Journal of the American College of Cardiology
© 2004 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 43, No. 10, 2004
ISSN 0735-1097/04/$30.00
doi:10.1016/j.jacc.2003.09.072
Beta-Blockers in Myocardial Infarction
Sustained Ventricular Tachycardia or
Fibrillation in the Cardiac Catheterization
Laboratory Among Patients Receiving
Primary Percutaneous Coronary Intervention
Incidence, Predictors, and Outcomes
Rajendra H. Mehta, MD, MS,* Kishore J. Harjai, MD,† Lorelei Grines, PHD,† Gregg W. Stone, MD,‡
Judy Boura, MS,† David Cox, MD,§ William O’Neill, MD,† Cindy L. Grines, MD,† on behalf of the
Primary Angioplasty in Myocardial Infarction (PAMI) Investigators
Ann Arbor and Royal Oak, Michigan; New York, New York; and Charlotte, North Carolina
We sought to evaluate the incidence, predictors, and outcomes of ventricular tachycardia
and/or ventricular fibrillation (VT/VF) in the cardiac catheterization laboratory among
patients undergoing primary percutaneous coronary intervention (PCI).
BACKGROUND Although VT/VF has been known to occur during primary PCI, the current data do not
identify patients at risk for these arrhythmias or the outcomes of such patients.
METHODS
We evaluated 3,065 patients enrolled in the Primary Angioplasty in Myocardial Infarction
(PAMI) trials, who underwent primary PCI to evaluate the associations of VT/VF and the
influence of these arrhythmias on in-hospital and one-year outcomes.
RESULTS
In patients undergoing primary PCI, VT/VF occurred in 133 (4.3%). Multivariate analysis
identified the following as independent correlates of VT/VF: smoking (odds ratio [OR] 1.95,
95% confidence interval [CI] 1.26 to 3.02), lack of preprocedural beta-blockers (OR 2.34,
95% CI 1.35 to 4.07), time from symptom onset to emergency room of ⱕ180 min (OR 2.63,
95% CI 1.42 to 4.89), initial Thrombolysis In Myocardial Infarction (TIMI) flow grade 0
(OR 2.06, 95% CI 1.23 to 3.47), and right coronary artery-related infarct (OR 1.93, 95% CI
1.25 to 2.99). Although patients with VT/VF had a higher incidence of bradyarrhythmias,
hypotension, cardiopulmonary resuscitation, and endotracheal intubation in the catheterization laboratory, their in-hospital and one-year adverse outcomes were similar to those of the
cohort without these arrhythmias.
CONCLUSIONS Our findings suggest that the incidence of VT/VF during primary PCI is low, indicating that
these arrhythmias do not influence PCI success or in-hospital or one-year outcomes. Our data
further help identify patients at risk of VT/VF during primary PCI and suggest that
pretreatment with beta-blockers should be strongly considered to reduce these
arrhythmias. (J Am Coll Cardiol 2004;43:1765–72) © 2004 by the American College of
Cardiology Foundation
OBJECTIVES
Many studies have investigated the clinical and angiographic correlates and the prognostic significance of sustained ventricular tachycardia and/or ventricular fibrillation
(VT/VF) after thrombolytic therapy in patients with STsegment elevation myocardial infarction (STEMI) (1– 6).
See page 1788
Some of these investigations have suggested that these
ventricular arrhythmias are associated with coronary reperfusion, although others have related them to suboptimal
From the *University of Michigan, Ann Arbor, Michigan; †William Beaumont
Hospital, Royal Oak, Michigan; ‡Lenox Hill Hospital, New York, New York; and
§Mid Carolina Cardiology, Charlotte, North Carolina.
Manuscript received June 17, 2003; revised manuscript received August 27, 2003,
accepted September 8, 2003.
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
reperfusion (1– 6). The occurrence of VT/VF after thrombolysis has been shown to be associated with an increased
risk of in-hospital and one-year adverse events (6).
However, much less is known about the incidence, risk
factors, and prognosis of sustained VT/VF occurring in the
cardiac catheterization laboratory in patients with STEMI
undergoing primary percutaneous coronary intervention
(PCI). It is unclear how the rapid reperfusion achieved with
primary PCI (with an associated rapid change in the
metabolic cellular milieu, resulting in regional electrophysiologic instability), on the one hand, and the more complete
reperfusion, on the other (7–10), influence the propensity
and outcomes of these arrhythmias after primary PCI. The
purpose of the current investigation was to examine the
incidence, predictors, and outcomes of VT/VF occurring in
the cardiac catheterization laboratory among patients undergoing primary PCI.
