weeks before the procedure). Heparin was administrated to achieve an ☆ Contributors' statement: There is no funding source and no conflict of interest. ⁎ Corresponding author at: Department of Cardiovascular Disease, Ospedale “Antonio Cardarelli”, 86100 Contrada Tappino, Campobasso, Italy. Tel./fax: +39 0874313427. E-mail address: [email protected] (F. Versaci). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
activated clotting time (ACT) of N250 s and intraprocedural diffuse visceral abdominal pain was managed with intravenous anxiolytics and narcotics. All procedures were performed by using a percutaneous femoral approach. An 8 French dedicated catheter to allow for passage of the renal denervation system was utilized. Selective angiograms and optical coherence tomography (OCT) (DragonFly catheter, St Jude Medical, LightLab Imaging) were performed on both renal arteries using a standard 6 French guiding catheter with telescopic technique. The balloon size was selected according to OCT or angiographic measurement. The balloon was slowly inflated into the lumen to 3 atm using a standard inflation device. Contrast medium was injected to verify the occlusion of the artery and to demonstrate the adequate apposition of the balloon against the vessel wall. Once balloon inflation was completed and the device was activated, the generator raised the electrode temperature to 68 °C, causing nerve ablation within 30 s. The bipolar electrodes ensured that the total amount of energy delivered to the artery was approximately 1 W. OCT imaging was performed before and after the ablation procedure. In each renal artery, at least one pullback was routinely obtained pre-RDN and post-RDN. Iomeron 300 mg/mL (Bracco Imaging Italia srl) contrast medium was used to flush renal arteries at a flow rate of 8.0 mL/s. Only good quality pullbacks were analyzed by an independent Core Lab (Rome Heart Research, Italy). All patients received a follow-up visit and blood pressure (BP) Holter monitoring in the hypertension Center of our hospital at 1, 3, and 6 months and 1 year, then every 6 months or more according to clinical status. Eight patients were enrolled, six males and two females. The average age was 56.8 ± 11.2 years. All patients had drug-resistant hypertension. BP at enrollment was PAS: 160 ± 9.4 mm Hg, and PAD 87 ± 6.5 mm Hg. The average number of antihypertensive drugs was 5.2 ± 1. The median procedure time was 40 ± 16 min. In total, 16 renal arteries were evaluated. Post-procedural renal angiograms did not demonstrate a significant decrease in renal artery diameter and irregularities at spots where RF energy was delivered. OCT imaging performed after renal denervation did not show local notches or intimal tears with overlying intraluminal thrombosis in the renal arteries where RF energy was delivered or
Letters to the Editor
407
Fig. 1. Right renal artery (A–D) and left renal artery (E–H). Baseline angiography (A and E) and OCT imaging (B and F) before renal denervation. Post-procedural angiography (C and G) does not demonstrate a significant decrease in renal artery diameter and irregularities at spots where RF energy was delivered. Post-procedural OCT (D and H) does not show local notches or intimal tears with overlying intraluminal thrombosis and intima–media thickening in the renal arteries.
