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Where Contrast Administration Makes a Difference

Contrast 2017State of the Art

Linda D. Gillam, MD, MPH, FASE

Chair, Cardiovascular Medicine

Medical Director, CV Service Line

Morristown Medical Center/Atlantic Health System

Morristown, NJ

Professor of Medicine

Thomas Jefferson University

No disclosures

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Contemporary Ultrasound Contrast Agents

Stabilized gas microspheres sized to pass through the smallest capillaries

Burns. In: Rumack et al, eds. Diagnostic Ultrasound. Vol 1. 2nd ed. St. Louis: Mosby; 1998:57.

RBC: 6-8 m

Microsphere: 2-5 m

Currently available agents

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POWER

Interaction of Ultrasoundand Microbubbles

Linearresonance

Nonlinearresonance

Transientscattering

POWER POWER

Fundamentalenhancement

Bubble disruption

Harmonic enhancement

Burns. In Rumack et al, eds. Diagnostic Ultrasound. Vol. 1. 2nd ed. St. Louis: Mosby; 1998:57.

Principles of Harmonic Imaging

2.5 MHz

2.5 MHz• Tissue and blood reflect

at the fundamental frequency

• Microbubbles reflect at both the fundamental and the harmonic frequencies

2.5 MHz2.5 MHz + 5 MHz

Burns. In Rumack et al, eds. Diagnostic Ultrasound. Vol. 1. 2nd ed. St. Louis: Mosby; 1998:57.

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Fundamental and Harmonic Contrast Imaging

Schrope and Newhouse. Ultrasound Med Biol. 1993;19:567.Shapiro et al. Am J Roentgenol. 1998; 171:1203-1206.

Contrast

Tissue

It’s all about signal to noise!

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Machine Settings

• For most applications– Aim to maximize non-linear harmonic reflecting responses

(MI 0.1-0.4)• Improves signal to noise vs tissue

• Equipment– Optimized settings (presets)

• Contrast agent specific

• Transducer specific

• For perfusion applications– Controlled bubble destruction

– Works best with equipment specifically equipped to do perfusion imaging

Technical capability and Operational excellence

Diagnostic capacity

Impact on diagnostic and prognostic thinking

Impact on therapeutic strategy

Cost effectiveness

Outcomes

Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies. CMAJ 1986; 134:587-594.

Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making 1991; 11:88-94

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LVO/EBD, Doppler enhancement

LVEF, Quantitation of gradients

Prognosis/dx related to LV function and gradients

Rx: Devices/ intervention for AS

Cost effectiveness

Outcomes

Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies. CMAJ 1986; 134:587-594.

Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making 1991; 11:88-94

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Case Examples

Myocardial Contrast Perfusion

Thanks to Tom Porter, MD

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Post PCI

Thanks to Tom Porter

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Safety Concerns

Class Box Warning

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Old contraindications

Current for all agents

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Lumason®

and pediatric

CARPA

Complement Activation Related Pseudo-Allergy

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CARPA Signs and Symptoms• Angioedema

• Bronchospasm

• Cyanosis

• Hypotension

• Low back pain

• Pruritis

• Urticaria

• Tingling sensation

• Hypoxemia

• Sneezing

Acute Hypersensitivity Reactions

IgE mediated type I• Reaction after

repeated exposure

• Reaction is stronger upon repeated exposure

• Reaction does not cease without treatment

CARPA• No prior exposure

necessary

• Reaction is milder or absent upon repeated exposures

• Spontaneous resolution

Szebeni J. Toxicology 2005:216:106-121

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Note that prior “allergic” reaction is contra-indication to

use of same/similar agent

Event Rates for Commonly Performed Cardiovascular Procedures

Procedure Event Rate Event

CoronaryAngiography

1:1000 Death

Exercise TreadmillTesting

1:2500 MI or Death

SPECT Exam orRadionuclideVentriculography

1:1000 to1:10,000

Fatal Malignancy

ContrastEchocardiography

1:500,000 Death

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Pulmonary Hypertension

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Main ML, Hibberd MG, Ryan A, Lowe TJ, Miller P, Bhat G. Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent. JACC Cardiovascular imaging 2014;7:40-8.

Using propensity matching , CE associated with a 28% lower mortality at 48 h in comparison with patients undergoing nTTE

Interatrial Shunt

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Parker JM et al. Am J Cardiol2013;112:1039‐1045

Kalra A et al. JACC Cardiovasc Imaging 2014;7:206-7.

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Cost-effectiveness

Thx to Michael Main

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Technical capability and Operational excellence

Diagnostic capacity

Impact on diagnostic and prognostic thinking

Impact on therapeutic strategy

Cost effectiveness

Outcomes

Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies. CMAJ 1986; 134:587-594.

Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making 1991; 11:88-94

And yet contrast is underutilized

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Contrast Echocardiography as a Percentage of Total Echocardiography

0.00%

0.50%

1.00%

1.50%

2.00%

2.50%

3.00%

3.50%

4.00%

4.50%

5.00%

Arlington Medical Resources

FDA Black Box Warning

*through June 2015

Thx to Michael Main

Obstacles

• “Internal” (Lab operations)• Time • Orders• Consent• Personnel with IV skills / Scope of practice • Access to agent

• “External”• Cost considerations• Black box warning

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Decision Order/Consent

Personnel Agent MachineOptimization/ Protocols

STREAMLINE

Decision Order/Consent

Personnel Agent MachineOptimization/ Protocols

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Decision Order/Consent

Personnel Agent MachineOptimization/ Protocols

– Reduce/eliminate time to obtain order• Incorporate order for contrast into order for

echocardiogram

• Standing orders– a written document containing rules, policies,

procedures, regulations, and orders for the conduct of patient care in various stipulated clinical situations

• Develop policy for consent

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Order/ConsentDecision Personnel Agent

MachineOptimization/ Protocols

Decision Order/Consent

Personnel Agent MachineOptimization/ Protocols

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Decision Order/Consent

Personnel Agent MachineOptimization/ Protocols

• Optimize machine settings– Presets

• Agent specific

• Transducer specific

• Frequency specific

– Focal zone

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• Protocols– Infusion rate

– Look at more than the LV blood pool• RV

• Great vessels

• Doppler

• Resource person

Cost Considerations

“There is inadequate reimbursement to cover the cost of contrast “

Solutions:

For outpatient studies, there is reimbursement

Document guideline driven indication

For inpatient studies, cost of agent can be recaptured by reduction in other costs

Create/defend contrast budget

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Chest pain - angina?

LVEF (chemo)

LVEF for ICD or BiV

Stress echo

Pericardial disease

Valve disease

Aortic dissection

LV Thrombus

Atrial fibrillation

Hypotension

Dyspnea

Quality of Images

poor fair good

Indication for Study With thanks to Jonathan Lindner

Summary

• Contrast has been repeatedly shown to improve the accuracy and reproducibility of LV volume /EF assessment – Multiple off label uses

• Safety profile is excellent

• After “hit” triggered by black box warning utilization is increasing

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Summary

• Thoughtful approach to streamlining all steps in utilization chain is essential to optimal utilization and appropriate use of health care resources