1. Joseph L. Thomas MD FSCAI
Non-Invasive Diagnosis of Coronary Artery Disease with Acoustic Detection
Joseph L. Thomas MD FSCAI
Assistant Health Sciences Clinical Professor
David Geffen UCLA School of Medicine
Director, Interventional Cardiology, Harbor-UCLA Medical Center

2. Joseph L. Thomas, MD I Have Received Research Support:
I Have Received Research Support:
AUM Cardiovascular, Inc.

3. Decrescendo Murmur Associated with Critical LAD Stenosis
What’s Old is New
Detection of Turbulent Blood Flow is Common Practice
Auscultation of Carotid and Abdominal Bruits
Auscultation of Cardiac Sounds and Murmurs
Auscultation of Korotkoff Sounds
1967: Dock and Zoneraich Described “Dock’s Murmur”
Decrescendo Murmur Associated with Critical LAD Stenosis
Two Phenomena of Obstructive CAD
Pressure Drop Across a Stenotic Lesion (FFR, iFR, CT-FFR)
Disruption of Laminar Flow Across a Stenotic Lesion (AD)
Dock and Zoneraich. Am J Med 1967;42:

4. AD Evidence Development
Laminar coronary flow becomes turbulent beyond a stenosis
Reported frequencies associated with coronary turbulence
DB Cooper, Virginia Polytechnic Institute, December 2010 (thesis)

5. AD Evidence Development
Timing of discriminant frequencies identified
(200 – 300 msec after S2)
Akay M et al. Ann Biomed Eng 1992;21:
DB Cooper, Virginia Polytechnic Institute, December 2010 (thesis)

6. Summary of AD Development
Frequencies and Timing of Peak Coronary Turbulence
Competing Sound Spectra Identified, Excluded
Valvular, Lung Expansion, Ventricular Filling, Aortic Flow
Modern Signal Acquisition and Processing
Overcoming Insulation of Thorax, Environmental Noise
Allows Detection of Non-Laminar Flow Associated with CAD
Acoustic Detection , AUM Cardiovascular
Commercially Available Littman Electronic Stethoscope
Hard-Wired Data System with 1st Generation Analysis

7. AD Proof of Concept
Pre/Post-PCI of RCA

8. AD Proof of Concept
Abolition of Characteristic Early Diastolic Frequencies Post-PCI of RCA S2 S2 S1 S1

9. AD Clinical Experience
Study
Year
Design
Subjects (n)
Diseased/n
Result
MADHU 1
2004
LAD Disease Detection, Pre-Angio AD Testing 38
12/38 Subjects with LAD Disease
AD identified 9/12 accurately
MADHU 2
2006 51
18/51 Subjects with LAD Disease
AD accuracy 76%
ACOUSTIC
2012
CAD Detection, Pre-Angio AD Testing
165
65/127 Subjects with AD result had Disease > 50%
AD sensitivity 0.69 and specificity 0.77 for any stenosis >50%
MADHU 1, MADHU 2, unpublished data
ACOUSTIC, Wilson RF, European Society of Cardiology, 2012

10. ACOUSTIC AD Clinical Data
Positive AD
Negative AD
Total
FFR < 0.80 7 1 8
FFR > 0.80 3 12 15 10 13 23

11. CADence TM AD System Handheld Digital Stethoscope
Patient-Specific Booklet
- initializes study
- sequences test
Wireless Technology
Current System CE-Marked 2014
Enhanced Cloud-Based Signal Processing
- checks data quality - removes ambient noise
- extracts data associated with coronary turbulence
- graphs information - generates diagnostic report
- algorithms can be fine-tuned for sensitivity, specificity

12. CADence TM AD System Four Sites on Chest Wall
Testing Sequence
Four Sites on Chest Wall
Each Acquisition ~20 seconds
Requires Quiet Environment
Handheld Provides User Feedback

13. Digital Acoustic Device De-Identified Data Acquisition
CADence TM AD System
Diagnostic Report
Normal N
Diseased D
Inconclusive I
total test to report time = 20 min
Digital Acoustic Device
(CADence Device)
De-Identified Data Acquisition
(8 minutes)
Secure Cloud-Based
Big Data Analytics
(10 minutes)
Wireless Data Upload
(2 minutes)
Data preprocessing

14. TURBULENCE Clinical Trial
clinicaltrials.gov Identifier NCT
Double-Blinded Multicenter (15 Sites, US)
AD Accuracy Versus “Gold Standard” Nuclear Perfusion
Detecting ≥70% Stenosis in Vessels ≥ 2.5 mm
Detecting ≥50% Stenosis in LMCA
Non-Inferiority Design
Accuracy Validated Against CT/Conventional Angiography
Subjects with Chest Pain Undergoing Nuclear Stress Testing
≥ 2 CAD Risk Factors, Intermediate Risk
No Prior Revascularization or Q-Wave MI
Currently Enrolling (n = , Data Q1 2016)

15. CADenceTM Acoustic Detection
Transformative Technology
AD Works
Very Well or Well Enough? …To Be Determined
Role of AD
Diagnostic Test (Accuracy) or Gate-Keeper (NPV)
Potential Limitations
Functional Data Use in Broader Patient Groups
Anatomic Localization “Silent” Total, Subtotal Lesions
A Model for Future Medical Diagnostics
Miniaturized, Cost-Effective, Scalable Testing
Addressing Unmet Needs in Cardiovascular Disease

16. Thank You