artery dissection related to the procedure (Fig. 1). In one patient with renal arteries N7 mm OCT acquisition images were not adequate to be analyzed. We assessed office-based BP reduction at 1 week and at 1 and 3 months. A significant reduction in both systolic BP and diastolic BP was observed since one week after the procedure. At all followup visits after the procedure, both systolic and diastolic BP values were lower than baseline BP. Mean reductions in office BP were − 23/10 mm Hg and − 25/10 mm Hg at 1 and 3 months, respectively (p b 0.05). In 3 cases after the procedure there was an immediate significant BP reduction requiring a significant reduction of anti-hypertensive therapy. All patients were followed in the office and no hospitalizations occurred. Catheter-based RDN ablation using RF energy is a novel treatment for drug-resistant hypertension. Recent studies with OCT performed immediately after RDN demonstrated local tissue damage not apparent with angiography, i.e., local and diffuse vasospasm, edema formation, local notches, evident intimal disruptions and accompanying intraluminal thrombi. These findings were demonstrated with Symplicity Flex (Medtronic) renal denervation system and with EnligHTN (St. Jude Medical, Inc., St. Paul, MN, USA) (2). Dissections not requiring additional treatment were described in three renal arteries treated with OneShot RDN (Covidien, Mansfield, MA, USA) (3). Abnormal vascular injury after RDN is a critical issue because it could be a possible trigger of arterial disease resulting in vessel stenosis during follow-up (4). Our study suggests that the use of the Vessix™ Renal Denervation System is able to reduce BP levels since the first week after the RDN procedure in a small patient population. Moreover, to date this is the first report on OCT imaging after Vessix™ Renal Denervation System use and provides important insights on the acute effects of this new device on renal arteries. Probably the different mechanhttp://dx.doi.org/10.1016/j.ijcard.2014.04.049 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
ism of renal denervation with low power RF delivery in a shorter time by a low pressure noncompliant-balloon embedded with a helical array of bipolar electrodes does not cause the diffuse renal artery constriction and local tissue injury at the ablation site observed with other renal denervation systems. Renal artery OCT is feasible in most patients before and after RDN and is useful for detecting acute vascular injury after the procedure. OCT after RDN allows us to better understand the differences in terms of local vascular damage between the different ablation systems. In this context, among the second-generation RDN devices, the VessixTM Renal Denervation System minimizing vascular tissue injury is very promising. Larger studies with longterm reliable imaging follow-up are needed to confirm these findings that could represent an important insight for the safety of this new RDN system. Only if the related complication rate is very low, RDN will represent an additional strategy to conventional antihypertensive therapy in patients with resistant hypertension. References [1] 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 randomized controlled trial. Lancet 2010;376:1903–9. [2] Templin C, Jaguszewski M, Ghadri JR, et al. Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and postprocedural comparison with the Simplicity® catheter system and the EnligHTN ™ multi-electrode renal denervation catheter. Eur Heart J 2013;34(28):2141–8. [3] Stabile E, Ambrosini V, Squarcia R, et al. Percutaneous sympathectomy of the renal arteries: the OneShotTM Renal Denervation System is not associated with significant vessel wall injury. EuroIntervention 2013;9:694–9. [4] Versaci F, Trivisonno A, Olivieri C, Caranci F, Brunese L, Prati F. Late renal artery stenosis after renal denervation: is it the tip of the iceberg? Int J Cardiol 2014;172(3):e507–8. [5] Daemen J. Current technologies: an introduction. EuroIntervention 2013;9:R75–82.
Letters to the Editor
References [1] Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation — developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385–413. [2] Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17. [3] Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92. [4] Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(11):39–51.
[5] Eikelboom JW, Connolly SJ, Hart RG, et al. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol 2013;62:900–8. [6] Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91. [7] Hori M, Matsumoto M, Tanahashi N, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study. Circ J 2012;76:2104–11. [8] Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093–104. [9] Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151:297–305. [10] Hong KS, Ali LK, Selco SL, Fonarow GC, Saver JL. Weighting components of composite end points in clinical trials: an approach using disability-adjusted life-years. Stroke 2011;42:1722–9.
