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Imaging
risk in the contrast echocardiography group, these patients exhibited have reduced LV systolic function, there were no deaths in the
more significant comorbidities and illness severity than those group receiving contrast. One uncomplicated acute myocardial
undergoing non-contrast echocardiography.
21
infarction and one anaphylactoid reaction occurred in the contrast
agent group (p=0.51). Thus, while ultrasound contrast agents were
In a large multicenter, retrospective analysis conducted by the American more likely to be used in older hospitalized patients with depressed
Society of Echocardiography (ASE),
22
data on 78,383 contrast-enhanced LV systolic function, there was no increase in the rates of major
studies were reported (66,164 Definity and 12,219 Optison), including adverse events.
26
~10,000 critically ill patients hospitalized in intensive care units. In this
A second study evaluating the safety of ultrasound contrast agents
during stress echocardiography was reported by the Cleveland Clinic.
A series of 4,786 patients who underwent contrast-enhanced stress
Within the past year, several large-scale
echocardiograms (2,022 with dobutamine stress and 2,764 with
safety studies have been published that
exercise stress) were compared with a control group of 5,012 patients
matched for test year and type who did not receive an ultrasound
have objectively defined the safety profile
contrast agent. There was no difference in serious adverse event rate,
of ultrasound contrast agents in nearly
death within 24 hours, cardiac arrest, or sustained ventricular
tachycardia between the contrast and non-contrast groups.
27
200,000 patients.
Based on these new data (either published or in press in 2008), it
is reasonable to conclude that: serious adverse events consistent
study there were only eight serious adverse events (0.01%), four of which with anaphylactoid reactions occur in ~1:10,000 patient doses;
were serious and secondary to an anaphylactoid reaction (0.006%); none there is no increased mortality in hospitalized patients undergoing
of these occurred in the critically ill. There were no deaths attributable to contrast echocardiography compared with patients undergoing
ultrasound contrast agent use. These data were consistent with the very echocardiography without an ultrasound contrast agent, despite the fact
low serious adverse event rate in the Hennepin County database.
20
that patients receiving an ultrasound contrast agent exhibit more
comorbidities and higher acuity of illness; and contrast administration is
Main et al. utilized the Premier Perspective Database, the nation’s largest safe in stress echocardiography.
inpatient drug utilization database,
23
to analyze mortality in 4,300,966
patients who underwent inpatient echocardiography with 58,254 contrast- Subsequently, through FDA review of additional information received
enhanced studies.
24
Short-term mortality rates (death on the day of or day after October 2007, and in accordance with the findings of an FDA
following echocardiography) were similar in patients undergoing Cardio-Renal and Safety Advisory Committee meeting on June 24,
echocardiography with or without the use of an ultrasound contrast agent 2008, the FDA determined that, in some patients, the benefits from
(1.06 versus 1.08%; p=0.613). Multivariable logistic regression analysis the diagnostic information that could be obtained through the
(correcting for case mix and clinical co-variates) revealed that patients use of Definity or Optison may outweigh the risks for serious
receiving Definity were 24% less likely to die acutely compared with cardiopulmonary reactions, even among those patients at particularly
patients undergoing unenhanced echocardiography.
24
high risk for these reactions.
28,29
Although a ‘Boxed Warning’
continues to highlight the potential for “serious cardiopulmonary
A third, retrospective, multicenter study performed at Saint Louis
University, the University of Nebraska, and the Mayo Clinic (data acquired
between 1999 and 2007) evaluated a total of 42,408 consecutive patients
Seven recently published studies have
who received an ultrasound contrast agent. In 18,749 patients who
shown that there is no increased mortality
underwent stress echocardiography with contrast, there were no short-
term (30-minute) adverse events attributable to contrast, and 30-day
in patients undergoing contrast
myocardial infarction and mortality rates were similar in patients receiving
echocardiography compared with
a contrast agent compared with a control group. In 23,659 patients who
underwent resting contrast studies with short-term follow-up there were
patients undergoing echocardiography
no contrast-related serious adverse events at 30 minutes and no
without an ultrasound contrast agent.
difference in myocardial infarction or mortality rates at 24 hours compared
with a control group who did not receive a contrast agent.
25
complications,” all of the disease state contraindications issued in
Shaikh reported on 5,069 patients who underwent the stress October 2007 have been revised to ‘warnings,’ and the post-contrast
echocardiography procedure; an ultrasound contrast agent was 30-minute monitoring period now applies only to patients with
administered to 2,914 of these patients. A higher proportion of pulmonary hypertension and unstable cardiopulmonary conditions.
both inpatients and patients undergoing dobutamine stress had The FDA also recently announced that both manufacturers
contrast-enhanced studies. Despite the fact that patients receiving an (Lantheus Medical Imaging and GE Healthcare) have agreed to
ultrasound contrast agent tended to be older and were more likely to conduct two studies designed to further evaluate the safety of
18 US CARDIOLOGY
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