For Personal Use Only
Vol. 23, No. 10, October 2011 401
Changes in Radial Artery Volume Assessed Using Intravascular
Ultrasound: A Comparison of Two Vasodilator Regimens in
Transradial Coronary Interventions
Xavier Carrillo, MD1-3, Eduard Fernandez-Nofrerias, MD1, Francesco Ciompi2, Oriol Rodriguez-Leor, MD1-3, Petia
Radeva, PhD3, Neus Salvatella, MD1, Oriol Pujol, PhD2, Josepa Mauri, MD, PhD1, Antoni Bayes-Genis, MD, PhD1-3
ABSTRACT: Objectives. This study used intravascular ultra-
sound (IVUS) to evaluate radial artery volume changes after intra-
arterial administration of nitroglycerin and/or verapamil. Back-
ground. Radial artery spasm, which is associated with radial artery
size, is the main limitation of the transradial approach in percutane-
ous coronary interventions (PCI). Methods. This prospective, ran-
domized 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 in-
sertion) 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 seg-
mentation 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. Ad-
ministration 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
Use of the transradial approach (TRA) in the field of percu-
taneous 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 discom-
fort for the patient during the procedure and limits catheter
movement, leading to transradial failure and ultimately neces-
sitating alternative arterial access.
In order to reduce RS during catheter manipulation, various
drugs with vasodilating properties (alone or in combination)
have been evaluated in PCI5,7-11 and in cardiac surgery.12 De-
spite 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 com-
monly used vasodilator regimens using automatic volume quanti-
fication 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 ad-
ministration of 0.2 mg of nitroglycerin plus 2.5 mg of vera-
pamil (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 bradi-
cardia <45 bpm, advanced atrio-ventricular block, and reduced
left ventricular ejection fraction ≤35%. The study complied
with the Helsinki Declaration, and all patients provided writ-
ten 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 ra-
dial 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-vasodila-
tor 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
From 1the Cardiology Service, Hospital Universitari Germans Trias i Pujol, 2Com-
puter Vision Center, Universitat de Barcelona, and 3Department of Medicine, Univer-
sitat Autònoma de Barcelona, Barcelona, Spain.
Disclosure: The authors have completed and returned the ICMJE Form for Dis-
closure 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, Cardi-
ology Service, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n
08916. Badalona (Barcelona). Email: firstname.lastname@example.org
401-404_JIC1011_Carrillo.indd 4019/26/11 10:35 AM
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402 The Journal of Invasive Cardiology
CARRILLO, et al.
used for the automatic segmentation of luminal borders in lon-
gitudinal 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 (in-
side 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 classi-
fied 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 polynomi-
al 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 sequenc-
es 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 vari-
ables as mean and standard deviation or by me-
dian 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 com-
pared 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.
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
The volume and diameter of the radial arter-
ies measured in both groups at baseline and after
treatment are shown in Table 2. There were no sig-
nificant differences between baseline artery volumes
for each group. After vasodilator treatment, we ob-
served 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).
Figure 1. ECOC-RF results. Intravascular ultrasound of the radial artery with lon-
gitudinal reconstruction and detection of the luminal border in the same patient. (A)
Baseline evaluation. (B) Post-vasodilator treatment evaluation. Both longitudinal
(A1-B1) and ECOC-RF three-dimensional reconstructions (A2-B2) are shown.
Figure 2. Changes in the volume of individual radial arteries measured using intra-
vascular ultrasound at baseline and 5 minutes post-treatment. Group 1: nitroglycerin
plus verapamil; Group 2: verapamil alone.
401-404_JIC1011_Carrillo.indd 402 9/26/11 10:35 AM
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2.9 ± 0.62.9 ± 0.5
6.6 ± 6.78.6 ± 14.5
Vol. 23, No. 10, October 2011403
Radial Artery Volume Using Two Vasodilator Regimens
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 pa-
tients’ prior intervention histories, we found no significant dif-
ferences between patients with a prior PCI and those with no
previous PCI using the same radial access.
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 arte-
rial lumen volume after vasodilator treatment. Previous stud-
ies have used angiography8,11 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 in-
traluminal radial artery volume. Volume
assessment using the arterial diameter by
angiography is suboptimal, since it is a
two-dimensional extrapolation of a three-
To our knowledge, only one published
study has assessed the radial artery using
IVUS;15 in contrast to our study, that evalu-
ation was carried out using the intravascular
area to measure the size of the radial artery.
The application of an algorithm for the au-
tomatic 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 mea-
surement 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 angiography8,11 or
transcutaneous ultrasound.14 The increase in
radial artery volume has important implications
for transradial interventional cardiology: it al-
lows interventions to be performed in patients
with smaller radial arteries, decreases patient
discomfort during TRA, and allows transra-
dial PCI to be performed with larger catheters,
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 interven-
tion. 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 indepen-
dent 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
Table 1. Baseline patient characteristics.
(n = 30)
63 ± 12
(n = 15)
65 ± 10
(n = 15)
62 ± 12
Peripheral vascular disease
Body surface area
81 ± 15
166 ± 8
1.93 ± 0.20
29 ± 6
80 ± 13
167 ± 7
1.93 ± 0.17
30 ± 8
82 ± 18
166 ± 10
1.94 ± 0.23
29 ± 4
Group 1 = nitroglycerin plus verapamil; Group 2 = verapamil alone. Data given as n (%) or mean ±
Table 2. Radial artery measurements using intravascular ultrasound.
(n = 15)
451 ± 177
508 ± 192
58 ± 56
14 ± 15
2.7 ± 0.5
(n = 15)
456 ± 188
509 ± 170
53 ± 60
20 ± 37
2.7 ± 0.6
Baseline volume (mm3)
Post-treatment volume (mm3)
Absolute volume increase (mm3)
Relative volume increase (%)
Baseline diameter (mm)
Post-treatment diameter (mm)
Relative diameter increase (%)
Group 1: nitroglycerin plus verapamil; Group 2: verapamil alone. Data given as mean ± SD.
401-404_JIC1011_Carrillo.indd 4039/26/11 10:35 AM
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404 The Journal of Invasive Cardiology
CARRILLO, et al.
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 treat-
ment5,7-11,14 in the prevention of RS in transradial PCI; how-
ever, the ideal treatment has not been established. In this study,
we did not observe significant differences in arterial lumen vol-
ume 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 administra-
tion of verapamil monotherapy would have the same beneficial
effect as verapamil plus nitroglycerin, eliminating the systemic
vasodilating effect that nitroglycerin can cause. Indeed, the ad-
ministration 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 ma-
jority of patients, the systemic effect of nitroglycerin is insig-
nificant, but in some cases, such as patients with severe aortic
stenosis or systemic arterial hypotension, it can be important.
Evaluation of radial artery volume using IVUS and auto-
matic detection of the arterial lumen is feasible, sensitive, and
precise. Administration of nitroglycerin plus verapamil or vera-
pamil 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.
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