Contemporary Analysis of Predictors and
Etiology of Ventricular Fibrillation During
Diagnostic Coronary Angiography
Jun Chen, MD; Li-Jian Gao, MD; Ji-Lin Chen, MD; Hui-Jun Song, MD
Address for correspondence:
Ji-Lin Chen, MD
Department of Cardiology
Fuwai Hospital and Cardiovascular
Institute Peking Union Medical
College and Chinese Academy
of Medical Sciences
Beijing, China
jilinchen@yahoo.com
Departments of Cardiology (Jun Chen, Gao, and JiLin Chen); Radiology (Song), Fuwai Hospital and
Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical
Sciences, Beijing, China
Objectives: To assess the incidence, investigate the predictors and analyze the causes of ventricular fibrillation
(VF) during coronary angiography (CA) on the condition of current techniques.
Methods: From April 2004 to January 2007, a total 22,254 patients (27,798 procedures) received CA procedures
in our center; 27 patients developed VF during CA. This report was to retrospectively analyze the clinical basic
characteristics, coronary angiographic characteristics and CA procedure records of these patients.
Results: The incidence of VF during CA was 0.097%. The incidence of VF in radial approaches and femoral
approaches was 0.076% and 0.147% (p = 0.085). The VF patients had higher coronary artery bypass grafting
(CABG) rates (11.1% vs 2.3%, p = 0.024) and were more likely to have a three-vessel disease (59.3% vs
31.2%, p = 0.002) and a total occlusion lesion (25.9% vs 11.1%, p = 0.014) than non-VF patients. On logistic
regression analysis, three-vessel disease (OR: 2.582, 95% CI: 1.165-5.720, p = 0.019) and the history of CABG
(OR: 3.959, 95% CI: 1.160-13.513, p = 0.028) were the two independent predictors of VF occurrences. Among
27 episodes of VF, 13 were ischemia-related; 11 were manipulation-related; two were contrast-related; one
was hypokalemia-related; and the causes remain unclear in five episodes.
Conclusions: The incidence of VF during CA is low on the condition of current techniques. The severity of
coronary artery disease (CAD) is an independent predictor of VF occurrence during CA. Acute ischemia and
inappropriate manipulation may be the two main causes in VF development.
Introduction
Although ventricular fibrillation (VF) during coronary
angiography (CA) has been recognized as a well-known
complication, our understanding about the incidence,
predictors and causes of VF during CA on the condition
of current techniques is little. Most studies about VF during
CA were published more than one decade ago. Early reports
showed that the VF during CA were not infrequent and were
mainly related to the use of contrast agents.1 – 7 In recent
years, with the use of new nonionic contrast agents, the
improvements of operator skills, and the widespread use of
small-sized catheters, we speculated that the incidence of VF
during CA might decrease and the proportion of causes of
VF might change. In this report, we retrospectively analyzed
the clinical data of a large group of patients undergoing CA
and tried to understand the incidence, predictor, and causes
of VF during CA on the condition of current techniques.
Methods
Patients
From April 2004 to January 2007, a total of 22,254 patients
(16,801 males, 5,453 females; mean age 57.4±11.1 years)
received 27,798 CA procedures in our center. Femoral
approaches were used in 6,269 patients with 8,163 procedures, and radial approaches were used in 15,985 patients
with 19,635 procedures. Radial approaches used a 5F or
Received: November 5, 2007
Accepted with revision: January 4, 2008
4F catheter, and femoral approaches used 6F and 7F
catheters. Nonionic contrast media Ultravist 370 (Schering,
GuangZhou, China) or Omnipaque (Nycomed, ShangHai,
China) were used for all patients undergoing CA. Patients
with acute myocardial infarction for direct percutaneous
coronary intervention (PCI) were not enrolled. Patients were
divided into VF and non-VF groups according to whether or
not they had VF during CA.
Date Collection and Definitions
This data collection was from the catheterization laboratory’s computerized database and medical records at our
center. We retrospectively analyzed the clinical basic characteristics, coronary angiographic characteristics and CA
procedure records of these patients.
All CA procedures were performed or monitored by 24
experienced operators who performed more than 500 CAs
each year. All VFs were diagnosed by 3-lead electrocardiogram (ECG) monitor. The cine angiograms, cardiograms
and medical records of every patient with VF were reviewed
by two experienced doctors.