1766
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
Abbreviations and Acronyms
CI
⫽ confidence interval
ECG ⫽ electrocardiogram/electrocardiographic
OR
⫽ odds ratio
PAMI ⫽ Primary Angioplasty in Myocardial Infarction
trial
PCI
⫽ percutaneous coronary intervention
RCA
⫽ right coronary artery
STEMI ⫽ ST-segment elevation myocardial infarction
TIMI ⫽ Thrombolysis In Myocardial Infarction
VF
⫽ ventricular fibrillation
VT
⫽ ventricular tachycardia
METHODS
Patient population. We pooled the data on 3,065 patients
enrolled in the four Primary Angioplasty in Myocardial
Infarction (PAMI) studies (including two trials with their
concomitant registries) that collected prospective data on
complications occurring in the cardiac catheterization laboratory (7,11–15). The rationale, methodology, and results
of the individual PAMI studies have been previously published (7,11–15). Patients were included in these investigations if they were ⱖ18 years old with STEMI presenting
within 12 h of their symptom onset. Acute STEMI was
defined as ST-segment elevation of at least 1 mm in two or
more contiguous leads or presumed new left bundle branch
block on the presenting 12-lead electrocardiogram (ECG)
in the presence of chest pain and/or elevation of cardiac
enzymes. Patients were excluded from these trials if they
had contraindications to reperfusion, had received thrombolytic therapy for index STEMI, or had renal failure,
cardiogenic shock, or a life expectancy ⬍1 year; those with
child-bearing potential; or those with known contraindications to aspirin, heparin, or ticlopidine in later PAMI trials
(11,14,15). Furthermore, patients randomized to the
thrombolytic arm in PAMI-1 were also excluded from this
analysis (7). Informed consent was obtained from all patients by the study investigators at the respective
institutions.
Data collection and angiographic analyses. A research
coordinator at each site collected data prospectively on
prespecified data elements on a case-report form in all trials.
These data included baseline demographics, medical history
(as reported by the patients, their families, or their referring
physicians, or determined from their previous medical
records), medications, procedures, complications, and clinical events. Follow-up was obtained at one year by a
telephone interview or follow-up visit to the physician.
Completed case-report forms were sent to the coordinating
site at Beaumont Hospital, Royal Oak, Michigan, where the
data were entered into an Access data base. The cineangiograms obtained at the time of the index intervention were
analyzed at the core laboratory site, where coronary anatomy, Thrombolysis In Myocardial Infarction (TIMI) flow
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
grades, percent diameter stenosis, left ventricular ejection
fraction, and angiographic outcomes of the intervention
were assessed.
Definitions, group comparisons, and study end points.
We categorized the study patients into two groups: those
with and those without sustained VT/VF occurring in the
cardiac catheterization laboratory during primary PCI. Ventricular fibrillation was defined as irregular undulations of
varying contour and amplitude on the ECG, with absent
distinct QRS and T waves and hemodynamic compromise
requiring direct-current defibrillation (Fig. 1A). Sustained
VT was defined as a regular wide-complex tachycardia of
ventricular origin lasting ⱖ30 s and/or accompanied by
hemodynamic compromise requiring electrical cardioversion
or anti-arrhythmic therapy (Fig. 1B). Re-infarction was
defined as recurrent symptoms or development of new ECG
changes accompanied by new elevation of creatine kinase,
MB enzyme levels. Ischemia-driven target vessel revascularization was defined as PCI or coronary artery bypass graft
surgery of the index infarct-related artery prompted by
symptoms or objective evidence of ischemia. Sustained
hypotension was defined as systolic blood pressure ⬍80 mm
Hg that was unresponsive to intravenous fluids, requiring
vasopressors for ⬎1 h or an intra-aortic balloon pump. For
this study, we compared the baseline clinical characteristics,
patient demographic features, coronary angiographic findings, and in-hospital adverse events of the two comparison
groups. The principal outcomes of interest included differences in the in-hospital and one-year mortality rates and the
in-hospital and one-year incidence of major adverse cardiovascular events (defined as death, or re-infarction, or ischemic target vessel revascularization) between these two
groups.
Statistical analysis. Summary statistics are presented as
frequencies and percentages or as median values. Comparisons between the two study groups were made using the
two-tailed Wilcoxon rank-sum test for continuous variables
and the chi-square or Fisher exact test (when the expected
frequency count in a cell was ⬍5) for categorical variables, as
appropriate. In all cases, denominators reflect cases reported. Stepdown multivariate logistic regression was constructed to identify clinical predictors of sustained VT/VF,
using variables showing a marginal association with it on
univariate testing (p ⬍ 0.10). Only variables with a significant (p ⬍ 0.05) association with sustained VT/VF were
included in the final regression models. Adjusted odds ratios
(ORs) and accompanying 95% confidence intervals (CIs)
were computed to determine the effect of each variable on
the risk of VT/VF in the final model. Diagnostic routines
(the Hosmer-Lemeshow test for lack of fit and the likelihood ratio test) were used for the final model selection. The
c statistic was calculated to evaluate model discrimination.
