THE EFFECT OF DIFFERENT TYPE ROENTGEN CONTRAST MEDIA ON CARDIAC
ELECTROPHYSIOLOGY DURING CARDIAC ANGIOGRAPHY
ARSLAN OCAL¹
CEMAL OZBAKIR¹
Akay Hospital, Department of Cardiology, Ankara, Turkey¹
Short Title: The elecrophysiological effects of contrast agents
Contact Information
Dr. Arslan OCAL
Akay Hastanesi Kardiyoloji Bölümü, Ankara, Turkiye
Fax: ( +90) 2130202
Phone: ( +90) 312 416 50 50
E-mail: lion-144@hotmail.com
Objectives:
The contrast agents induced electrophysiological affects involve regional disturbances
of depolarization and repolarization, thereby causing disturbance of impulse conduction as
well as dispersion of refractoriness. The aim of this study is to define elecrophysiological
effects of four different contrast agents using effect on QT, QTc, QTd and signal averaged
ECG parameters.
Methods and Results:
The study population consisted of 96 subjects (61 male, 35 female, age 57,9  9,2
years ) who underwent standard coronary angiography and left ventriculography with stable
angina pectoris. Pre and postprocedural QT, QTc, QTd, filtered QRS duration and, RMS40
were compared. Low osmolar ionic (ioxaglate, group 1), low osmolar nonionic (iopamidol,
group2 and iobitridol, group3), isosmolar nonionic dimer (visipaque,group4) groups were not
statistically different according to age, gender, left ventricular volume, ejection fraction,
amount of contrast agent, jeopardy score). In group1; QT (403.5±41.6 to 427.4±38.3, p<0.001
), QTc(440.4±28.8 to 476.5±47.4, p<0.001 ), QTd(34.0±11.6 to 52.6±19.2, p<0.001), in
group2; QT(403.1±33.2 to 415.3±36.6, p=0.003), in group4; QTd(35.2±12.1 to 48.1±27.9,
p=0.013 ) were significantly changed. No other signal averaged ECG parameters were
changed.
Conclusion:
The electrophysiological alterations induced by contrast agents used in coronary angiography
can be determined by QT, QTc and QT dispersion but not signal avaraged ECG parameters.
Keywords: contrast agent, arrhythmia, signal averaged electrocardiography
Introduction
The coronary angiography (CAG) is the most commonly used diagnostic method for
coronary artery disease and have a mortality risk that is 0.11%. There are some complications
like contrast media induced arrhythmia (0.38%), hemodynamic complications(0.26%), and
allergic contrast reactions (0.37%) in coronary angiography. Contrast agents affect normal
cardiac electrophysiology when injected into coronary arteries. The contrast agents induced
electrophysiological
affects
involve
regional
disturbances
of
depolarization
and
repolarization, thereby causing disturbance of impulse conduction as well as dispersion of
refractoriness (1). A number of studies with diatrizoate that is one of ionic hiperosmolar
contrast medium have documented electrocardiographic changes such as arrhythmia and
conduction abnormalities (2, 3). Ventricular tachycardia and ventricular fibrillation occure
with using hiperosmolar contrast agent in coronary angiography ( 0.1-1.3%) (2, 4, 5, 6)
Hexabrix320 (ioxaglate) is low osmolar ionic contrast agent and nonionic low osmolar
contrast agents that of Visipaque320 (iodixanol), Iopamiro370 (iopamidol), Xenetix350
(iobitridol) are commonly used in our clinic. Routine electrocardiographic parameteres such
as PR interval, QT interval and QTc have been used as arrhythmia predictors in recent studies
but signal averaged electrocardiography (SAECG) not used (3, 4, 5, 6).
The aim of this study is to define elecrophysiological effects of four different contrast
agents using effect on QT, QTc, QT dispersion derived from 12 derivation ECG and signal
averaged ECG parameters.
