Renal sympathetic denervation in patients with vasospastic angina

  • Lida Feyz
  • Maureen Henneman
  • Fred Verzijlbergen
  • Isabella Kardys
  • Nicolas M. Van Mieghem
  • Joost DaemenEmail author
Open Access
Original Article



Sympathetic overactivity has been linked to vasospastic angina (VSA), although the exact pathophysiology of VSA is poorly understood. The purpose of this study is to assess if renal sympathetic denervation (RDN) reduces cardiac sympathetic nerve activity with a subsequent beneficial effect on angina relief in patients with refractory VSA.

Methods and results

Cardiac sympathetic nerve activity was assessed prior to procedure and at 6 months post-procedure using iodine-123 labeled meta-iodobenzylguanidine (123I-MIBG) imaging. The Seattle Angina questionnaire (SAQ) was used to assess the degree to which the disease impacts quality of life. No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76), and late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). Additionally, no change was seen in WR (P = 0.22). SAQ results revealed significant improvements in perceived physical limitation, angina frequency, and quality of life at 6 months (P < 0.05 for all).


RDN resulted in improvements in angina class and quality of life at 6 months in patients with refractory VSA. RDN, however, did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG. The latter observation should be considered with caution given the small sample size of this study. Larger studies are needed to assess this further.


Renal sympathetic denervation vasospastic angina MIBG meta-iodobenzylguanidine quality of life 


24h ABPM

24h ambulatory blood pressure measurement


Computed tomography


Heart-to-mediastinum ratio


Iodine-123 labeled meta-iodobenzylguanidine


Magnetic resonance imaging




Renal sympathetic denervation


Sympathetic nervous system


Vasospastic angina


Washout rates


Vasospastic angina (VSA) is a clinical syndrome that was first described by Prinzmetal et al. in 1959.1 Although the syndrome has been characterized by episodes of coronary artery vasospasm, the exact pathophysiology of spasms is poorly understood. While studies from the early ‘80s and ‘90s already demonstrated that both the sympathetic and parasympathetic nervous system are responsible for coronary vasomotion, more recent work demonstrated significant hyperactivity of the sympathetic nervous system (SNS) in patients with VSA as compared to healthy controls.2, 3, 4 The majority of VSA patients present with refractory angina; however, the disease appears not benign. Syncope and ventricular arrhythmias are the first clinical presentation in up to 40% of the cases and the risk for sudden death may be increased by up to 50%.5, 6, 7, 8 Current treatment options are mainly pharmacological and include the use of long-acting nitrates and calcium channel blockers, which showed to provide symptom improvement in 30 to 80% of the cases, respectively.9 Looking for more effective treatments, several small studies showed that surgical (cardiac) sympathetic denervation resulted in a significantly lower number of angina episodes and ST-segment deviations on 24h holter monitoring.10,11 In the present study, we hypothesized that renal sympathetic denervation (RDN), a percutaneous treatment that proved to significantly lower blood pressure and systemic sympathetic nerve activity in hypertensive patients, might provide additional angina relief in patients with VSA. In order to quantify the potential effect of RDN on cardiac sympathetic nerve activity, iodine-123-labeled meta-iodobenzylguanidine (123I-MIBG) scintigraphy was used.12,13


Study Population and Endpoints

Between April 2013 and August 2016, a total of 10 consecutive patients with refractory VSA underwent RDN. Patients were eligible in case of refractory angina. Significant residual coronary artery stenosis was ruled out and patency of previously implanted stents was confirmed in all cases by recent coronary angiography. Coronary physiologic assessment using fractional flow reserve was used in case of intermediate lesions.

VSA was confirmed in case of spontaneous or methylergonovine-induced spasms with ST-segment changes and symptoms of chest pain in 6 out of 10 patients. In 4 patients, the diagnosis was based on the presence of recurrent episodes of non-exercise-induced angina, which resolved after sublingual nitrates and in the absence of significant atherosclerotic coronary artery disease.

Patients were screened for RDN and followed according to routine clinical practice. Work-up included 24h ambulatory blood pressure measurement (24h ABPM), laboratory analysis, echocardiography, and CT (N = 2), MRI (N = 7) or renal duplex (N = 1) to confirm renal artery eligibility.

Follow-up in the outpatient clinic at 1, 3, and 6 months post-RDN included 24h ABPM (at 3 and 6 months) and echocardiography (at 6 months). Renal function was assessed at baseline and at follow-up. Renal artery imaging was performed at 6 months to confirm renal artery patency.

