Contrast Echocardiography

Contrast Echocardiography
Left ventricular opacification Myocardial perfusion Assessment of reperfusion and myocardial viability

Contrast Echocardiography

Improved endocardial border delineation reduced inter- and intraobserver variability improved detection of regional wall motion abnormalities improved calculation of LV volumes and ejection fraction

Contrast Echocardiography
Inter-institutional agreement according to image quality

Hoffmann et al. J Am Coll Cardiol 1996;27:330

Contrast Echocardiography

Contrast Echocardiography

Contrast Echocardiography
NA, 67 y.o. male

Contrast Echocardiography
NA, 67 y.o. male

Contrast Echocardiography
Effect of left ventricular opacification on accuracy of DbE

Dolan et al. Am Heart J 2001;142:908

Contrast Echocardiography

Left ventricular opacification Myocardial perfusion Assessment of reperfusion and myocardial viability

Contrast Echocardiography
Real-time perfusion imaging using power modulation

Contrast Echocardiography
MCE versusMIBI for assessment of myocardial blood volume

Wei et al. Am J Physiol 2001,280:H1896

How do we get from myocardial blood volume to myocardial blood flow ?

DYNAMIC IMAGING

Contrast Echocardiography
Quantification of myocardial blood flow

Contrast Echocardiography
Real-time perfusion imaging using power modulation

Van Camp et al., JASE 2003;16:263

Contrast Echocardiography
Real-time perfusion imaging using power modulation

Van Camp et al., JASE 2003;16:263

Contrast Echocardiography
Real-time perfusion imaging using power modulation

Van Camp et al., JASE 2003;16:263

Contrast Echocardiography
Real-time perfusion imaging using power modulation

Van Camp et al., JASE 2003;16:263

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male DIPYRIDAMOLEMCE

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
Dipyridamole real-time PowerModulation

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
MN, 50 y.o. male

Peltier et al. JACC 2004;43:257

Contrast Echocardiography
Dipyridamole RTCE: Prognostic implications

Tsusui et al. JCirculation 2005;112:1444

Contrast Echocardiography
Left ventricular opacification Myocardial perfusion Assessment of reperfusion and myocardial viability

Contrast Echocardiography
T.V.H. - F - 46 year old 10.43 am: ECG

Contrast Echocardiography
T.V.H. - F - 46 year old 11.43 am Coronary angiography

Contrast Echocardiography
T.V.H. - F - 46 year old 11.53 am Direct angioplasty and stenting

Contrast Echocardiography
Assessment of the no-reflow phenomenon by i.c.MCE

Ito et al. Circulation 1992;85:1699.

Contrast Echocardiography
Detection of myocardial viability with intravenousMCE

Swinburn et al. J Am Coll Cardiol 2001;38:19.

Contrast Echocardiography To Diagnose Acute Myocardial Infarction

The Problem
 

Over 5 million ED visits in US for chest pain (CP) Only 10-30% of them actually will have a AMI 10(acute MI) EKG diagnoses only 3030-40% of AMI Blood work, including troponins, take time to return Troponins take several hours detect after infarction

The Problem Part II



When AMI is not immediately diagnosed from EKG, treatment is delayed until troponins turn positive Many are admitted for rule out because their troponins are negative in ED Cost for rule out admissions is $10 billion in United States 5% of pts with AMI are inadvertently discharged

Wouldnt It Be Great


If there was a test immediately available to diagnose or risk stratify patients Low risk patients could be safely discharged without admission High risk patients could be admitted to the appropriate level of care and treated

The Contenders


There are a number of imaging modalities that try to address this problem
Traditional Echo SPECT CT MR

Each provides important information but has significant downsides

Traditional Echo

Traditional Echo


Traditional echocardiography is used to diagnose AMI by analyzing regional wall thickening and hypokinesis In patients presenting to the ED with CP and nonnondiagnostic EKG, specificity is only 53-57% for 53AMI and 78% for cardiac ischemia FalseFalse-negative studies reported in 1% of pts with AMI Poor image quality, especially in patients with suboptimal windows

SPECT

Non-transmural MI with stress induced ischemia

SPECT
  

TechnetiumTechnetium-99 used to evaluate myocardial blood flow (MBF) several hours after injection Effective at reducing rule out admissions by 32% Studies show good sensitivity and negative predictive value but performed using low-risk lowpatients and using CK or CK-MB as gold standard CK3-4% of LV myocardium must be affected before perfusion defect visible Hence small troponin-positive AMIs missed troponinSPECT unable to differentiate between old and new infarctions Downsides also include isotope issues and need for study to be performed in Nuc Med dept

CT

Multidetector CT showing a high-grade proximal LAD stenosis

CT


Benefits of being able to examine coronary anatomy, vessel stenosis, vessel remodeling, ventricular function and to exclude other serious causes of CP CT with calcium score good at diagnosing CAD but not whether CAD is causing CP Difficult to evaluate myocardium in the setting of tachycardia and previous stent placement Difficult to evaluate small arteries Pts exposed to radiation and contrast

