Contrast Echocardiography. What is the critical need? Meets a critical need! Cavity Opacification. What contrast is approved for: chamber assessment?

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1 Contrast Echocardiography for LV Opacification Natesa G. Pandian What contrast is approved for: Cavity Opacification Meets a critical need! Disclosure: Speakers Bureau, Lantheus Inc What is the critical need? A Problem in Transthoracic Echocardiography Best echo Dr. Roger Click has ever done What percent of your TTE Studies are technically suboptimal for chamber assessment? a) < 10% b) 10-20% c) 20-40% d) 40-60% What percent of your TTE Studies are technically suboptimal for chamber assessment? a) 0%, we are so good! b) < 5% c) < 10% d) 10-20% e) 20-40% f) 40-60% g) 90% of our studies are hopeless!

2 Clinical Reality: One quarter of adult TTEs Are technically suboptimal for LV (and RV) function assessment Intensive care unit One third to almost half of Stress Echo studies are suboptimal Accurate LV function assessment has major implications Diagnosis Prognosis Medical therapy Interventional therapy Surgerical therapy Accurate LV function assessment has major implications Diagnosis Prognosis Medical therapy Interventional therapy Surgerical therapy Need help! Ultrasound Contrast Agents in US Definity μ Lipid shell Perflutren gas Optison μ Albumin shell Perflutren gas

3 Bubble Response to Ultrasound Bubble Response to Ultrasound MI = Mechanical Index MI Bubble Response Acoustic Effect Clinical Use Measure of Ultrasound Input Power < >1.0 Bubble Response to Ultrasound Bubble Response to Ultrasound MI Bubble Response Acoustic Effect Clinical Use MI Bubble Response Acoustic Effect Clinical Use <0.1 Linear Oscillation Backscatter Enhancement Fundamental LVO, Doppler <0.1 Linear Oscillation Backscatter Enhancement Fundamental LVO, Doppler Nonlinear Oscillation Harmonic Backscatter Harmonic LVO Real-time Perf >1.0 >1.0 MI <0.1 Bubble Response to Ultrasound Bubble Response Linear Oscillation Acoustic Effect Backscatter Enhancement Clinical Use Fundamental LVO, Doppler Definity - Clinical Trials Safety and Tolerability 1716 subjects evaluated: Mean age 56.1 years Incidence of adverse events similar across all demographic groups Nonlinear Oscillation Harmonic Backscatter Harmonic LVO Real-time Perf Safety, Tolerability and Efficacy >1.0 Disruption Destruction Transient Har Signals Doppler Triggered Perf Well-Established

4 Should I be afraid of major complications? DEFINITY has a proven safety profile in high risk hospitalized patients Kusnetsky L et al: 1 The results of a retospective study of 18,671 consecutive echocardiographic studies on hospitalized patients showed no increased risk of mortality Main M et al: 2 A multicenter registry risk adjusted study in 4,300,966 patients showed that there was no difference in overall mortality rates between patients undergoing DEFINITY - enhanced echo and patients undergoing unenhanced echo Clinical Trials Safety and Tolerability Most Frequent Treatment-related Adverse Events (occurring in 0.5% of subjects) (N = 1716) n (%) Administration of echo contrast did not induce any significant change in vital signs, physical examination, and ECG. No death, acute myocardial infarction or other cardiovascular events occurred during the echocardiographic examination or the remaining hospitalization period The only minor events observed were transient injection site hypersensitivity (2.6%) and transient back pain (1.7%) These data provide evidence on the safety of contrastenhanced echocardiography in the first 24 h of AMI Headache 40 (2.3) Back/renal pain 20 (1.2) Flushing 19 (1.1) Nausea 17 (1.0) Chest pain 13 (0.8) Dizziness 11 (0.6) Injection site reactions 11 (0.6) Number of subjects reporting 144 (8.4) at least one adverse event 1. Nucifora G et al. Eur J Echocardiogr. 2008;9(6): In whom I will not give Definity? Previous reaction Pregnancy Known severe Pulm HTN Obvious significant shunt DEFINITY Pulmonary Hemodynamic Study Normal (PASP<=35mmHg) N=16 Pulm Htn (PASP>35mmHg) N=16 No change in PASP post-dose Wei et al