A diseased coronary artery was defined as a ≥50% narrowing of the luminal diameter. We considered that the
episode of VF was associated with acute ischemia when
marked ST segment depression, catheter occlusion or coronary artery spasm was found before the onset of VA. If the
VF occurred during or less than 10 s after injection and some
Clin. Cardiol. 32, 5, 283–287 (2009)
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20394  2009 Wiley Periodicals, Inc.
283
Clinical Investigations
continued
typical ECG changes (such as bradycardia, QT interval prolongation, T-wave amplitude, rotation of the QRS axis, and
PR prolongation) were simultaneously observed before the
onset of VA, we considered that the VA was associated with
contrast medium toxicity.
Statistical Analysis
Quantitative variables were presented as mean±standard
deviation and categorical variables as percentages. The
Student’s t-test was used to compare the difference in
parametric data, and the chi-square analysis was used
to analyze the nonparametric data. Logistic regression
methods were used to calculate factor-adjusted odds ratios
and to determine the independent predictors of VF. We used
SPSS 11.5 (SPSS Inc., Chicago, III.) for statistical analysis. P
value less than 0.05 was considered statistically significant.
Results
The basic clinical characteristics, angiography characteristics, and the incidence of VF during CA of all patients are
listed in Table 1. From a total of 27,798 coronary angiographic procedures, there were 27 episodes (27 patients) of
VF in the cardiac catheterization laboratory. The VF developed during the right coronary artery (RCA) procedure in
16 patients, left coronary artery (LCA) procedure in eight
patients, bypass graft procedure in two patients, and after
the CA procedure (≤ 5 minutes) in one patient. Femoral
approaches were used in 6,269 patients with 8,163 procedures, and VF occurred in 12 procedures. Radial approaches
were used in 15,985 patients with 19,635 procedures, and VF
occurred in 15 procedures. The incidence rate of VF during
CA was 0.097%. The incidences of VF during RCA, LCA and
bypass graft angiography were 0.058%, 0.029% and 0.31%,
respectively. The incidences of VF in femoral approaches
and radial approaches were 0.147% and 0.076% (p = 0.085).
Of the 27 patients experiencing VF, 26 patients received
defibrillation within 1 min and were successfully returned to
sinus rhythm. One patient returned to sinus rhythm after a
thump-version. None of the 27 patients had any prior history
of VF or malignant arrhythmia and were discharged without
complications or reccurrence of VF during hospitalization.
Table 2 shows the basic clinical characteristics of the VF
and non-VF group. Patients developing VF during CA were
more likely to have a history of coronary artery bypass
grafting (CABG). There appears to be no relationship to the
other clinical characteristics that are listed in Table 2.
The coronary angiographic characteristics of the VF
group and non-VF group are shown in Table 3. Three-vessel
disease and total occlusion lesion were more common in the
VF group than in the non-VF group.
On a logistic regression analysis, three-vessel disease
and the history of CABG were two independent predictors
of VF occurrence. Table 4 presents the detailed results of
the logistic analysis.
284
Clin. Cardiol. 32, 5, 283–287 (2009)
J. Chen et al: Ventricular fibrillation during coronary angiography
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20394  2009 Wiley Periodicals, Inc.
Table 1. The Basic Clinical Characteristics, Angiography Findings and the
Incidence of Ventricular Fibrillation During Coronary Angiography in 22,254
Patients
Incidence of
Patients, n (%) VF during CA, (%)
Basic clinical characteristics
Men
16,801 (75.6)
0.099
7,565 (34)
0.089
4,829 (21.7)
0.116
514 (2.3)
0.466
History of PCI
4,315 (19.4)
0.075
Hypertension
12,306 (55.3)
0.098
Hypercholesterolemia
7,391 (33.2)
0.130
Diabetes mellitus
4,405 (19.8)
0.091
Smoking
10,213 (45.9)
0.094
Valvular heart diseases
890 (4)
0.090
Renal insufficiency
131 (0.6)
0
History of AMI
History of revascularization
History of CABG
Ejection fraction≤40%
2,026 (9.1)
0.119
Three-vessel disease
6,951 (31.2)
0.187
Two-vessel disease
4,852 (21.8)
0.083
Single-vessel disease
4,631 (20.8)
0.053
Roughly normal
5,830 (26.2)
0.046
Left main artery lesion
2,111 (9.5)
0.191
Total occlusion lesion
2,474 (11.1)
0.227
20,010 (89.9)
0.103
Coronary angiography characteristics
Right-dominant
Left-dominant
1,222 (5.5)
0
Balanced
1,022 (4.6)
0.079
Congenital anomalies
310 (1.4)
0
Abbreviations: VF, ventricular fibrillation; CA, coronary angiography;
AMI, acute myocardial infarction; CABG, coronary artery bypass grafting;
PCI, percutaneous coronary intervention.