For the purpose of this, study patients were not subjects to acts, neither was any mode of behavior imposed, otherwise than as part of their regular treatment. Therefore, according to Dutch law, written informed consent for study enrolment was obtained. This study was conducted according to the privacy policy of the Erasmus Medical Center and the Erasmus Medical Center regulations for the appropriate use of data in patient-orientated research, which are based on international regulations, including the Declaration of Helsinki. All patients consented to the use of their data for scientific research.

The primary efficacy endpoint was the change in cardiac sympathetic nerve activity as measured using 123I-MIBG imaging at 6 months post-RDN, as compared to pre-RDN (baseline). The primary safety endpoint was defined as the occurrence of cardiovascular death, stroke, major access site bleeding, and acute kidney injury or renal artery stenosis at 6-month follow-up.

Secondary endpoints included the changes in Canadian Cardiovascular Society grading (CCS class), blood pressure (24h ABPM and office blood pressure), and heart rate. The Seattle Angina Questionnaire (SAQ) was used to assess the quality of life and signs and symptoms of angina.

123I-MIBG Scintigraphy Data Acquisition and Analysis

123I-MIBG is a physiologic analog of norepinephrine and acts selectively on sympathetic nerve endings. By using cardiac neurotransmission imaging, global information about neuronal function can be expressed in early, but more specifically in late HMR (reflecting the storage regional distribution and release of 123I-MIBG), with washout rate (WR) reflecting the neuronal integrity or sympathetic tone.14 In order to block thyroid uptake of free radioactive iodide, 200 mg potassium iodide (10% solution) was administered. After 30 minutes, 185 MBq 123I-MIBG was administered intravenously. Early and late (i.e., 15 minutes and 4 hours after tracer injection, respectively) anterior planar scintigraphic images were acquired for 10 minutes with a zoom factor of 1.0 and stored in a 256 × 256 matrix. Patients were imaged in a supine position with a dual head gamma camera (Symbia T, Siemens, Erlangen, Germany), using a medium energy collimator. An energy window of ± 10% was symmetrically centered around the 159-KeV 123I photo peak. Offline processing software (Hermes Medical Solutions Workstation) was used to draw a round region of interest (ROI) with fixed diameter over the upper mediastinum, below the thyroid gland (Figure 1). Additionally, a manual ROI over the heart was drawn, carefully excluding adjacent activity in the liver and lung. The left ventricular cavity was included in the myocardial ROI. The MIBG images were scored by a dedicated nuclear medicine specialist blinded to the timing of the scan. The HMR was computed by dividing the average number of counts within the cardiac ROI by the average number of counts within the mediastinal ROI. Calculation of WR was performed using the following formula (no correction for background): WR= (HMRearly − HMRlate)/(HMRearly) × 100%.15
Figure 1

Example of MIBG image scoring with early and late HMR. Early HMR at baseline (A1) was 3.11 and changed to 3.35 at 6 months (A2), while late HMR at baseline was 3.23 (B1) and changed to 3.51 at 6-month (B2) follow-up. (A) 15 min after tracer injection, (B) 4 h after tracer injection

RDN Procedure

Pre-procedurally, 100IU heparin/kg was administered to achieve an active clotting time > 250 seconds. All procedures were performed under conscious sedation. After administration of local anesthesia, common femoral artery access was achieved by an ultrasound-guided puncture and a 7-Fr sheath was then introduced. A 7-Fr guiding catheter was used to accommodate the ParadiseTM RDN catheter (ReCor Medical, Palo Alto, CA).16 After smoothly engaging the renal arteries by using a no-touch technique with the help of a standard high-torque BHW coronary guidewire, selective renal artery angiograms were made. The ParadiseTM system ablation catheter was then advanced over the BHW wire. The ParadiseTM catheter has a distal balloon which is pressurized by the Paradise system to a range of 1.5 to 2.0 ATM using sterile circulating water. The ultrasound transducer is located within the balloon (balloon diameters 5 to 8 mm). A total of 2 to 3 ultrasound emissions of 6 to 10 seconds each were delivered per artery.

Statistical Analysis

Continuous variables were expressed as mean ± standard deviation (SD). Continuous variables were compared using Student’s t test. Categorical variables were expressed as percentages and were compared using the χ2 test or Fisher’s Exact test when appropriate. Early and late HMR and WR were compared using the Wilcoxon signed-rank test. All statistical tests are 2-tailed. A P value < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS statistical analysis (version 22.0).


