Changes in Radial Artery Volume Assessed Using Intravascular Ultrasound: A Comparison of Two Vasodilator Regimens in Transradial Coronary Interventions

Abstract: Objectives. This study used intravascular ultrasound (IVUS) to evaluate radial artery volume changes after intra-arterial administration of nitroglycerin and/or verapamil. Background. Radial artery spasm, which is associated with radial artery size, is the main limitation of the transradial approach in percutaneous coronary interventions (PCI). Methods. This prospective, randomized study compared the effect of two intra-arterial vasodilator regimens on radial artery volume: 0.2 mg of nitroglycerin plus 2.5 mg of verapamil (Group 1; n = 15) versus 2.5 mg of verapamil alone (Group 2; n = 15). Radial artery lumen volume was assessed using IVUS at two time points: at baseline (5 minutes after sheath insertion) and post-vasodilator (1 minute after drug administration). The luminal volume of the radial artery was computed using ECOC Random Fields (ECOC-RF), a technique used for automatic segmentation of luminal borders in longitudinal cut images from IVUS sequences. Results. There was a significant increase in arterial lumen volume in both groups, with an increase from 451 ± 177 mm³ to 508 ± 192 mm³ (p = 0.001) in Group 1 and from 456 ± 188 mm³ to 509 ± 170 mm³ (p = 0.001) in Group 2. There were no significant differences between the groups in terms of absolute volume increase (58 mm³ versus 53 mm³, respectively; p = 0.65) or in relative volume increase (14% versus 20%, respectively; p = 0.69). Conclusions. Administration of nitroglycerin plus verapamil or verapamil alone to the radial artery resulted in similar increases in arterial lumen volume according to ECOC-RF IVUS measurements.

J INVASIVE CARDIOL 2011;23(10):401–404

Key words: radial, vasodilator treatment, percutaneous coronary intervention, IVUS, volumetric IVUS analysis

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Use of the transradial approach (TRA) in the field of percutaneous coronary intervention (PCI) has increased substantially in recent years.¹ Compared with the traditional transfemoral approach, the main advantage of TRA is its association with a lower incidence of cardiovascular complications.^2,3 In contrast, one of its main limitations is that the radial artery has a highly developed muscular layer with vasoreactive properties⁴ and is significantly smaller in size.

Radial spasm (RS) is one of the main complications of radial artery catheterization. The incidence of RS varies from 3.8% to 20%, depending on the definition utilized.^5,6 RS causes discomfort for the patient during the procedure and limits catheter movement, leading to transradial failure and ultimately necessitating alternative arterial access.

In order to reduce RS during catheter manipulation, various drugs with vasodilating properties (alone or in combination) have been evaluated in PCI^5,7-11 and in cardiac surgery.¹² Despite these studies, the ideal treatment for preventing RS has not been established.

The objective of this study was to evaluate the extent of radial vasodilation induced by intra-arterial administration of two commonly used vasodilator regimens using automatic volume quantification of the radial artery with intravascular ultrasound (IVUS).

Patients and Methods

The study included 30 consecutive patients who required PCI. Patients were randomized 1:1 to receive intra-arterial administration of 0.2 mg of nitroglycerin plus 2.5 mg of verapamil (Group 1) or 2.5 mg of verapamil alone (Group 2) into the radial artery. Both the physicians performing the procedure (EF-N, OR-L, JM) and the research team that analyzed the volumes obtained by IVUS (FC, PR, OP) were blinded to the patient’s study group. Exclusion criteria included sinus bradicardia <45 bpm, advanced atrio-ventricular block, and reduced left ventricular ejection fraction ≤35%. The study complied with the Helsinki Declaration, and all patients provided written informed consent prior to the procedure.