The Cochran-Mantel-Haenszel test was used for the analysis of trend. The software SAS version 8.0 (SAS Institute,
Cary, North Carolina) was utilized for all analyses.
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
1767
Figure 1. Electrocardiographic tracings of ventricular fibrillation (A) and ventricular tachycardia (B) during primary percutaneous coronary intervention.
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
1768
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
Table 1. Baseline Characteristics of Study Patients
Mean age (yrs)
Age ⱖ70 yrs
Females
Onset of symptom to ER (min)
ER to balloon time (min)
Medical history
Previous angina
Previous myocardial infarction
Previous congestive heart failure
Diabetes
Hypertension
Previous stroke
Hyperlipidemia
Peripheral vascular disease
Current smoker
Previous PCI
Previous CABG
COPD
Presentation
Pulse (beats/min)
Pulse ⬎100 beats/min
Systolic blood pressure (mm Hg)
Systolic blood pressure ⬍100 mm Hg
Killip class ⬎I
Medications before PCI
Aspirin
Heparin
Ticlopidine
Beta-blockers
No VT/VF Group
(n ⴝ 2,932)
VT/VF Group
(n ⴝ 133)
p Value
61 ⫾ 12
718 (25%)
780 (27%)
164 ⫾ 175 (111)
143 ⫾ 161 (113)
58 ⫾ 12
25 (19%)
33 (25%)
116 ⫾ 89 (89)
145 ⫾ 119 (120)
0.057
0.13
0.64
0.014
0.27
451 (15%)
425 (14%)
55 (1.9%)
479 (16%)
1,349 (46%)
154 (5.3%)
1,018 (35%)
167 (5.7%)
1,207 (41%)
272 (9.3%)
125 (4.3%)
78 (2.7%)
21 (16%)
17 (13%)
4 (3%)
15 (11%)
55 (41%)
6 (4.5%)
52 (39%)
6 (4.5%)
72 (54%)
13 (9.8%)
3 (2.3%)
1 (0.8%)
0.76
0.56
0.32*
0.12
0.33
0.72
0.42
0.57
0.0024
0.84
0.29*
1.00*
87 ⫾ 20
512 ⫾ 19
114 ⫾ 25
675 ⫾ 26
322 ⫾ 11.2
86 ⫾ 21
26 ⫾ 23
107 ⫾ 22
46 ⫾ 40
15 ⫾ 11.7
0.95
0.38
0.0015
0.0011
0.84
2,425 (83%)
2,074 (71%)
1,066 (36%)
854 (29%)
102 (77%)
82 (62%)
29 (22%)
19 (14%)
0.036
0.044
0.26
0.0003
*Derived using the Fisher exact test. Data are presented as the mean ⫾ SD (median) value or number (%) of subjects.
CABG ⫽ coronary artery bypass grafting; COPD ⫽ chronic obstructive pulmonary disease; ER ⫽ emergency room; PCI ⫽
percutaneous coronary intervention; SD ⫽ standard deviation; VF ⫽ ventricular fibrillation; VT ⫽ ventricular tachycardia.
RESULTS
Clinical and angiographic characteristics of patients with
and without VT/VF (Tables 1 and 2). Of the 3,065
patients with STEMI undergoing primary PCI in the study,
133 (4.3%) had VT/VF during the procedure. The majority
of patients with VT/VF required cardioversion/defibrillation
(79%), whereas anti-arrhythmic drugs were used to restore
sinus rhythm in the remaining patients. Compared with the
cohort without VT/VF, those with these arrhythmias were
more likely to be current smokers, with a trend toward being
of younger age. Other patient demographics and medical
history were similar in the two groups. The time from
symptom onset to emergency room presentation was shorter
in the group with VT/VF, with no difference in the
door-to-balloon time. Systolic blood pressure on arrival was
lower in patients with VT/VF. Aspirin, heparin, and betablockers were given less frequently before arriving at the
cardiac catheterization laboratory in patients with VT/VF.
As a result, the first activated clotting time in the catheterization laboratory was significantly lower in these patients.
Important differences also existed in the angiographic
characteristics between the two groups. Patients with
VT/VF were more likely to have initial TIMI flow grade 0,
higher initial percent stenosis of the infarct-related artery,
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
and the right coronary artery (RCA) as their infarct artery.