Study Population

Mean age of the patients was 57 ± 11 years, 90% were male, and 90% were in CCS class III or IV. None of the patients had diabetes, and hypertension was present in 80% of the cases.

All patients were using anti-anginal therapy using long-acting nitrates (10/10) and calcium channel blockers (8/10). Most patients had a history of prior coronary revascularization (Table 1).
Table 1

Baseline characteristics

Total study population N=10

Age, years

57 ± 11

Male n, (%)

9 (90)

BMI, kg/m2

26.6 ± 5.0

eGFR, mL/min

76 ± 17

Cardiovascular risk factors (%)


0 (0)


8 (80)


9 (90)

 Smoker, current

3 (30)

 Family history of premature CVD

7 (70)

Cardiovascular history (%)

 Prior MI

7 (70)

 Prior PCI

8 (80)

 24h ABPM, mmHg

121 ± 16/72 ± 8

 Office BP, mmHg

143 ± 19/80 ± 10

 Heart rate, bpm

62 ± 8

Angina-grading scale



1 (10)


8 (80)


1 (10)

Echocardiographic parameters

 LVEF, %

59 ± 9.6

 LVEDD, mm

50 ± 6.1

 LVESD, mm

34 ± 4.9

Pharmacological therapy, n (%)


10 (100)

 Calcium channel blockersa

8 (80)a

 Selective beta-blockers

5 (50)


8 (80)


10 (100)


4 (40)


10 (100)

Variables are presented in mean ± SD or %

ABPM, ambulatory blood pressure measurement; BP, blood pressure; BMI, body mass index; CCS, Canadian cardiovascular society grading of angina pectoris; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; PCI, percutaneous coronary intervention

aN=2 were intolerant for calcium channel blockers

Primary Efficacy Endpoint

123I-MIBG change

No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76) and in late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). No significant change was observed in WR (pre-RDN: 15.0 [10.5 to 18.5] vs 6 months post-RDN: 13.0 [6.0 to 22.0]; P = 0.22) (Table 2).
Table 2

Cardiac sympathetic nerve activity measured by 123I-MIBG pre- and 6 months post-procedure, expressed in median [IQR]



6 months


Early HMR

2.74 [2.10–3.21]

2.57 [2.20–3.00]


Late HMR

2.56 [2.18–3.20]

2.36 [2.13–3.22]



15.0 [10.5–18.5]

13.0 [6.0–22.0]


Variables are presented in mean ± SD

HMR, heart/mediastinum ratio; WR, washout rate

Primary Safety Endpoints

There were no peri-procedural complications. No adverse events including death, stroke, or renal artery stenosis occurred during 6-month follow-up. Renal function remained unchanged, and estimated glomerular filtration rate (eGFR) was 76 ± 17 mL/min pre-RDN vs 75 ± 18 mL/min at 6-month follow-up (P = 0.68).

Secondary Endpoints

Outcome on angina and quality of life

CCS class improved significantly from 3.00 ± 0.47 (pre-RDN) to 1.80 ± 0.92 at 6-month follow-up, P = 0.005.

The SAQ results showed significant improvements in 3/5 subscales at 3- and 6-month follow-up; patients were less limited in daily activities due to angina; angina frequency decreased significantly and quality of life improved as compared to pre-RDN. Angina stability and treatment satisfaction remained unchanged at 3- and 6-month follow-up (Figure 2).
Figure 2

Seattle Angina Questionnaire (SAQ) SAQ scale (each scale is a score of 0 to 100, wherein higher scores indicate better function or less angina/limitation and better quality of life)

Blood pressure change

A numerical decrease in both office- and ambulatory BP at 6 months was found as compared to pre-RDN. Office BP changed from 143 ± 19/80 ± 10 mmHg pre-RDN to 132 ± 12/77 ± 7 mmHg at 6-month follow-up and 24h ABPM decreased from 121 ± 16/72 ± 8mmHg to 112 ± 8/70 ± 7 mmHg (P = ns for all).

Change in medication

During the course of the study, long-acting nitrates and calcium channel blockers were decreased or stopped in 4 patients, while dosages were increased in 3 patients (Figure 3).
Figure 3

Change in early and late heart-to-mediastinum ratio (HMR), and washout rates (WR) at 6-month follow-up. Legend: 5 patients were off beta-blocker (red bullet) during the course of the study; 2 patients were on beta-blockers (same dose) at baseline and follow-up; 3 patients had beta-blockers at baseline and their dosage was halved (N = 2) and N = 1 was stopped at 6 months. In 5 patients, no washout rate (WR) could be calculated at baseline or 6 months


This present single-center pilot study demonstrated that RDN might significantly improve quality of life at 6 months post-procedure. However, no significant change was observed in cardiac sympathetic nerve activity as assessed by 123I-MIBG at 6 months post-procedure.