Materials and Methods
The study population consisted of 96 subjects (61 male, 35 female; 57.9±9.2) who
underwent standard coronary angiography and left ventriculography with stable angina
pectoris at Catheter Laboratory of Gaziosmanpasa University School of Medicine Hospital
were included this study between 2005 June -2006 May. The patients who have had diabetes
mellitus, severe renal and hepatic disease, acute coronary syndrome, recent myocardial
infarction, history of percutaneous coronary interventions, severe pulmonary hypertension,
significant valvular disease, permanent pacemaker, bundle brunch block, atrial fibrillation,
and using antiarrhythmic drugs were excluded from study. The inform consent had been
obtained from all patients.
The patients were randomized a single-blind manner to Hexabrix, Xenetix, Iopamiro
and Visipaque were used respectively for each patient in coronary angiography. Coronary
angiography was performed with the Judkins technique, injecting about 7 ml of contrast agent
into the left coronary artery and about 5 ml into right coronary artery for each injection. 4±1
injection was used for left coronary artery imaging and 2±1 injection was used for right
coronary arteriography. Left ventriculography was performed using 0,5 ml/kg contrast agent
and no premedication was given before.
SAECG and ECG data of these patients were collected in recordings that obtained preprocedural (5 minutes) and post-procedural (5 minutes) 12 derivation ECG and signal
averaged ECG patterns. We detected late potentials in the terminal QRS complex from
orthogonal, bipolar XYZ ECG leads recordings by signal processing system use time domain
analysis. This system use 40 Hz high pass filter. Criteria for late potentials ( use of a 40 Hz
high pass bidirectional filter) are 1) filtered QRS complex; 114 to 120 ms, 2) less than 20 μV
of root-mean-square signal amplitude in the last 40 ms of filtered QRS complex, and 3) the
terminal filtered QRS complex remain below 40 μV for longer than 39 ms were used (7).
RMS40 and QRS time are achieved in SAECG recordings. The ECG intervals such as QT
interval, corrected QT time (QTc) were measured automatically. QT dispersion (QTd)
(maximum QT interval minus minimum QT interval) for a single 12-lead ECG was measured
manually.
Transthorasic echocardiography was performed using a 2.5 MHz transducer. All
measurements were performed following the American Society of Echocardiography’s
recommendations (8).
Statistical Analysis
All continuous variables were analysed with Kolmogorov-Smirnov test. Comparison of
between groups with regard to continuous variables were used one-way ANOVA. The paired
sample t-test was used to determine whether there was a difference between ECG and SAEG
variables recorded in each groups at before and after CAG. Multivariate two way repeated
measures ANOVA was used to comparison of changes on variables in groups with respect to
before and after CAG. Pairwise comparison test (LSD) were used for significant difference on
QTc variable at result of test. The categorical variables in four groups were compared using
chi-square test. The continuous variables are expressed as mean values±SD, and the discrete
variables as absolute values and percentages. A p-value <0,05 was considered significant.
Analyses were performed using commercially available software (SPSS Inc, Chicago,
Illinois).
Results
The patients were divided to four groups as group1 (Hexabrix, 23 patients, 14 male),
group2 (Xenetix, 32 patients, 25 male), group3 (Iopamiro; 20, 8 male) and group4 (Visipaque,
21 patients, 14 male).
Low osmolar ionic (hexabrix, group 1), low osmolar nonionic (iopamiro,group2 and
xenetix, group3 ), isosmolar nonionic (visipaque, group4) groups were not statistically
different according to age, left ventricular ejection fraction (LVEF), arterial blood pressure
(BP), amount of contrast agent, and diffuseness of coronary artery diseases (evaluated by
jeopardy score (9)). There was a significant difference between groups with respect to
LVEDP (11.9±2.3; 10.4±2.2; 12.2±4.2; 14.2±6.9, respectively; p=0.028) ( Table1).