http://dx.doi.org/10.1016/j.ijcard.2014.04.051 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Vascular response after percutaneous sympathectomy: Not all devices are equal☆ Francesco Versaci a,b,⁎,1, Antonio Trivisonno b,1, Carlo Olivieri b,1, Fiorella Caranci a,1, Luca Brunese c,1, Francesco Prati d,1 a b c d
Department of Cardiovascular Disease, Ospedale “Antonio Cardarelli”, Campobasso, Italy Department of Cardiovascular Disease, Ospedale “Ferdinando Veneziale”, Isernia, Italy Department of Medicine and Health Sciences, Università del Molise, Campobasso, Italy Department of Cardiovascular Disease, Ospedale “San Giovanni-Addolorata”, Rome, Italy
a r t i c l e
i n f o
Article history: Received 17 March 2014 Accepted 2 April 2014 Available online 15 April 2014 Keywords: Hypertension Renal denervation Peripheral vascular disease Renal artery Sympathectomy
Renal denervation (RDN) is an emerging treatment strategy in patients with resistant hypertension. It is generally a safe procedure with a low complication rate and without major side effects (1). However, recent reports demonstrated local tissue damage induced by radiofrequency (RF) energy delivery or asymptomatic artery dissection related to the procedure (2,3). Tissue injury might cause inflammation and fibrosis and could result in vessel stenosis at long-term follow-up (4). Currently there are multiple RDN systems with different features and treatment modalities (5). Data regarding the vascular injury induced by these new devices are lacking. We recently evaluated the vascular response after RDN using the Vessix™ Renal Denervation System (Boston Scientific Corporation, Natick, MA, USA). We report our preliminary data from a prospective observational study conducted between July and December 2013 in patients with resistant hypertension treated with RDN. All patients were on daily Aspirin 100 mg (started at least 2 weeks before the procedure). Heparin was administrated to achieve an ☆ Contributors' statement: There is no funding source and no conflict of interest. ⁎ Corresponding author at: Department of Cardiovascular Disease, Ospedale “Antonio Cardarelli”, 86100 Contrada Tappino, Campobasso, Italy. Tel./fax: +39 0874313427. E-mail address: [email protected] (F. Versaci). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
activated clotting time (ACT) of N250 s and intraprocedural diffuse visceral abdominal pain was managed with intravenous anxiolytics and narcotics. All procedures were performed by using a percutaneous femoral approach. An 8 French dedicated catheter to allow for passage of the renal denervation system was utilized. Selective angiograms and optical coherence tomography (OCT) (DragonFly catheter, St Jude Medical, LightLab Imaging) were performed on both renal arteries using a standard 6 French guiding catheter with telescopic technique. The balloon size was selected according to OCT or angiographic measurement. The balloon was slowly inflated into the lumen to 3 atm using a standard inflation device. Contrast medium was injected to verify the occlusion of the artery and to demonstrate the adequate apposition of the balloon against the vessel wall. Once balloon inflation was completed and the device was activated, the generator raised the electrode temperature to 68 °C, causing nerve ablation within 30 s. The bipolar electrodes ensured that the total amount of energy delivered to the artery was approximately 1 W. OCT imaging was performed before and after the ablation procedure. In each renal artery, at least one pullback was routinely obtained pre-RDN and post-RDN. Iomeron 300 mg/mL (Bracco Imaging Italia srl) contrast medium was used to flush renal arteries at a flow rate of 8.0 mL/s. Only good quality pullbacks were analyzed by an independent Core Lab (Rome Heart Research, Italy). All patients received a follow-up visit and blood pressure (BP) Holter monitoring in the hypertension Center of our hospital at 1, 3, and 6 months and 1 year, then every 6 months or more according to clinical status. Eight patients were enrolled, six males and two females. The average age was 56.8 ± 11.2 years. All patients had drug-resistant hypertension. BP at enrollment was PAS: 160 ± 9.4 mm Hg, and PAD 87 ± 6.5 mm Hg. The average number of antihypertensive drugs was 5.2 ± 1. The median procedure time was 40 ± 16 min. In total, 16 renal arteries were evaluated. Post-procedural renal angiograms did not demonstrate a significant decrease in renal artery diameter and irregularities at spots where RF energy was delivered. OCT imaging performed after renal denervation did not show local notches or intimal tears with overlying intraluminal thrombosis in the renal arteries where RF energy was delivered or
Letters to the Editor
407
Fig. 1. Right renal artery (A–D) and left renal artery (E–H). Baseline angiography (A and E) and OCT imaging (B and F) before renal denervation. Post-procedural angiography (C and G) does not demonstrate a significant decrease in renal artery diameter and irregularities at spots where RF energy was delivered. Post-procedural OCT (D and H) does not show local notches or intimal tears with overlying intraluminal thrombosis and intima–media thickening in the renal arteries.