The postprocedural final percent stenosis and non–flowlimiting infarct artery dissection were higher in patients
with VT/VF, with no difference between other postprocedural angiographic features, such as TIMI flow rates or the
presence of thrombus.
Complications in the catheterization laboratory, in the
hospital, and at one-year follow-up in patients with and
without VT/VF (Tables 2 and 3). Patients with VT/VF
had a significantly higher incidence of bradyarrhythmias,
hypotension, cardiopulmonary resuscitation, and the need
for endotracheal intubation in the catheterization laboratory. Despite this, neither the mortality in the catheterization laboratory nor the in-hospital or one-year adverse
outcomes differed between the two groups. The median
length of stay was a day longer in the VT/VF group.
Clinical factors related to VT/VF (Table 4). Stepdown
logistic regression analysis identified current smoking,
shorter time from symptom onset to emergency room
presentation, lack of beta-blocker therapy in the emergency
room, RCA-related STEMI, and lower TIMI flow grades
on admission as independent correlates of VT/VF. By
imputing the presence or absence of these risk variables for
VT/VF in a patient (yes ⫽ 1; no ⫽ 0) into the equation
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
1769
Table 2. Angiographic Data and Catheterization Laboratory Complications of Study Patients
Initial angiographic data
Infarct-related artery
LMCA
LAD
LCx
RCA
Bypass graft
Multivessel disease
TIMI flow grade
0
1
2
3
Percent stenosis
LVEF (%)
Medications, IABP, and stent use during procedure
Glycoprotein IIb/IIIa inhibitors
Thrombolytics
Stents
IABP
Initial activated clotting time (s)
Postprocedural angiographic data
TIMI flow grade
0
1
2
3
Percent stenosis
Thrombus
Final dissection
Catheterization laboratory complications
Bradyarrhythmias
Cardiopulmonary resuscitation
Endotracheal intubation
Hypotension
Death
No VT/VF Group
(n ⴝ 2,932)
VT/VF Group
(n ⴝ 133)
18 (0.6%)
1,111 (37.8%)
431 (14.7%)
1,199 (40.8%)
39 (1.3%)
1,414 (48.2%)
1 (0.8%)
38 (28.6%)
15 (11.3%)
77 (57.9%)
0
53 (40%)
1,754 (59.8%)
332 (11.3%)
419 (14.3%)
324 (11%)
97.4 ⫾ 7 (100)
49 ⫾ 12
105 (78.9%)
7 (5.3%)
12 (9%)
8 (6%)
98.7 ⫾ 4 (100)
50 ⫾ 12
62 (2.1%)
125 (4.3%)
894 (31%)
38 (1.3%)
234 ⫾ 159
5 (3.7%)
10 (7.5%)
35 (26.3%)
5 (3.7%)
167 ⫾ 182
39 (1.3%)
21 (0.7%)
137 (4.6%)
2,417 (82.4%)
16 ⫾ 18 (10)
247 (8.4%)
341 (11.6%)
0
0
6 (4.5%)
123 (92.5%)
18 ⫾ 15 (20)
18 (13.5%)
29 (21.8%)
0.22
0.024
0.24
0.018
281 (9.6%)
13 (0.4%)
20 (0.7%)
141 (4.8%)
3 (0.1%)
46 (34.6%)
8 (6%)
6 (4.5%)
21 (15.8%)
1 (0.7%)
⬍ 0.0001
⬍ 0.0001
⬍ 0.0018
⬍ 0.0001
0.19*
p Value
0.018
0.23
0.0002
0.068
0.0008
0.0007
0.51
0.40
0.28
0.30
0.16
⬍ 0.0001
*Derived using the Fischer exact test. Data are presented as the number (%) of subjects or mean ⫾ SD (median) value.
IABP ⫽ intra-aortic balloon pump; LAD ⫽ left anterior descending coronary artery; LCx ⫽ left circumflex artery; LMCA
⫽ left main coronary artery; LVEF ⫽ left ventricular ejection fraction; RCA ⫽ right coronary artery; TIMI ⫽ Thrombolysis
In Myocardial Infarction; VF ⫽ ventricular fibrillation; VT ⫽ ventricular tachycardia.
shown in the Appendix and solving this equation, an
estimate of the absolute risk of VT/VF in an individual
patient during primary PCI can be obtained. The frequency
of VT/VF increased as the time from symptom onset to
emergency room arrival decreased (Fig. 2). Also, the frequency of VT/VF increased as the number of risk predictors
increased: from none in patients with no risk factors to
12.6% in those with all five risk variables (Fig. 3).
