Safety and Efficacy of Commercially Available Ultrasound Contrast Agents in the Clinical Setting

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Safety and Efficacy of Commercially Available
Ultrasound Contrast Agents in the Clinical Setting

• Melda S. Dolan, MD Simil Gala, MD Saritha
  Dodla, MD Feng Xie, MD David Cloutier, MD
• Thomas Porter, MD Arthur J. Labovitz, MD.

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ACC Disclosure

• Melda S. Dolan, MD Nothing to disclose
• Simil Gala, MD Nothing to disclose
• Saritha Dodla, MD Nothing to disclose
• Feng Xie, MD Grant
• David Cloutier, MD Nothing to disclose
• Thomas Porter, MD Grant, Consultant
• Arthur J. Labovitz,MD Nothing to disclose

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Background
Up To 20-30 of Echoes Technically Difficult
Large Body Habitus
Chest Wall Deformities
Severe Chronic Lung Disease
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Non Contrast Contrast
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Background
Before 1997
1997
2007
Phase III Studies 1700 Patients No Safety
Concerns
UCA FDA Approval
Black Box Warning On Optison Definity
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Over 2 million Doses Administered
11 Deaths Overall
4 Deaths Within 30 min.
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Black box WarningNew Contraindications

• R?L, bi-directional, or transient R?L cardiac
  shunts
• Clinically unstable or recent worsening
  congestive heart failure
• Acute Coronary Syndrome
• Serious ventricular arrhythmias or at high risk
  for arrhythmias due to QT prolongation
• Respiratory failure
• Severe emphysema, pulmonary emboli or other
  conditions that compromise pulmonary arterial
  vasculature

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Aim of Study

• Define overall incidence of events after contrast
  administration in the short and longer term.
• Outline risk versus benefits profile of contrast
  use during echocardiograpic exams transthoracic
  and stress.

Risks
Benefits
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Patient Characteristics
Retrospectively Analyzed 23659 Consecutive
Patients with resting Echo From Saint Louis
University and University of Nebraska
Short Term Follow-Up
24 Hrs.
30 Min.
Non-Fatal Myocardial Infarctions Death From All
Causes
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Patient Characteristics
N23659
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Results
Retrospectively Analyzed 23659 Consecutive
Patients CONTRAST Resting Echo From Saint Louis
University and University of Nebraska
Short Term Follow-Up
30 Min.
24 Hrs.
No Events
3 Non-Fatal MI and 1 Death
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Results Contrast Echo Short Term Follow up
N 23659
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Results
Retrospectively Analyzed 5900 Consecutive
Patients NON CONTRAST Resting Echo From Saint
Louis University and University of Nebraska
Short Term Follow-Up
30 Min.
24 Hrs.
No Events
7 Non-Fatal MI and 1 Death
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Baseline Demographics
Resting Echo Quality Contrast NonDiagnostic N23659 No Contrast Diagnostic N5900 P
Male 66.4 60.2 NS
Hypertension 59 54.3 NS
DM 38 32 NS
Hyperlipidemia 54 51 NS
Smoking 49 41 NS
Previous MI 16 12 NS
Previous CABG 9 7 NS
Previous PTCA 18 14 NS
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Results NonContrast Echo Short Term Follow up
N 5900
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DSECONTRAST vs. NON CONTRAST
4011 Patients Who Received Contrast for
Suboptimal Images
1923 Matched Patients With Optimal Image
Quality Without Contrast
Versus
Angiography
Specificity
Sensitivity
Angiography
Accuracy
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Baseline Demographics
DSE Quality Contrast NonDiagnostic No Contrast Diagnostic P
Male 61.4 58.2 NS
Hypertension 56 52 NS
DM 32 29 NS
Hyperlipidemia 48 54 NS
Smoking 39 36 NS
Previous MI 14 10 NS
Previous CABG 10 7 NS
Previous PTCA 16 12 NS
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DSE Data
DSE Image Quality Contrast NonDiagnostic No Contrast Diagnostic P
Normal 61.7 63.8 NS
Fixed 10.8 9.8 NS
Ischemia 13.8 12.1 NS
Fixed Isch 14.1 12.8 NS
Target HR 84.2 83.7 NS
Rest EF 56.9 10.2 58.28.7 NS
Chest Pain 12.6 13.7 NS
Dyspnea 6.8 7.6 NS
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Angiographic Data
DSE Image Quality Contrast NonDiagnostic No Contrast Diagnostic P
Stenosis Severity 74 10 7014 NS
Single Vessel 58 54 NS
2 Vessel 21 25 NS
3 Vessel 12 11 NS
LAD 49 54 NS
CX 24 19 NS
RCA 22 20 NS
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Results
DSE Image Quality Contrast NonDiagnostic No Contrast Diagnostic P
Sensitivity 81 73 NS
Single Vessel 74 68 NS
Multivessel 85 83 NS
Accuracy 82 76 NS
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Myocardial Perfusion
6075 Patients Analyzed to Determine Added
Benefit Of Myocardial Perfusion Imaging With
Respect to Long Term Follow-Up
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Results
Long Term Follow-Up 6075 Patients 2-92 Months
237 Non-Fatal MI 273 Deaths
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Results
6075 Patients Analyzed to Determine Added
Benefit Of Myocardial Perfusion Imaging With
Respect to Long Term Follow-Up
4251 Normal Studies
Adverse Events N133(3.7)
Adverse Events N377(20.6)
1824 Abnormal Studies
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Results
510 EVENTS
133 Normal WM Normal MP
291 Abnormal WM Abnormal MP
86 Normal WM Abnorm MP
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5 Year Event Free Survival



plt0.05
Stress Contrast Myocardial Perfusion
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Univariate Predictors Multivar. Predictors
Variables RR(95CI) p RR(95 p
Agegt70 1.5(1.0-2.4) 0.05 NS
Hyperlipid 0.6(0.5-1.0) 0.31 NS
Hyperten. 0.8(0.5-1.0) 0.12 NS
DM 1.2(0.9-1.6) 0.92 NS
Pre CABG 2.2(1.3-3.8) 0.001 NS
Pre MI 2.1(1.2-3..4) 0.001 0.6(0.4-0.9) 0.01
EFlt50 1.6 (0.7-4.1) 0.001 1.4(1.0-1.8) 0.01
Abn WM 3.9(2.9-5.7) 0.001 NS
Abn MP 5.0(3.4-8.7) 0.001 2.4(1.0-5.9) 0.001
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Summary

• The risk of both short-term and long-term events,
  defined as non-fatal myocardial infarction and
  death, following contrast administration during
  resting echo is very low.
• Not different from non-contrast studies.

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Summary

1. In patients undergoing DSE, the risk of an
   adverse event in a patient that received contrast
   was comparable to patients that did not receive
   contrast

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Summary

• The benefits of contrast use in patients with
  suboptimal images are significant and outweigh
  the possible risks.
• Making suboptimal studies equivalant to optimal
  studies
• Preventing additional costly tests

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Summary

• Myocardial perfusion assessment with contrast
  echo
• Adds significant prognostic value

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Conclusion

• In light of these findings regarding safety and
  benefits, the FDA should reconsider the black box
  warning placed on contrast agents used during
  echocardiography.

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