The intervention using TRA was carried out with a 6 Fr, 10 cm hydrophilic introducer catheter (Radiofocus Introducer II, Terumo Corporation). Five minutes after sheath insertion, a first radial artery analysis was performed using a pullback IVUS (Atlantis^™ SR Pro, 40 MHz, Boston Scientific) through the radial sheath (baseline time point). Next, patients were treated with their assigned vasodilator regimen (nitroglycerin and/or verapamil diluted in 15 ml of saline) into the radial artery; after 1 minute, a second IVUS study was carried out (post-vasodilator time point). Both pullbacks were performed automatically with a constant velocity using a disposable MD5 Pullback Sled (Boston Scientific) and evaluated at least 75 mm of radial artery proximal to the end of the introducer.

The luminal volume of the radial artery was computed by applying ECOC Random Fields (ECOC-RF), a technique used for the automatic segmentation of luminal borders in longitudinal cut images from IVUS sequences.¹³ ECOC-RF is a multiclass classification framework that exploits the contextual information on an IVUS image to define the blood region (inside the intima) in the longitudinal view of the vessel. In order to segment the blood region, a longitudinal view of the artery is extracted from the sequence of IVUS images by selecting a certain cut angle. A set of textural features are then extracted from the longitudinal image and classified by a set of context-based binary classifiers in the Framework of Error-Correcting Output Codes (see reference 13 for details). The lumen border is then defined by applying an active contour model of the blood region defined by the classification technique.

In order to compute the lumen volume along the whole vessel, four longitudinal views are extracted at 0, 45, 90, and 135 degree angles. The ECOC-RF technique is then applied to the four images and a set of eight points defining the lumen area in the short axis image is obtained. The lumen area for each frame of the sequence is then obtained by interpolating the eight points by a set of polynomial functions (spline). The lumen volume is finally computed as the sum of all lumen areas (Figure 1).

Using ECOC-RF, we calculated the intraluminal volume of the radial arteries in both IVUS sequences before and after administration of the vasodilator regimens. The change in arterial lumen volume was compared in the two groups.

Statistical analysis. Dichotomous variables are reported as percentages and quantitative variables as mean and standard deviation or by median and interquartile range. For non-normally distributed variables, dichotomous variables were compared using Fisher’s exact test. Volume changes after intra-arterial vasodilator treatment were evaluated by a comparison of paired data using the Wilcoxon test, and the percentage of variation in radial volume was recorded. We compared the radial volumes of the two groups using the Mann Whitney U test. Statistical analysis was performed using the statistical software package SPSS version 15 (SPSS Inc.). p-values <0.05 were considered statistically significant.

Results

Of the 30 patients included in the study, 15 were randomized to Group 1 (nitroglycerin plus verapamil) and 15 were randomized to Group 2 (verapamil alone). The baseline characteristics of the study patients are shown in Table 1. There were no significant differences in the characteristics of the two groups.

The volume and diameter of the radial arteries measured in both groups at baseline and after treatment are shown in Table 2. There were no significant differences between baseline artery volumes for each group. After vasodilator treatment, we observed a significant increase in arterial lumen volume in both treatment groups (from 451 ± 177 mm³ to 508 ± 192 mm³ [p <0.01] in Group 1 and from 456 ± 188 mm³ to 509 ± 170 mm³ [p <0.01] in Group 2), as well as a significant increase in radial diameter (from 2.7 mm to 2.9 mm [p <0.01] and from 2.7 mm to 2.9 mm [p <0.01], respectively).

There were no significant differences in the radial volume increases (both relative and absolute) or diameters between the two vasodilator treatment groups. Figure 2 shows the changes in radial artery baseline volume and post-vasodilator treatment volume in the arteries of individual patients in both groups.

Analyzing the increase in volume with respect to the patients’ prior intervention histories, we found no significant differences between patients with a prior PCI and those with no previous PCI using the same radial access.