artery dissection related to the procedure (Fig. 1). In one patient with renal arteries N7 mm OCT acquisition images were not adequate to be analyzed. We assessed office-based BP reduction at 1 week and at 1 and 3 months. A significant reduction in both systolic BP and diastolic BP was observed since one week after the procedure. At all followup visits after the procedure, both systolic and diastolic BP values were lower than baseline BP. Mean reductions in office BP were − 23/10 mm Hg and − 25/10 mm Hg at 1 and 3 months, respectively (p b 0.05). In 3 cases after the procedure there was an immediate significant BP reduction requiring a significant reduction of anti-hypertensive therapy. All patients were followed in the office and no hospitalizations occurred. Catheter-based RDN ablation using RF energy is a novel treatment for drug-resistant hypertension. Recent studies with OCT performed immediately after RDN demonstrated local tissue damage not apparent with angiography, i.e., local and diffuse vasospasm, edema formation, local notches, evident intimal disruptions and accompanying intraluminal thrombi. These findings were demonstrated with Symplicity Flex (Medtronic) renal denervation system and with EnligHTN (St. Jude Medical, Inc., St. Paul, MN, USA) (2). Dissections not requiring additional treatment were described in three renal arteries treated with OneShot RDN (Covidien, Mansfield, MA, USA) (3). Abnormal vascular injury after RDN is a critical issue because it could be a possible trigger of arterial disease resulting in vessel stenosis during follow-up (4). Our study suggests that the use of the Vessix™ Renal Denervation System is able to reduce BP levels since the first week after the RDN procedure in a small patient population. Moreover, to date this is the first report on OCT imaging after Vessix™ Renal Denervation System use and provides important insights on the acute effects of this new device on renal arteries. Probably the different mechanhttp://dx.doi.org/10.1016/j.ijcard.2014.04.049 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
ism of renal denervation with low power RF delivery in a shorter time by a low pressure noncompliant-balloon embedded with a helical array of bipolar electrodes does not cause the diffuse renal artery constriction and local tissue injury at the ablation site observed with other renal denervation systems. Renal artery OCT is feasible in most patients before and after RDN and is useful for detecting acute vascular injury after the procedure. OCT after RDN allows us to better understand the differences in terms of local vascular damage between the different ablation systems. In this context, among the second-generation RDN devices, the VessixTM Renal Denervation System minimizing vascular tissue injury is very promising. Larger studies with longterm reliable imaging follow-up are needed to confirm these findings that could represent an important insight for the safety of this new RDN system. Only if the related complication rate is very low, RDN will represent an additional strategy to conventional antihypertensive therapy in patients with resistant hypertension. References [1] 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 randomized controlled trial. Lancet 2010;376:1903–9. [2] Templin C, Jaguszewski M, Ghadri JR, et al. Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and postprocedural comparison with the Simplicity® catheter system and the EnligHTN ™ multi-electrode renal denervation catheter. Eur Heart J 2013;34(28):2141–8. [3] Stabile E, Ambrosini V, Squarcia R, et al. Percutaneous sympathectomy of the renal arteries: the OneShotTM Renal Denervation System is not associated with significant vessel wall injury. EuroIntervention 2013;9:694–9. [4] Versaci F, Trivisonno A, Olivieri C, Caranci F, Brunese L, Prati F. Late renal artery stenosis after renal denervation: is it the tip of the iceberg? Int J Cardiol 2014;172(3):e507–8. [5] Daemen J. Current technologies: an introduction. EuroIntervention 2013;9:R75–82.