DISCUSSION
Findings of the present study. Our study suggests that
VT/VF occurs infrequently in the cardiac catheterization
laboratory in patients undergoing primary PCI and identifies clinical and angiographic factors associated with this
adverse event. Importantly, it shows that although the
occurrence of VT/VF during primary angioplasty is associated with a greater length of stay, it does not have an impact
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
on the procedural success or risk of adverse in-hospital and
long-term outcomes.
Thus, our study findings are in contrast to those of large
trials evaluating VT/VF in patients with STEMI receiving
thrombolytic therapy, which have reported a higher incidence of up to 20% and a greater risk of adverse short- and
long-term outcomes with this arrhythmia (1– 6). Previous
studies have shown that the size of myocardial infarction not
only correlates with an increased incidence of VT/VF, but is
also an important predictor of mortality in patients with
STEMI (5,6,16 –18). Compared with thrombolysis, primary PCI is associated with greater myocardial salvage, a
smaller infarct size, and a better ejection fraction (7–10). In
patients treated with thrombolytic therapy, failed reperfusion is more common in the cohort with VT/VF than in
those without these arrhythmias (6). Primary PCI is associated with not only more complete reperfusion (and fewer
patients with TIMI flow grade 0), but also rapid reperfusion
1770
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
Table 3. In-Hospital Complications and Long-Term Outcomes
In-hospital events
Bradyarrhythmias
Pulmonary edema
Sustained hypotension
Cardiopulmonary resuscitation
Need for dialysis
CABG
Gastrointestinal bleeding
Median length of stay (days)
In-hospital outcomes
Re-infarction
Ischemic TVR
Death
MACE
Disabling stroke
One-year outcomes
Re-infarction
Ischemic TVR
Death
MACE
Disabling stroke
No VT/VF
Group
(n ⴝ 2,932)
VT/VF
Group
(n ⴝ 133)
p
Value
71 (2.4%)
80 (2.7%)
106 (3.6%)
19 (0.6%)
13 (0.4%)
245 (8.3%)
63 (2.1%)
5
7 (5.3%)
7 (5.3%)
9 (6.7%)
0
0
7 (5.2%)
4 (3%)
6
0.080
0.23
0.23
1.00*
1.00*
0.23
0.34*
0.019
33 (1.1%)
87 (2.9%)
84 (2.9%)
182 (6.2%)
6 (0.2%)
1 (0.8%)
7 (5.3%)
4 (3.0%)
11 (8.3%)
0
1.00*
0.12
0.79
0.34
1.00*
97 (3.3%)
312 (10.6%)
163 (5.5%)
528 (18%)
12 (0.4%)
3 (2.2%)
18 (13.5%)
6 (4.5%)
24 (18%)
0
1.00*
0.09
0.72
0.75
1.00*
*Derived using the Fisher exact test. Data are presented as the number (%) of subjects.
CABG ⫽ coronary artery bypass graft; MACE ⫽ major adverse cardiovascular
events (re-infarction, or ischemia driven TVR or death); TVR ⫽ target vessel
revascularization; other abbreviations as in Table 1.
(7–10). Thus, it is not surprising that unlike previous reports
of VT/VF occurring after thrombolysis (1– 6), the incidence
of ventricular arrhythmias occurring with primary PCI is
low and does not increase the risk of in-hospital and
long-term mortality.
Clinical and angiographic factors associated with the risk
of VT/VF in patients undergoing primary PCI. Our
study identified several clinical and angiographic variables as
independent predictors of VT/VF in the cardiac catheterization laboratory during primary PCI. These included a
history of current smoking, time from symptom onset to
emergency room arrival, lack of beta-blocker therapy in the
emergency room, RCA-related infarct, and initial TIMI
flow grade 0 of the infarct-related artery.
Nicotine stimulates catecholamine release and increases
the heart rate and blood pressure (19). An increased level of
carbon monoxide in smokers further reduces myocardial
Figure 2. Time from symptom onset to emergency room (ER) arrival and
frequency of ventricular tachycardia/ventricular fibrillation (VT/VF). The
Cochran-Mantel-Haenszel statistic ⫽ 9.2, df 1, p ⬍ 0.0024 for trend.
oxygen delivery (20). In addition, smoking has been shown
to injure endothelial cells (21) and reduce prostacyclin
production (22). These effects induce coronary vasospasm of
both epicardial and myocardial resistance vessels, particularly in diseased coronary arteries. Smokers are also more
likely to be younger—a population that is likely to have
greater catecholamine surge with stress, as compared with
elderly patients. Thus, both increased catecholamine levels
and a greater propensity for vasospasm may make smokers
particularly susceptible to VT/VF after primary PCI, which
leads to rapid electrophysiologic instability of the myocardium.