The possible causes of VF during CA are shown in
Table 5. Most episodes of VFs were ischemia-related and
manipulation-related.
Discussions
Several large retrospective series had examined the incidence of VF during CA in the past. Early studies suggested
Table 2. Basic Clinical Characteristics of Coronary Angiography Patients
Developing and not Developing Ventricular Fibrillation
Table 3. Angiography Characteristics of Patients Developing and not
Developing Ventricular Fibrillation
VF (n = 27) 27
procedures
Non-VF
(n = 22,227)
27,771
procedures
P value
Coronary artery disease
57.9±10.7
57.4±11.1
>0.05
Men, %
77.8
75.5
History of AMI, %
29.6
History of
revascularization, %
VF
(n = 27) %
Non-VF
(n = 22,227) %
Three-vessel disease
59.3
31.2
>0.05
Two-vessel disease
18.5
21.8
>0.05
34
>0.05
Single-vessel disease
11.1
20.8
>0.05
25.9
21.7
>0.05
Roughly normal
11.1
26.2
>0.05
Left main artery lesion
18.5
9.5
>0.05
History of CABG, %
11.1
2.3
Total occlusion lesion
25.9
11.1
History of PCI, %
14.8
19.4
>0.05
Hypertension, %
55.6
55.3
>0.05
96.3
89.9
>0.05
Hypercholesterolemia, %
44.4
33.2
>0.05
Left-dominant
0
5.5
>0.05
Diabetes mellitus, %
18.5
19.8
>0.05
Balanced
3.7
4.6
>0.05
Smoking, %
44.4
45.9
>0.05
Congenital anomalies
0
1.4
>0.05
3.7
4.0
>0.05
Age, y
Valvular
heart diseases, %
Angiography
characteristics
0.024
Renal insufficiency, %
0
0.59
>0.05
Ejection fraction≤40%, %
11.1
9.1
>0.05
Abbreviations: VF, ventricular fibrillation; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.
an incidence of VF of 0.1%–0.4%.1 – 9 We observed VF in
0.097% of 27,798 CAs performed using current techniques.
The incidence of VF was lower than most of the previous studies. We considered the use of a new contrast
medium, the application of a smaller-sized catheter, and the
improvement of operator skills as main contributors to the
decrease in incidences.
Similar to previous study,10 the incidence of VF during
bypass graft angiography was higher, which was more than
five times that of RCA angiography and over ten times
that of LCA angiography in our data. Patients who had
a history of CABG tended to have more severe coronary
artery disease (CAD) in our center; we speculated that
CAD severity might be related to the episode of VF. In
addition, the higher incidence of VF might also result from
the relatively large volume of contrast material injected per
mass of perfused myocardium.
Although there was no statistical difference in incidence
of VF between radial and femoral approaches, a trend was
noted that the episodes of VF were more frequent in femoral
approaches than radial approaches. We speculated that
the use of a smaller-sized catheter might have contributed
P value
0.002
0.025
Coronary artery dominant
Right-dominant
Abbreviations: VF, ventricular fibrillation.
primarily to the decreased incidence of VF. On the one
hand, a smaller-sized catheter reduced the incidence of
catheter occlusion, which certainly brings about a reduction
in ischemia-induced VF; while on the other hand, the use
of a smaller-sized catheter tended to reduce the volume of
contrast material injections, which might also reduce the
occurrence of contrast-induced VF.
Comparing with angiography characteristics of VF group
and non-VF group, we found that patients developing VF
during CA were more likely to have a three-vessel disease
or a total occlusion lesion. On a logistic regression analysis,
three-vessel disease was the only angiography characteristic
that predicted the episodes of VF. Although previous studies
found that CAD lowered the threshold of VF,11 most of the
early reports suggested that the episodes of VF were not
related to the severity of CAD.3,5,12 Because of the use of
ionic contrast agents, a predominance of contrast-related
VFs were observed in previous studies, which might be
the main reason contributing to the observed difference
between previous and present studies.
The causes of VF during CA have been described
previously. Early reports3,5,10,12 suggested that although VF
could be caused by ischemia or mechanical complications,
almost all VF had been associated with contrast medium
toxicity and it was considered the main mechanism of VF
during CA. Although new contrast media associated with
a decreased risk of VF have been widely used in invasive
procedures in recent years,6,7,9,13 the current causes of VF
during CA have not been discussed comprehensively.