Cardiac Magnetic Resonance

Sub-endocardial infarction in inferior left ventricular wall

Cardiac Magnetic Resonance



IV Gadolinium used to assess myocardial perfusion, wall motion abnormalities and coronary anatomy Benefits of high resolution, no radiation, no nephrotoxic contrast Drawbacks include motion artifact limiting evaluation of small arteries, limited availability of MR machinery, unsuitable for patients with pacemakers and pt claustrophobia Sensitivity 72% and specificity 87% compared to angiography

We Need Something Better



Ideal imaging modality would be:

Safe Highly specific and sensitive Having high negative and positive predictive values Not hampered by cardiac motion Able to be performed and interpreted at all hours Widely available Quick NonNon-invasive RadiationRadiation-free Portable Inexpensive

Introducing CE
 

Contrast Echocardiography Many benefits including:

Safety High specificity, sensitivity, negative predictive value, Good visualization despite cardiac motion Echo equipment is widely available Quick Non-invasive Non Radiation-free Radiation Portable Inexpensive

Side-BySide-By-Side CE, SPECT, MR

Fixed septal/apical perfusion defect after MI (arrows) with CE (left), SPECT (middle), and delayed enhancement with MR (right)

How It Works
 

Inject IV microbubbles Microbubbles remain exclusively intravascular and opacity systemic circulation Evaluate wall motion with traditional echo techniques Evaluate myocardial perfusion (described in a future slide)

About The Microbubbles



About 3 m in diameter
(Smaller than RBC)

  

Contain gases of low diffusibility and solubility Hemodynamically inert Microvascular rheology identical to RBCs
(Rheology is the study of the deformation and flow of matter under the influence of an applied stress.)

(Regional Function) RF


 

Easier to determine RF with CE than traditional echo because endocardial borders are delineated in much greater detail Even smaller wall motion defects are identifiable than with traditional echo Interpreter confidence is increased Interobserver and intraobserver variability is decreased

RF and Time Delay



The Dogma is that RF will only be abnormal in the setting of active CP The data show RF abnormalities persist after resolution of CP in NSTEMI, unstable angina and transient ischemia because of:
Patchy microvascular and myocellular necrosis Subocclusive disease with severe decreases in perfusion Myocardial stunning after spontaneous reperfusion

MBF


After regional function is analyzed, highhighenergy ultrasound is used to destroy the microbubbles How quickly microbubbles return depends on RBC velocity Microbubbles will return in 5 seconds in normal myocardium If microbubbles do not return in 5 seconds then myocardial perfusion is decreased

Another Image


Pt with recent AMI and occluded Cx. MP defects can be seen at the lateral apex and middle lateral wall

The Data: CE vs TIMI



Pts presenting to ED with CP and nonnondiagnostic EKG:

CE with RF and MP is superior to TIMI score, both with and without troponin values, in providing short-, intermediate- and long-term short- intermediatelongprognostic information (TIMI is Thrombolysis in MI scoring system based on age, coronary risk factors, known coronary stenosis, ST segment deviation, two or more angina events in previous 24 hrs, use of ASA in previous week, elevated troponin)

Visual Data

Incremental value of tests performed for determining risk of all events D=Demographics, C=Clinical, E=EKG

The Data: Effect of Time Delay



Patients presenting to ED within 12 hours of CP with non-diagnostic EKG: non No difference in detection of RF or MP abnormalities between pts with ongoing CP and resolved CP Time delay does not affect CEs ability to predict events within 24 hours

The Downsides


Smallest AMIs (about 1%) will be missed

These patients also had short duration of CP and low troponin peaks

Positive predictive value only 34% because old deficits unable to be differentiated from new deficits
PPV 98% if pts with previous of AMI excluded

Techs and MDs must be available to perform and interpret exams at all hours Interpretation is subjective

Example of CE in Use


81 yo man with well-controlled HTN and wellno prior cardiac hx Presents to ED with one hour of substernal CP, SOB, cramping in left arm Occurred after eating and not during significant exertion Normal PE, EKG, CXR, first troponin CE performed in ED

CE Saves The Day



CE in ED showed: RF abnormality in mid and distal septum, anterior wall and apex MP abnormality in same segments with gradual return of contrast indicating significant residual myocardial viability Pt admitted to cardiology, cath showed multi-vessel multidisease, CABG performed successfully Troponin was not positive until 8 hrs after presentation

Future Directions For CE



New contrast agents being developed that are targeted to inflammation, angiogenesis, thrombosis
Presence of acute inflammation one way to differentiate new from old injury

Use of new contrast agents may be expand contrast ultrasonography to any organ accessible by ultrasound

THANK YOU