The autonomic nervous system is a key regulator of coronary vasomotion and an imbalance between the sympathetic and parasympathetic nervous system has been reported in patients with VSA.4,17,18 Provocation testing with parasympathetic agents such as acetylcholine or ergonovine can be performed in an attempt to confirm the diagnosis.19 In vitro, sympathetic agents like norepinephrine were used to test the severity of vasoconstriction or spasm.20

In the present study, we directly assessed cardiac sympathetic nerve activity by 123I-MIBG imaging, in line with previous work demonstrating the potential use of the technique in diagnosing VSA.21123I-MIBG is a physiologic analog of norepinephrine and acts selectively on sympathetic nerve endings. By using cardiac neurotransmission imaging, global information about neuronal function can be expressed in early, but more specifically in late HMR (reflecting the storage regional distribution and release of 123I-MIBG); additionally, the WR reflects the neuronal integrity or sympathetic tone.14123I-MIBG uptake is quantified by calculating an HMR after drawing regions of interest over the heart and mediastinum. Normal values for HMR and WR are 2.5 ± 0.3 or greater and 20 ± 10% or less, respectively.22 Little data are available on reference values in patients with VSA. Taki et al. reported higher WR in patients with VSA, probably due to increased sympathetic tone resulting in increased turnover of MIBG or impaired MIBG reuptake at the nerve endings.23,24 In addition, Arbab et al. showed a late HMR of 1.80 ± 0.60 in nine patients with VSA which was numerically lower as compared to healthy controls (2.00 ± 0.36).25 In the present study, pre-RDN HMR and WR were in line with previously published reference values for healthy control groups. Even in the cohort of patients with positive methylergonovine testing, mean late HMR was within the normal range. Our observations question whether HMR and WR in patients with VSA are truly significantly different than in healthy controls. Of note, several minor differences in imaging acquisition between this and other studies should be acknowledged such as the use of different collimators and radioactive compounds.

RDN has been studied since 2008 for its potential to control blood pressure in patients with therapy resistant hypertension, in which increased SNS activity has been hypothesized to play an important role.26 Only very recently, the results of several sham-controlled randomized trials demonstrated that the therapy, conducted using a radiofrequency ablation catheter, might significantly decrease blood pressure.27 At the same time, a series of studies were conducted to assess potential pleiotropic effects of RDN.28,29 In the present study, we attempted to further extend these findings in a cohort of VSA patients without residual regular therapeutic options. Given the limited options in objectively assessing the severity of signs and symptoms of these patients, we decided to further study the effect of RDN by using 123I-MIBG imaging. We hypothesized that post-RDN, late HMR would increase and WR would decrease as compared to pre-RDN.23,25 However, 6 months post-RDN, we found no meaningful differences in both early and late HMR and WR. The latter thus again questions the role of the SNS in patients with VSA and the potential of RDN to decrease intra-cardiac sympathetic nerve activity.

Nevertheless, we found significant improvements in angina class and quality of life at 6 months along with a numerical decrease in BP. Following treatment with the Paradise ultrasound balloon catheter, mean systolic ambulatory blood pressure decreased with 9mmHg at 6 months. Although these figures did not reach statistical significance in the present small single-center study, the primary results of the RADIANCE SOLO trial assessing the safety and efficacy of the same device in a multicenter randomized sham-controlled setting showed a significant decrease in daytime 24h ABPM as compared to sham.30


There are several limitations that should be taken into account. First, results were based on a small pilot study (N = 10) and should be considered hypothesis generating. Using the results of the present study along with the findings of previous work by Arbab et al, a total of 70 patients would be needed to support that RDN results in a 20% increase in late HMR. Second, WR was calculated using one of the methods as described by Flotats et al.,31 in which we used the actual heart counts for calculating WR, instead of ratios. Third, while the positive finding of a significant reduction in angina class could be interpreted as promising, a potential placebo effect of the treatment cannot be ruled out. In the recently published sham-controlled ORBITA trial, a sham procedure was able to significantly improve at least 3 subscales of the SAQ in patients with stable angina and significant coronary artery disease.32 Fourth, anti-anginal drug regimen was changed in 7/10 of the patients [including an increase in nitrates (n = 1) and diltiazem (n = 1)]. The impact of medication on MIBG uptake should be taken into account. Jacobson et al. described that the MIBG uptake could be inhibited mostly by the use of beta-blockers such as labetalol. Less evidence is available on the MIBG-inhibitory effect by calcium channel blockers.33 Furthermore, we acknowledge the fact that half of the patients were still using selective beta-blockers that were deliberately continued mostly due to the presence of a myocardial infarction in the past; in patients (N = 3), beta-blockers were stopped or dosages changed during follow-up. However, also in patients in whom beta-blockers were either stopped or dosages were changed, no change in late HMR was found which was in line with results in patients without changes in drug regimen.