Clin. Cardiol. 32, 5, 283–287 (2009)
J. Chen et al: Ventricular fibrillation during coronary angiography
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20394  2009 Wiley Periodicals, Inc.
285
Clinical Investigations
continued
Table 4. Logistic Regression for Ventricular Fibrillation Occurrence
Factors
B
OR
95 (%) CI
P value
History of CABG
1.376
3.959
1.160–13.513
0.028
Three-vessel disease
0.948
2.582
1.165–5.720
0.019
Total occlusion lesion
0.824
2.279
0.948–5.481
0.066
Abbreviations: CABG, coronary artery bypass grafting.
Table 5. Possible Causes of Ventricular Fibrillation During Coronary
Angiography in 27 Patients
Possible causes of VF
Associated with acute ischemia
Patients (n)
13
Coronary artery spasm
1
Catheter occlusion
5
Contrast medium stagnation
1
Air injection
1
Others
3
Associated with manipulation
11
Impacted catheter
5
Catheter stimulation
1
Catheter superselective intubation
6
Catheter deep intubation
2
Long or vigorous injection
4
Associated with contrast toxicity
2
Associated with hypokalemia
1
Unclear causes
5
Abbreviations: VF, ventricular fibrillation; CA, coronary angiography.
Unlike most of the early studies, our data suggest that
acute ischemia has become an important cause of VF during
CA. This observation was supported by a recent report14 in
which a small caliber of RCA and associated ST segment
depression were recognized as important causes of VF
during coronary angioplasty. From our point of view, there
are three possible explanations for the observed differences
between our result and early reports. First, in our study, a
new, nonionic medium was used in all patients; this definitely
brought about a lower incidence of contrast-induced VF.
Second, all procedures were performed by highly skilled
operators in a high-volume interventional therapy center. It
was very possible to reduce the episodes of manipulationrelated VF. Third, 7F catheters were used in approximately
70% of the previous studies reported; we chose to perform
286
Clin. Cardiol. 32, 5, 283–287 (2009)
J. Chen et al: Ventricular fibrillation during coronary angiography
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20394  2009 Wiley Periodicals, Inc.
procedures in our center with a 5F catheter. The use of
smaller catheters also tended to reduce the incidence of
contrast-induced VF. All these certainly brought about a
change in proportion of causes. In addition, the mechanism
of acute ischemia could also help answer the question of
incidence of VF being higher during coronary angioplasty
than diagnostic angiography15 , and why there was a marked
discrepancy in the incidence of right and left CA. In our
opinion, acute ischemia played an important role in the
VF development during CA on the condition of current
techniques.
Apart from acute ischemia, inappropriate manipulations
were observed as another important cause associated
with VF attack. Traditionally, an impacted catheter was
regarded mainly as a manipulation-related cause of the
episode of VF during CA. In our data, most episodes
of manipulation-related VF were associated with superselective intubations. In addition, the injection-related VFs
(long or vigorous injection) were also common in the
episodes of manipulation-related VF. We considered that
these change were closely associated with the wide use of
small-sized catheters. When small-sized catheters are used,
manipulation-related VF often occurs during intracoronary
rapid flush of contrast medium on the condition of catheter
superselective intubation (often conus branch) or catheter
deep intubation.
In the past, the effect of contrast media had been extensively studied.3,5,9,16 The effect of intracoronary contrast
medium injections on the ECG have been described.3,9 In
our study, only two episodes of VF were associated with
the typical features of contrast-induced VF. We considered
that the contrast medium might not play a major role in the
genesis of VF on the condition of current techniques.
Among the 27 episodes of VF, there was one episode
associated with hypokalemia. Hypokalemia decreases the
threshold of VF and may be related to the mechanisms
of episodes of VF. The patients with electrolyte imbalance
should receive greater attention during CA.
It is not always so easy to analyze the specific mechanism and its relationship to each CA procedure. The causes
of VA occurrence are complicated; an episode of VF can
involve multiple causes. The assignment of cause might be
somewhat arbitrary. In addition, the absence of more information about the very large control group can also limit our
understanding of etiology of VF during CA. Despite these
limitations, our study, which lists some clinically detectable
causes of VF occurrence, is likely to provide useful
information for avoiding this troublesome complication.
The episodes of VF often involve multiple mechanisms.