Discussion

IVUS with automatic detection of arterial lumen (ECOC-RF) is a precise method for calculating radial artery volume and is also a highly sensitive way to measure differences in arterial lumen volume after vasodilator treatment. Previous studies have used angiography^8,11 or transcutaneous ultrasound¹⁴ to evaluate the effect of vasodilator drugs on the radial artery. Direct visualization of the arterial lumen using IVUS is the most sensitive method for evaluating intraluminal radial artery volume. Volume assessment using the arterial diameter by angiography is suboptimal, since it is a two-dimensional extrapolation of a three-dimensional phenomenon.

To our knowledge, only one published study has assessed the radial artery using IVUS;¹⁵ in contrast to our study, that evaluation was carried out using the intravascular area to measure the size of the radial artery. The application of an algorithm for the automatic detection of the arterial lumen (i.e., ECOC-RF) allows the precise and reliable measurement of arterial volume. This type of assessment, which is more sensitive than those used in other studies, allows the measurement of small increases in volume that are not detected when evaluating the arterial diameter or area at a single point.

As demonstrated in previous studies, there are several vasodilator regimens that can achieve a significant increase in arterial volume, as measured using angiography^8,11 or transcutaneous ultrasound.¹⁴ The increase in radial artery volume has important implications for transradial interventional cardiology: it allows interventions to be performed in patients with smaller radial arteries, decreases patient discomfort during TRA, and allows transradial PCI to be performed with larger catheters, when required.

In contrast to other studies,¹⁵ we did not find significant differences in the radial artery diameter or in volume increases in patients with versus without previous transradial intervention. Using radial artery IVUS, Edmunson et al¹⁵ showed a smaller radial diameter in patients with a previous transradial intervention; however, the response to vasodilators was maintained, a finding that is consistent with what we observed in our study.

The main benefit of intra-arterial vasodilator medication is the prevention of RS. Fukuda et al¹⁶ demonstrated that the presence of RS is greater in smaller arteries, and others showed that an increase in radial artery size decreased RS.⁶ However, the relationship between increases in arterial lumen volume and decreases in RS is not linear. One study has shown that while certain drugs do not increase the arterial diameter, they have an effect on the incidence of RS during the procedure.⁸ This suggests a direct effect of the drug on RS that is independent of the change in radial volume. Others have reported that greater increases in arterial volume do not translate to a lower incidence of RS.¹¹ Moreover, Kiemeneij et al⁷ did not measure the lumen of the radial artery, but the force required to pull out the radial sheath, as an indirect indicator of the vasodilator activity of verapamil and nitroglycerin. In the context of these findings, we believe that the increase in arterial volume induced by vasodilator therapy could decrease RS by increasing radial artery volume, which could add to the direct effect of intra-arterial vasodilator medication in preventing RS.

Multiple studies have assessed intra-arterial vasodilator treatment^5,7-11,14 in the prevention of RS in transradial PCI; however, the ideal treatment has not been established. In this study, we did not observe significant differences in arterial lumen volume increases with the two intra-arterial treatment regimens used. Both groups showed arterial lumen volume increases that were significant and similar in magnitude. Given the similar effect on radial artery volume, we believe that the administration of verapamil monotherapy would have the same beneficial effect as verapamil plus nitroglycerin, eliminating the systemic vasodilating effect that nitroglycerin can cause. Indeed, the administration of both drugs could cause a significant pressure drop.^14,15 Verapamil should be used with caution in cases of severe bradycardia and left ventricular dysfunction. In the majority of patients, the systemic effect of nitroglycerin is insignificant, but in some cases, such as patients with severe aortic stenosis or systemic arterial hypotension, it can be important.

Conclusions

Evaluation of radial artery volume using IVUS and automatic detection of the arterial lumen is feasible, sensitive, and precise. Administration of nitroglycerin plus verapamil or verapamil monotherapy produces similar increases in radial artery volume. Future studies should clarify the clinical significance of increasing radial arterial lumen volume in terms of RS or the possibility of introducing larger catheters in daily practice.