Finally, we cannot exclude the fact that apart from autonomic nervous system tone, multiple other alternative factors might play a role in triggering coronary spasms such as endothelial dysfunction or microvascular dysfunction.34,35

New Knowledge Gained

The results in our study are promising and might fuel future discussion on the potential use of RDN in patients with vasospastic angina. Larger, randomized trials are needed to demonstrate the value of 123I-MIBG imaging post-RDN in patients with VSA.


RDN resulted in significant improvements in angina class and quality of life at 6 months in patients with refractory vasospastic angina. RDN did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG.



Joost Daemen received institutional research support from Abbott Vascular, Medtronic, Boston Scientific, Acist, and Pie Medical as well as speaker and consultancy fees from Medtronic, Acist, and Pythagoras. Conflicts of interest for other authors are not declared.

Supplementary material

12350_2019_1598_MOESM1_ESM.pptx (1.1 mb)
Supplementary material 1 (PPTX 1124 kb)


  1. 1.
    Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med 1959;27:375-88.Google Scholar
  2. 2.
    Boudou N, Despas F, Van Rothem J, Lairez O, Elbaz M, Vaccaro A, et al. Direct evidence of sympathetic hyperactivity in patients with vasospastic angina. Am J Cardiovasc Dis 2017;7:83-8.Google Scholar
  3. 3.
    Yasue H. Role of autonomic nervous system in the pathogenesis of Angina Pectoris. Arch Mal Coeur Vaiss 1983;76:3-6.Google Scholar
  4. 4.
    Lanza GA, Pedrotti P, Pasceri V, Lucente M, Crea F, Maseri A. Autonomic changes associated with spontaneous coronary spasm in patients with variant angina. J Am Coll Cardiol 1996;28:1249-56.Google Scholar
  5. 5.
    Feyz L, Wijchers S, Daemen J. Renal denervation as a treatment strategy for vasospastic angina induced ventricular tachycardia. Neth Heart J 2017;25:596-7.Google Scholar
  6. 6.
    MacAlpin RN. Cardiac arrest and sudden unexpected death in variant angina: Complications of coronary spasm that can occur in the absence of severe organic coronary stenosis. Am Heart J 1993;125:1011-7.Google Scholar
  7. 7.
    Yasue H, Takizawa A, Nagao M, Nishida S, Horie M, Kubota J, et al. Long-term prognosis for patients with variant angina and influential factors. Circulation 1988;78:1-9.Google Scholar
  8. 8.
    Nishizaki M. Life-threatening arrhythmias leading to syncope in patients with vasospastic angina. J Arrhythm 2017;33:553-61.Google Scholar
  9. 9.
    Bottsilverman C, Heupler FA. Natural-history of pure coronary-artery spasm in patients treated medically. J Am Coll Cardiol 1983;2:200-5.Google Scholar
  10. 10.
    Betriu A, Pomar JL, Bourassa MG, Grondin CM. Influence of partial sympathetic denervation on the results of myocardial revascularization in variant angina. Am J Cardiol 1983;51:661-7.Google Scholar
  11. 11.
    Yoshida K, Inoue T, Hirakawa N, Node K. Endoscopic thoracic sympathectomy as a novel strategy for vasospastic angina refractory to medical treatments. J Cardiol 2008;52:49-52.Google Scholar
  12. 12.
    Carrio I. Cardiac neurotransmission imaging. J Nucl Med 2001;42:1062-76.Google Scholar
  13. 13.
    Donazzan L, Mahfoud F, Ewen S, Ukena C, Cremers B, Kirsch CM, et al. Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension. Clin Res Cardiol 2016;105:364-71.Google Scholar
  14. 14.
    Wakabayashi T, Nakata T, Hashimoto A, Yuda S, Tsuchihashi K, Travin MI, et al. Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death. J Nucl Med 2001;42:1757-67.Google Scholar
  15. 15.
    Carrio I, Cowie MR, Yamazaki J, Udelson J, Camici PG. Cardiac sympathetic imaging with mIBG in heart failure. JACC Cardiovasc Imaging 2010;3:92-100.Google Scholar
  16. 16.
    Mauri L, Kario K, Basile J, Daemen J, Davies J, Kirtane AJ, et al. A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs. Am Heart J 2018;195:115-29.Google Scholar
  17. 17.