Tablo1. Comparison of groups with respect to age, amount of contrast agent, BP, LVEDP,
LVEF and Jeopardy score
Age
Amount of Contrast
Agent (ml)
BP(mmHg)
LVEDP(mmHg)
Jeopardy score
LVEF(%)
Group1(n=23) Group2(n=32) Group3(n=20) Group4(n=21) F
p
(Hexabrix)
(Xenetix)
(Iopamiro)
(Visipaque)
57.0±10.3
57.1±9.5
59.4±8.9
58.9±7.7
0.41 0.746
108.9±57.9
105.5±32.6
87.2±14.1
107.4±35.4
1.31 0.278
149.5±21.7
11.9±2.3
1.1±1.4
63.8±16.5
145.9±21.4
10.4±2.2
1.2±1.4
61.0±16.3
156.1±25.2
12.2±4.2
1.7±1.8
67.4±12.1
148.2±23.0
14.2±6.9
1.5±2.0
57.9±20.4
0.75
3.18
0.56
1.11
0.526
0.028
0.645
0.350
No significant difference was founded with respect to gender (χ2=5.96; p=0.114) and
localization and severity of atherosclerotic lesion between groups (Table2).
Table 2. Comparison of groups with respect to gender and coronary atherosclerotic lesion
Gender Male
Female
RCA
Normal
Lesion <%70
≥%70
%100
CX
Normal
Lesion <%70
≥%70
%100
LAD
Normal
Lesion <%70
≥%70
%100
Group1(n=23) Group2(n=32) Group3(n=20) Group4(n=21)
χ2
p
(Hexabrix)
(Xenetix)
(Iopamiro)
(Visipaque)
14(60.9%)
25(78.1%)
8(44.4%)
14(66.7%)
5.96 0.114
9(39.1%)
7(21.9%)
10(55.6%)
7(33.3%)
11(47.8%)
12(37.5%)
7(37.9%)
13(61.9%)
5(21.7%)
12(37.5%)
6(33.3%)
4(19.0%)
5.72 0.767
5(21.7%)
6(18.8%)
4(22.2%)
4(19.0%)
2(8.7%)
2(6.3%)
1(5.6%)
0(0%)
13(56.5%)
20(62.5%)
12(66.7%)
15(71.4%)
4(17.4%)
6(18.8%)
2(11.1%)
2(9.5%)
3.20 0.956
5(21.7%)
4(12.5%)
3(16.7%)
2(9.5%)
1(4.3%)
2(6.3%)
1(5.6%)
2(9.5%)
10(43.5%)
16(50.0%)
7(38.9%)
8(38.1%)
8(34.8%)
8(25.0%)
3(16.7%)
4(19.0%)
7.10 0.627
4(17.4%)
7(21.9%)
7(38.9%)
6(28.6%)
1(4.3%)
1(3.1%)
1(5.6%)
3(14.3%)
In group1; QT (403.5±41.6 to 427.4±38.3, p<0.001 ), QTc(440.4±28.8 to 476.5±47.4,
,p<0.001), QTd(34.0±11.6 to 52.6±19.2, p<0.001), in group2; QT(403.1±33.2 to 415.3±36.6,
p=0.003 ), in group4; QTd(35.2±12.1 to 48.1±27.9, p=0.013) were significantly changed.
There was a significant difference wiht respect to QTc change values between groups
(p=0.005) and we found that Hexabrix is cause of this result (p=0.042) by using pairwise
comparison test. No significant changes on filtered QRS time (p=0.908) and RMS40
(p=0.438) values (Table 3).