The speed of reperfusion has been shown to increase the
rate of reperfusion arrhythmias. In animal studies, brief
periods (5 to 15 min) of coronary artery occlusion followed
by reperfusion are often associated, at the time of reflow,
with dramatic increase in ventricular arrhythmias (23,24). If
the duration of ischemia is extended to 1 to 3 h, followed by
reperfusion, ventricular arrhythmias may still be present
during the phase of ischemia, but reperfusion is not associated with as dramatic an increase in VT/VF (25). Clinical
data support these preliminary animal observations. A
pooled analysis of intracoronary thrombolysis trials suggests
that VT/VF was more likely to occur when the interval
between the onset of infarction and thrombolytic therapy
was short (25). Similarly, in patients receiving intravenous
Table 4. Adjusted Odds Ratios of Clinical Variables Associated
With the Risk of Ventricular Tachycardia or Fibrillation During
Primary Percutaneous Coronary Intervention
Outcome
Current smoker
No beta-blocker in the ER
RCA as infarct artery
Time from symptom onset
to ER ⱕ180 min
Initial TIMI flow grade 0
Odds
Ratio
95%
Confidence
Interval
p Value
1.95
2.34
1.93
2.63
1.26–3.02
1.35–4.07
1.25–2.99
1.42–4.89
0.0027
0.0026
0.0033
0.0022
2.06
1.23–3.47
0.0062
Model c statistic ⫽ 0.72; Hosmer-Lemeshow chi-square ⫽ 6.03; df 8; p ⫽ 0.64.
ER ⫽ emergency room. Other abbreviations as in Tables 1 and 2.
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
Figure 3. Increasing number of risk factors for ventricular tachycardia/
ventricular fibrillation (VT/VF) (as shown in Table 4) and the incidence of
these arrhythmias. The Cochran-Mantel-Haenszel statistic ⫽ 50.7, df 1, p
⬍ 0.0001 for trend.
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
thrombolysis, VT/VF was more likely to occur when the
time to treatment was shorter (6,26). The inverse relationship of the time from symptom onset to emergency room
and the risk of VT/VF in our study is thus consistent with
these previous observations.
The use of beta-blockers in patients with STEMI in the
pre-thrombolysis era has been shown to be associated with
a reduction in early mortality, cardiac rupture, and ventricular arrhythmias (27,28). This beneficial effect of betablockers in reducing the incidence of VT/VF was also
shown in patients receiving thrombolytic therapy (6). Our
data are consistent with these earlier observations and
extend the paradigm of the benefits of beta-blockers to
patients receiving primary PCI. Thus, previous studies and
our investigation suggest that beta-blockers are not only
useful in preventing ischemia-mediated VT/VF (in nonreperfused patients), but also in reducing the incidence of
these arrhythmias. These findings argue in favor of routine
use of early beta-blocker therapy for all patients with
STEMI, including those receiving primary PCI, to reduce
the incidence of VT/VF, as well as to improve outcomes.
Similar to the finding in our investigation, the risk of
VT/VF has been shown to increase in patients with STEMI
related to the RCA, who are receiving thrombolytic therapy
(5,6,18), even in those undergoing rescue angioplasty (29).
Several potential mechanisms may be implicated in this
increased risk of VT/VF during reperfusion of an infarct
related to the RCA. Sudden reperfusion of the RCA
increases vagal tone through the Bezold-Jarisch reflex,
which, in turn, results in a marked compensatory increase in
sympathetic tone (29). Further, RCA-related infarctions are
more common among younger patients and smokers (30),
individuals who are more likely to have markedly heightened sympathetic tone, particularly after stress such as
STEMI.
Finally, animal studies have demonstrated that the severity of ischemic injury governs the extent of reperfusion
injury (23,24). The greater the degree of myocardial hypoperfusion, the greater is the rate of formation of free radicals
with reperfusion, and hence the greater chance of reperfusion arrhythmias (31). An increased heart rate worsens the
severity of ischemic injury, augmenting the incidence of
reperfusion arrhythmias (32). Conversely, agents that reduce the heart rate (beta-blockers) decrease reperfusion
arrhythmias (33). Our investigation concurs with these
animal experiments in that VT/VF was more common in
patients undergoing primary PCI who had more severe
ischemia at the onset (those with TIMI flow grade 0),
compared with those with a lesser severity of ischemia
(TIMI flow grade ⱖ1). Also, patients with TIMI flow
grade 0 are more likely to have true reperfusion arrhythmias,
as opposed to those with partial flow (TIMI flow grade ⱖ1).