References

1. Baz JA, Albarran A, Pinar E, Mauri J. Spanish cardiac catheterization and coronary intervention registry. 18th Official Report of the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (1990-2008). Rev Esp Cardiol. 2009;62(12):1418-1434.
2. Rao SV, Ou FS, Wang TY, et al. Trends in the prevalence and outcomes of radial and femoral approaches to percutaneous coronary intervention: a report from the national cardiovascular data registry. JACC Cardiovasc Interv. 2008;1(4):379-386
3. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J. 2009;157(1):132-140.
4. Sanmartin M, Goicolea J, Ocaranza R, Cuevas D, Calvo F. Vasoreactivity of the radial artery after transradial catheterization. J Invasive Cardiol. 2004;16(11):635-638.
5. Chen CW, Lin CL, Lin TK, Lin CD. A simple and effective regimen for prevention of radial artery spasm during coronary catheterization. Cardiology. 2006;105(1):43-47.
6. Ruiz-Salmeron RJ, Mora R, Velez-Gimon M, et al. Radial artery spasm in transradial cardiac catheterization. Assessment of factors related to its occurrence, and of its consequences during follow-up. Rev Esp Cardiol. 2005;58(5):504-511.
7. Kiemeneij F, Vajifdar BU, Eccleshall SC, Laarman G, Slagboom T, van der Wieken R. Evaluation of a spasmolytic cocktail to prevent radial artery spasm during coronary procedures. Catheter Cardiovasc Interv. 2003;58(3):281-284.
8. Ruiz-Salmeron RJ, Mora R, Masotti M, Betriu A. Assessment of the efficacy of phentolamine to prevent radial artery spasm during cardiac catheterization procedures: a randomized study comparing phentolamine vs. verapamil. Catheter Cardiovasc Interv. 2005;66(2):192-198.
9. Coppola J, Patel T, Kwan T, et al. Nitroglycerin, nitroprusside, or both, in preventing radial artery spasm during transradial artery catheterization. J Invasive Cardiol. 2006;18(4):155-158.
10. Varenne O, Jegou A, Cohen R, et al. Prevention of arterial spasm during percutaneous coronary interventions through radial artery: the SPASM study. Catheter Cardiovasc Interv. 2006;68(2):231-235.
11. Kim SH, Kim EJ, Cheon WS, et al. Comparative study of nicorandil and a spasmolytic cocktail in preventing radial artery spasm during transradial coronary angiography. Int J Cardiol. 2007;120(3):325-330.
12. Ustunsoy H, Kazaz H, Celkan MA, et al. Randomized comparison of vasodilator effects of iloprost versus diltiazem on flow and pathologic changes in radial arteries: mid-term angiographic control study of the comparison of vasodilators on radial artery vasospasm. Heart Surg Forum. 2009;12(4):E202-E207.
13. Ciompi F, Pujol O, Fernandez-Nofrerias E, Mauri J, Radeva P. ECOC random fields for lumen segmentation in radial artery IVUS sequences. Med Image Comput Comput Assist Interv. 2009;12(Pt 2):869-876.
14. Byrne J, Spence M, Haegeli L, et al. Magnesium sulphate during transradial cardiac catheterization: a new use for an old drug? J Invasive Cardiol. 2008;20(10):539-542.
15. Edmundson A, Mann T. Nonocclusive radial artery injury resulting from transradial coronary interventions: radial artery IVUS. J Invasive Cardiol. 2005;17(10):528-531.

16. Fukuda N, Iwahara S, Harada A, et al. Vasospasms of the radial artery after the transradial approach for coronary angiography and angioplasty. Jpn Heart J. 2004;45(5):723-731.

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From ¹the Cardiology Service, Hospital Universitari Germans Trias i Pujol, ²Computer Vision Center, Universitat de Barcelona, and ³Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted July 12, 2011, provisional acceptance given July 25, 2011, final version accepted August 5, 2011.
Address for correspondence: Antoni Bayes-Genis, MD, PhD, FESC, Chair, Cardiology Service, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n 08916. Badalona (Barcelona). Email: abayes.germanstrias@gencat.cat