Table 3. ECG and SAECG changes in groups by coronary angiography
Group1(n=23)
(Hexabrix)
403.5±41.6
427.4±38.3
(t=4.08,p<0.001)
Group2(n=32)
(Xenetix)
403.1±33.2
415.3±36.6
(t=3.25,p=0.003)
Group3(n=20)
(Iopamiro)
393.9±34.1
402.2±32.1
(t=1.36,p=0.191)
Group4(n=21)
(Visipaque)
397.1±51.9
402.8±46.0
(t=1.45,p=0.162)
F
p
0.29
2.06
0.42*
0.830
0.111
0.741
QT(msec)
Before
After
QTc(msec)
Before
After
440.4±28.8
476.5±47.4
(t=4.25,p<0.001)
443.1±26.6
442.2±28.2
(t=0.26,p=0.795)
440.6±22.1
440.6±26.2
(t=0.00,p=1.000)
440.5±39.1
449.5±44.3
(t=1.51,p=0.145)
0.06
4.65
2.83*
0.982
0.005
0.042**
QTd(msec)
Before
After
34.0±11.6
52.6±19.2
(t=4.83,p<0.001)
39.1±14.0
42.5±15.7
(t=1.61,p=0.118)
35.6±11.0
40.6±15.1
(t=1.49,p=0.155)
35.2±12.1
48.1±27.9
(t=2.74,p=0.013)
0.87
1.72
0.60*
0.461
0.169
0.618
RMS40
(μv)
Before
After
39.6±32.6
30.8±26.1
(t=1.15,p=0.261)
30.1±27.7
27.8±28.7
(t=0.58,p=0.565)
19.2±17.1
20.3±21.5
(t=0.25,p=0.806)
21.6±27.7
24.8±26.1
(t=0.57,p=0.576)
2.42
0.60
0.92*
0.071
0.619
0.438
Filtered
QRS Time
(msec)
Before
After
101.4±30.4
115.6±26.1
110.7±21.2
109.9±20.5
106.3±23.1
111.5±26.7
112.8±23.8
103.1±19.5
0.99
1.11
0.402
0.351
(t=1.65,p=0.112)
(t=0.17,p=0.863)
(t=0.73,p=0.475)
(t=1.14,p=0.266)
0.18*
0.908
* For Repeated Measures ANOVA test values
** Pairwise comparisons result: There was significant diference in Hexabrix group
(p<0.05).
Discussion
In recent studies have showed that hiperosmolar contrast agents had more adverse
effects than low osmolar and arrhythmic complication risk increase using contrast agents (10,
11, 12, 13, 14). Contrast agents possess an undesirable ability to prolong cardiac
repolarization that can be objectively measured as prolongation of the QTc on the ECG and
lead to serious arrhythmias such as ventricular fibrillation (15, 16, 17, 18).
Popio KA et al. considered that the electrophysiologic effects of contrast agents is
related to hiperosmolality (19). The osmolality is an important but not only one factor on
electrophysiologic effects of contrast agents. There are some studies which showed that the
ionic composition was responsible for this effect (20, 21, 22, 23, 24, 25). Wisneski JA et al.
reported that Hexabrix (ionic)
prolonged QT interval significantly, altough Iopamiro
(nonionic) had no significant changes (26). We demonstrated that there were significant
changes on QT (p<0.001) and QTc (p<0.001) values in group1 (Hexabrix) and QT interval
changes in group2 (Xenetix) group (p=0.003). No significant changes on QT and QTc time
were observed in other nonionic (Iopamiro, Visipaque) groups.
QT dispersion (QTd) as an index of the spatial dispersion of the ventricular recovery
times and it was proposed that the different ECG leads magnify the ECG signal of the
different myocardial regions. QTd is an almost direct measure of heterogeneity myocardial
repolarization and noninvasive predictor of arrhythmia. Abnormally high QT dispersion has
been correlated with risk of arrhythmic death in a variety of disorders. QTd also has been
correlated with efficacy and proarrhythmic potential of drug therapy (27). Literature reviews
found the QTd to vary mostly between 30 and 60 ms in normal subjects (28). The effects of
contrast agents on QTd were not examinated in recent trials. In our study, there were
signaficant changes on QTd values in group 1 (34.0±11.6 to 52.6±19.2 p<0.001) and group
4(35.2±12.1 to 48.1±27.9 p=0.013) but this cahanges in normal range.
The presence of a late potential is a sensitive, but not specific marker of arrhythmic risk
and thus its prognostic use is limited (27). Our findings showing that ionic and nonionic
contrast agents have not effect on SAECG parameters. This result may related to limitation of
late potential analysis is the absence of information about ventricular repolarization.
Conclusion
The electrophysiological alterations induced by contrast agents used in coronary
angiography can be determined by QT, QTc and QT dispersion by using standart 12derivation ECG but not signal avaraged ECG parameters. Different type contrast agents
makes different electrophysiological effect determined by standart ECG. We considered that
this electrophsyological effects of contrast agents is related to be ionic. The most effect on
electrophysiological parameters was occured by ioxaglate. Clinical results of this
electrophysiological alterations needs to be evaluated further.
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