Conclusions. Our study suggests that in patients undergoing primary PCI, VT/VF occurs infrequently in the cardiac
catheterization laboratory and does not influence PCI success or in-hospital or one-year outcomes when treated
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
1771
promptly. Our data further help identify clinical and angiographic variables associated with an increased risk of these
arrhythmias during primary PCI and suggest that prophylactic treatment with beta-blockers may be the best strategy
to prevent ventricular arrhythmias in patients undergoing
primary PCI.
Reprint requests and correspondence: Dr. Cindy L. Grines,
William Beaumont Hospital, 3601 West 13 Mile Road, Royal
Oak, Michigan 48073. E-mail: cgrines@beaumont.edu.
REFERENCES
1. Zehender M, Utzolino S, Furtwangler A, et al. Time course and
interrelation of reperfusion-induced ST changes and arrhythmias in
acute myocardial infarction. Am J Cardiol 1991;68:1138 –42.
2. Gressin V, Louvard Y, Pezzano M, Lardouz H. Holter recording of
ventricular arrhythmias during intravenous thrombolysis for acute
myocardial infarction. Am J Cardiol 1992;69:152–9.
3. Six AJ, Louwerenburg JH, Kingma JH, et al. Predictive value of
ventricular arrhythmias for patency of infarct-related coronary artery
after thrombolytic therapy. Br Heart J 1991;66:143–6.
4. Buckingham TA, Devine JE, Redd RM, Kennedy HL. Reperfusion
arrhythmias during coronary reperfusion therapy in man: clinical and
angiographic correlations. Chest 1986;90:346 –51.
5. Berger PB, Ruocco NA, Ryan TJ, et al. Incidence and significance of
ventricular tachycardia and fibrillation in the absence of hypotension or
heart failure in acute myocardial infarction treated with recombinant
tissue-type plasminogen activator: results from the Thrombolysis in
Myocardial Infarction (TIMI) phase II trial. J Am Coll Cardiol
1993;22:1773–9.
6. Newby KH, Thompson T, Stebbins A, et al. Sustained ventricular
arrhythmias in patients receiving thrombolytic therapy: incidence and
outcomes. Circulation 1998;98:2567–73.
7. Grines CL, Browne KF, Marco J, et al., the Primary Angioplasty in
Myocardial Infarction Study Group. A comparison of immediate
angioplasty with thrombolytic therapy for acute myocardial infarction.
N Engl J Med 1993;328:673–9.
8. Zijlstra F, de Boer MJ, Hoorntje JC, et al. A comparison of immediate
coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680 –4.
9. Gibbons RJ, Holmes DR, Reeder GS, et al., the Mayo Coronary Care
Unit in Catheterization Laboratory Groups. Immediate angioplasty
compared with the administration of a thrombolytic agent followed by
conservative treatment for myocardial infarction. N Engl J Med
1993;328:685–91.
10. The Global Use of Strategies to Open Occluded Coronary Arteries in
Acute Coronary Syndromes (GUSTO-IIb) Angioplasty Substudy
Investigators. A clinical trial comparing primary coronary angioplasty
with tissue plasminogen activator for acute myocardial infarction.
N Engl J Med 1997;336:1621–8.
11. Grines CL, Cox DA, Stone GW, et al., the Stent Primary Angioplasty
in Myocardial Infarction Study Group. Coronary angioplasty with or
without stent implantation for acute myocardial infarction. N Engl
J Med 1999;341:1949 –56.
12. Stone GW, Marsalese D, Brodie BR, et al., the Second Primary
Angioplasty in Myocardial Infarction (PAMI-II) Investigators. A
prospective, randomized evaluation of prophylactic intraaortic balloon
counterpulsation in high risk patients with acute myocardial infarction
treated with primary angioplasty. J Am Coll Cardiol 1997;29:1459 –
67.
13. Grines CL, Marsalese D, Brodie B, et al., for the PAMI-II Investigators. Safety and cost effectiveness of early discharge after primary
angioplasty in low risk patients with acute myocardial infarction. J Am
Coll Cardiol 1998;31:967–72.
14. Stone GW, Brodie BR, Griffin JJ, et al. Prospective, multicenter study
of the safety and feasibility of primary stenting in acute myocardial
infarction: in-hospital and 30-day results of PAMI Stent Pilot trial.
J Am Coll Cardiol 1998;31:23–30.
15. Stone GW, Brodie BR, Griffin JJ, et al. Clinical and angiographic
follow-up after primary stenting in acute myocardial infarction: the
1772
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
Mehta et al.
Ventricular Arrhythmias Treated With Primary PCI
Primary Angioplasty in Myocardial Infarction (PAMI) Stent Pilot
trial. Circulation 1999;99:1548 –54.