A poor blood supply, contrast medium and hypokalemia can
make myocardium more susceptible to VF, and certain transient events, such as further acute ischemia and mechanical
stimulation, also play an important role in triggering a VF
attack. These indicated that we should take multiple factors
into comprehensive consideration to prevent VF occurrence.
In summary, the incidence of VF during CA is low on the
condition of current techniques; the severity of CAD may
be an important predictor of VF occurrence; the acute
level of ischemia and inappropriate manipulation might
be two of the main causes that are associated with the
episodes of VF during CA. The main procedural details for
reducing the possibility of VF include paying more attention
to severely affected CAD patients, a slow and careful
manipulation to reduce mechanical stimulation, avoidance
of catheter occlusion in large-sized catheters, avoidance of
deep intubation and superselective engagement in smallsized catheters, avoidance of a slow prolonged contrast
medium injection in patients with severe CAD, and a
rapid flash of contrast medium injection under conditions
of catheter occlusion, deep intubation and superselective
engagement.
References
1.
2.
3.
Bourassa MG, Noble J. Complication rate of coronary arteriography. A review of 5,250 cases studied by a percutaneous femoral
technique. Circulation. 1976;53:106–114.
Davis K, Kennedy JW, Kemp HG Jr, et al. Complications of
coronary arteriography from the collaborative study of coronary
artery surgery (CASS). Circulation. 1979;59:1105–1112.
Nishimura RA, Holmes DR, McFarland TM, Smith HC, Bove AA.
Ventricular arrhythmias during coronary angiography in patients
with angina pectoris or chest pain syndromes. Am J Cardiol. 1984;
53:1496–1499.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Johnson LW, Lozner EC, Johnson S, et al. Coronary arteriography
1984–1987: A report of the Registry of the Society for Cardiac
Angiography and Interventions. I. Results and complications.
Cathet Cardiovasc Diagn. 1989;17:5–10.
Brennan E, Mahrer PR, Aharonian VJ. Incidence and presumed
etiology of ventricular fibrillation during coronary angioplasty. Am
J Cardiol. 1991;67:769–770.
Missri J, Jeresaty RM. Ventricular fibrillation during coronary
angiography: reduced incidence with nonionic contrast media.
Cathet Cardiovasc Diagn. 1990;19:4–7.
Murdock DK, Johnson SA, Loeb HS, Scanlon PJ. Ventricular
fibrillation during coronary angiography: reduced incidence in
man with contrast media lacking calcium binding additives. Cathet
Cardiovasc Diagn. 1985;11(2):153–159.
Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines
for coronary angiography. A report of the American College of
Cardiology/American Heart Association Task Force on practice
guidelines (Committee on Coronary Angiography). Developed
in collaboration with the Society for Cardiac Angiography and
Interventions. J Am Coll Cardiol. 1999;33:1756–1824.
Morris TW. A review of coronary arteriography and contrast media
induced ventricular fibrillation. Acta Radiol. 1995;399:S100–S104.
Murdock DK, Lawless CE, Loeb HS, et al. Characterization of
ventricular fibrillation during coronary angiography. Am J Cardiol.
1985;55:249.
Horowitz LN, Spear JF, Josephson ME, Kastor JA, Moore EN. The
effects of coronary artery disease on the ventricular fibrillation
threshold in man. Circulation. 1979;60:792–797.
Murdock DK, Euler DE, Becker DM, et al. Ventricular fibrillation
during coronary angiography: an analysis of mechanisms. Am
Heart J. 1985;109:265–273.
Piao ZE, Murdock DK, Hwang MH, Raymond RM, Scanlon PJ.
Contrast media-induced ventricular fibrillation. A comparison of
Hypaque-76, Hexabrix, and Omnipaque. Invest Radiol. 1988;23:
466–670.
Huang JL, Ting CT, Chen YT, Chen SA. Mechanisms of ventricular
fibrillation during coronary angioplasty: increased incidence for the
small orifice caliber of the right coronary artery. Int J Cardiol. 2002;
82:221–228.
Addala S, Kahn JK, Moccia TF, et al. Outcome of ventricular
fibrillation developing during percutaneous coronary interventions
in 19,497 patients without cardiogenic shock. Am J Cardiol. 2005;
96:764–765.
Armstrong SJ, Murphy KP, Wilde P, Hartnell GG. Ventricular
fibrillation in coronary angiography: what is the role of contrast
medium? Eur Heart J. 1989;10:892–895.
Clin. Cardiol. 32, 5, 283–287 (2009)
J. Chen et al: Ventricular fibrillation during coronary angiography
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20394  2009 Wiley Periodicals, Inc.
287