5 DEFINITY Pulmonary Hemodynamic Study No change in PASP associated with DEFINITY No deaths or SAEs No change in immunological parameters (C3a, C5a, tryptase, IL-6) How about PFO? No issues in the original safety studies. We don t exclude them. Lipid Shell Agent - Administration How to Use it? The lipid shell agent is supplied as a single use 2-mL clear glass vial containing clear liquid Activate the product Bolus: 10 microl in sec, followed by a 10 ml saline flush. If necessary, a second 10 μl/kg dose followed by a second 10 ml saline flush 30 minutes after the first injection Infusion: 1.3 ml in 50 ml of preservative-free saline, at 4.0 ml/min, titrated as necessary, not to exceed 10 ml/min. The maximum dose is either 2 bolus doses or 1 single infusion. Imaging: Mech Index should be set at 0.8 or below How to Use it? The protein shell agent is supplied as a single use 3-mL vials Protein Shell Agent - Administration The recommended dose is 0.5 ml injected into a peripheral vein. This may be repeated for further as needed. 1. The injection rate should not exceed 1 ml per second. 2. Follow with a flush of 0.9% saline or 5% Dextrose Inj 3. The maximum total dose should not exceed 5.0 ml in any 10 minute period. 4. The maximum total dose should not exceed 8.7 ml in any one patient study

6 Patient history 58-year-old man Presented with symptoms of exertional dyspnea Physical examination: faint heart sounds, no murmurs EKG: T-wave inversion in the anterior precordial leads Echocardiogram was ordered to assess LV function 1. Normal 2. WMA: Hypo/Akinesis/Dyskinesis 3. Hyperkinetic 4. Not sure, Need help 1. Normal 2. WMA: Hypo/Akinesis/Dyskinesis 3. Hyperkinetic 4. Not sure, Need help

7 Contrast enhanced image Why this diagnosis is important? Patient history 25-year-old man Presented with dizzy spells Clinical history Physical examination: normal Rest EKG: Normal Ambulatory EKG monitoring: Nonsustained ventricular tachycardia Echocardiogram was ordered to assess LV function LV Apex 1. Normal, just a drop-out 2. Ischemic LV aneurysm 3. Pseudoaneurysm Unenhanced 4. LV diverticulum 5. Not sure, Need help

8 Contrast enhanced image Why this diagnosis is important? Question of LV thrombus Patient history 52-year-old woman Presented with shortness of breath Clinical history Past myocardial infarction Physical examination: No abnormal findings Echocardiogram was ordered to assess LV function

9 1. Definitely a clot 2. Probably a clot Contrast enhanced image 3. Definitely No clot 4. Probably No clot Another question of clot 1. Yes, thrombus 2. No thrombus 3. Need help Contrast enhanced image

10 1. Yes, thrombus Contrast enhanced image 2. No thrombus 3. Not sure, Need help Patient history 55-year-old woman to PCP HF symptoms JVP elevated, Leg edema Normal EKG: Nonspecific changes Blood tests ordered Pt sent for echo Contrast enhanced image

11 Patient history 63-year-old man to PCP CABG 5 years earlier Dyspnea on exertion Obese individual JVP elevated, Leg edema EKG: Nonspecific changes Pt sent for echo Contrast enhanced image Pt with Aortic Stenosis Denies symptoms Can t walk on a treadmill

12 How severe is AS? Contrast enhanced image Admission with extreme dyspnea Intubated CTPA: Negative Contrast enhanced image Look at the whole picture RV Function? Normal Mildly impaired Severely impaired Not sure

13 Contrast enhanced image RV function Contrast for Doppler Record Doppler during wash out Small amount of contrast is enough Decrease the gain Not a substitute for a bad angle Contrast enhanced image

14 Contrast enhanced image Baseline Non-contrast Study Rest Stress Contrast enhanced images

15 Patient undergoing interventional radiology procedure under sedation Sudden run of Ventricular Tachycardia EKG performed Cath labs occupied Contrast enhanced image

16 Coronary Arteriography LV Angiogram Why this diagnosis is important? 3D Stress Echo Aid of Contrast NGP_P

17 Septal Ablation in HOCM Pitfalls

18 Optimizing instrument settings for contrast use Acceptable LV border delineation also depends on imaging with appropriately adjusted system settings 1 Control Features Setting 2 Focus Adjusts beam focus Mid to near field 46 Managing artifacts with contrast Swirling Avoid through: Decreasing MI Adjusting focus Increasing dose if caused by poor LV function 47 Transmit power Regulates ultrasound intensity MI Receiver gain Boosts echo amplification High Compression (dynamic range) Gives 2D grayscale display Wide/high Attenuation Avoid through: Administering contrast as a slow infusion/bolus followed by a slow flush Stopping the injection process and waiting until it clears Impact of Contrast Echocardiography on Evaluation of Ventricular Function and Clinical Management in a Large Prospective Cohort Kurt et a. JACC 2009; 53: consecutive patients Uninterpetable decreased 11.7 to 0.3% Thank you Impact on management: 35.6% Savings $122/pt