    Yasue H, Touyama M, Shimamoto M, Kato H, Tanaka S. Role of autonomic nervous system in the pathogenesis of Prinzmetal’s variant form of angina. Circulation 1974;50:534-9.Google Scholar
  18. 18.
    Schwartz PJ, Stone HL. Tonic influence of the sympathetic nervous system on myocardial reactive hyperemia and on coronary blood flow distribution in dogs. Circ Res 1977;41:51-8.Google Scholar
  19. 19.
    Yasue H, Horio Y, Nakamura N, Fujii H, Imoto N, Sonoda R, et al. Induction of coronary-artery spasm by acetylcholine in patients with variant angina—possible role of the parasympathetic nervous-system in the pathogenesis of coronary-artery spasm. Circulation 1986;74:955-63.Google Scholar
  20. 20.
    Mohrman DE, Feigl EO. Competition between sympathetic vasoconstriction and metabolic vasodilation in canine coronary circulation. Circ Res 1978;42:79-86.Google Scholar
  21. 21.
    Sakata K, Shirotani M, Yoshida H, Kurata C. Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing. J Am Coll Cardiol 1997;30:370-6.Google Scholar
  22. 22.
    Patel AD, Iskandrian AE. MIBG imaging. J Nucl Cardiol 2002;9:75-94.Google Scholar
  23. 23.
    Taki J, Yasuhara S, Takamatsu T, Nakajima K, Tatami R, Ishise S, et al. Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with vasospastic angina. Eur J Nucl Med 1998;25:229-34.Google Scholar
  24. 24.
    Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, et al. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 1987;28:1625-36.Google Scholar
  25. 25.
    Arbab AS, Koizumi K, Takano H, Uchiyama G, Arai T, Mera K. Parameters of dynamic and static iodine-123-MIBG cardiac imaging. J Nucl Med 1995;36:962-8.Google Scholar
  26. 26.
    Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof-of-principle cohort study. Lancet 2009;373:1275-81.Google Scholar
  27. 27.
    Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 2018;391:2346-55.Google Scholar
  28. 28.
    Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012;59:901-9.Google Scholar
  29. 29.
    Jackson N, Gizurarson S, Azam MA, King B, Ramadeen A, Zamiri N, et al. Effects of renal artery denervation on ventricular arrhythmias in a postinfarct model. Circ Cardiovasc Interv 2017;10:e004172.Google Scholar
  30. 30.
    Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): A multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 2018;391:2335-45.Google Scholar
  31. 31.
    Flotats A, Carrio I, Agostini D, Le Guludec D, Marcassa C, Schafers M, et al. Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging 2010;37:1802-12.Google Scholar
  32. 32.
    Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, et al. Percutaneous coronary intervention in stable angina (ORBITA): A double-blind, randomised controlled trial. Lancet 2018;391:31-40.Google Scholar
  33. 33.
    Jacobson AF, Travin MI. Impact of medications on mIBG uptake, with specific attention to the heart: Comprehensive review of the literature. J Nucl Cardiol 2015;22:980-93.Google Scholar
  34. 34.
    Bugiardini R, Pozzati A, Ottani F, Morgagni GL, Puddu P. Vasotonic angina: A spectrum of ischemic syndromes involving functional abnormalities of the epicardial and microvascular coronary circulation. J Am Coll Cardiol 1993;22:417-25.Google Scholar
  35. 35.
    Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: A changing philosophy. JAMA 2005;293:477-84.Google Scholar

Copyright information

© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Lida Feyz
    • 1
  • Maureen Henneman
    • 2
  • Fred Verzijlbergen
    • 2
    • 3
  • Isabella Kardys
    • 1
  • Nicolas M. Van Mieghem
    • 1
  • Joost Daemen
    • 1
    Email author
  1. 1.Department of CardiologyThoraxcenter, Erasmus Medical CenterCA RotterdamThe Netherlands
  2. 2.Department of Radiology and Nuclear MedicineErasmus Medical CenterRotterdamThe Netherlands
  3. 3.Department of Radiology and Nuclear MedicineRadboud University Medical CenterNijmegenThe Netherlands

Personalised recommendations