Tofler GH, Stone PH, Muller JE, et al. Prognosis after cardiac arrest
due to ventricular tachycardia or ventricular fibrillation associated with
acute myocardial infarction (the MILIS study). Am J Cardiol 1987;
60:755–61.
Volpi A, Maggioni A, Franzosi MG, et al. In-hospital prognosis of
patients with acute myocardial infarction complicated by primary
ventricular fibrillation. N Engl J Med 1987;317:257–61.
Maggioni AP, Zuanetti G, Franzosi MG, et al., on behalf of the
GISSI-2 Investigators. Prevalence and prognostic significance of
ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era: GISSI-2 results. Circulation 1993;87:312–22.
Cryer PE, Haymond MW, Santiago JV, Shah SD. Norepinephrine
and epinephrine release and adrenergic mediation of smokingassociated hemodynamic and metabolic events. N Engl J Med 1976;
295:573–7.
Wald N, Howard S, Smith PG, Kjeidsen K. Association between
atherosclerotic diseases and carboxyhemoglobin levels in tobacco
smokers. BMJ 1973;1:761–5.
Zimmerman M, McGeachie J. The effect of nicotine on aortic
endothelium: a quantitative ultrastructural study. Atherosclerosis
1987;63:33–41.
Reinders JH, Brinkman HJ, van Mourik JA, de Groot PG. Cigarette
smoke impairs endothelial cell prostacyclin production. Atherosclerosis 1986;6:15–23.
Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol 1984;16:497–518.
Hale SL, Lange R, Alker KJ, Kloner RA. Correlates of reperfusion
ventricular fibrillation in dogs. Am J Cardiol 1984;53:1397–400.
Hagar JM, Kloner RA. Reperfusion arrhythmias: experimental and
clinical aspects. The Age of Reperfusion 1990;2:1–5.
Solomon SD, Ridker PM, Antman EM. Ventricular arrhythmias in
trials of thrombolytic therapy for acute myocardial infarction: a
meta-analysis. Circulation 1993;88:2575–81.
The MIAMI Trial Research Group. Metoprolol In Acute Myocardial
Infarction (MIAMI): a randomized placebo-controlled international
trial. Eur Heart J 1985;6:199 –226.
The First International Study of Infarct Survival (ISIS-1) Collaborative Group. Mechanisms for the early mortality reduction produced by
Downloaded From: https://content.onlinejacc.org/ on 09/30/2016
JACC Vol. 43, No. 10, 2004
May 19, 2004:1765–72
29.
30.
31.
32.
33.
beta-blockade started early in myocardial infarction: ISIS-1. Lancet
1988;1:921–3.
Gacioch GM, Topol EJ. Sudden paradoxic clinical deterioration
during angioplasty of the occluded right coronary artery in acute
myocardial infarction. J Am Coll Cardiol 1989;14:1202–9.
Barbash GI, Reiner J, White HD, et al. Evaluation of paradoxic
beneficial effects of smoking in patients receiving thrombolytic therapy
for acute myocardial infarction: mechanism of the ‘smokers paradox’
from the GUSTO-I trial, with angiographic insights. J Am Coll
Cardiol 1995;26:1222–9.
Bolli R, Patel BS, Jeroudi MO, et al. Demonstration of free radical
generation in ‘stunned’ myocardium of intact dogs with the use of spin
trap alpha-phenyl N-tert-butyl nitrone. J Clin Invest 1988;82:476 –85.
Lederman SN, Wenger TL, Harrell FE, et al. Effects of different
paced heart rates on canine coronary occlusion and reperfusion
arrhythmias. Am Heart J 1987;113:1365–9.
Miyazawa K, Fukuyama H, Komatsu E, et al. Effects of propranolol
on myocardial damage resulting from coronary artery occlusion followed by reperfusion. Am Heart J 1986;111:519 –24.
APPENDIX
Calculation of predicted risk using patient data and
logistic regression coefficients. To calculate the odds of
risk of VT/VF during the procedure for an individual
undergoing primary PCI: exp ([⫺5.7521] ⫹ [0.6690 ⫻
current smoker] ⫹ [⫺0.8504 ⫻ beta-blocker therapy in
emergency room] ⫹ [0.6576 ⫻ RCA as infarct-related
artery] ⫹ [0.9676 ⫻ time from symptom onset to emergency room arrival ⱕ180 min] ⫹ [0.7243 ⫻ initial TIMI
flow grade 0]). In the equation, the risk variables in a patient
undergoing primary PCI are entered as: present ⫽ 1;
absent ⫽ 0. The predicted risk (probability) of VT/VF
during primary angioplasty is calculated as: odds/(1 ⫹
odds).