MCG Score A New Biomarker for Ischemic Heart

What is MCG Score ? • MCG Score is a new biomarker which reflects patient ischemic condition. • Ischemic Heart Disease (IHD) such as angina and myocardial infraction can be measured by MCG score • MCG Score can be used as biomarker for heart disease just like as other biomarker such as “blood glucose level”, “uric acid level” and “blood pressure”. Diabetes Blood glucose level Over 126 mg/dl Gout Uric acid level Over 7. 0ｍｇ/ｄｌ IHD MCG Score Over 4. 0 Confidential 2 © 2013 Premier Heart Japan, Inc. , All rights reserved

How MCG score works ? • Non-invasive test within 10 -20 minutes • The risk of IHD is reported in score level from 0 to 20 • MCG score will change as the patient condition change • Patient condition can be monitored with MCG score. Confidential 3 © 2013 Premier Heart Japan, Inc. , All rights reserved

MCG Score How Reliable ? • MCG score is US FDA authorized • US CPT insurance Code (0206 T) • Peer Reviewed Papers Circulation Confidential ESC 2012 © 2013 Premier Heart Japan, Inc. , All rights reserved

MCG Score How Reliable ? ・ The study for MCG is presented in the major cardiac and other conferences such as ACC and ESC. （ACC, 2011) ・Paired-Comparison of the Resting Multifunction Cardiogram (MCG) With Stress Sestamibi SPECT Myocardial Perfusion Imaging In The Detection Of Relevant Coronary Stenosis (>70%) ・Accuracy of the Resting Multifunction Cardiogram (MCG) in Detecting the Presence or Absence of Relevant Coronary Stenosis (>70%) in Women. （ESC, 2012）・Non Invasive Assessment of Relevant Coronary Occlusion through Mathematical Analysis of Spectral ECG Components (MCG) with comparison with Coronary Angiography in Symptomatic Patients （Conference of Japan Diabetic Society, 2012) 「Detection of Ischemia for type 2 diabetes patients by using the Multifunctional Cardiography（MCG）」（Conference of Japan medical check up Society, 2010）「Multifunction Cardiogram(MCG) for Medical Check up」 Confidential 5 © 2013 Premier Heart Japan, Inc. , All rights reserved

MCG Score How Reliable ? ・Double blinded trial in 7 countries 1, 076 patients comparing against CAG. Sensitivity over 90% and Specificity over 80% for over 70% coronary occlusion. “Comparison of a Two-Lead, Computerized, Resting ECG Signal Analysis Device, the Multi. Function-Cardio. Gramsm or MCG (a. k. a. 3 DMP), to Quantitative Coronary Angiography for the Detection of Relevant Coronary Artery Stenosis (>70%) - A Meta-Analysis of all Published Trials Performed and Analyzed in the US. ”（International Journal of Medical Sciences, 2009; 6(4): 143 -155） Confidential 6 © 2013 Premier Heart Japan, Inc. , All rights reserved

MCG Score How Reliable ? MCG Score comparison Nuclear Stress Imaging presented at ACC MCG score showed much higher sensitivity and specificity for patients ischemic condition Confidential 7 © 2013 Premier Heart Japan, Inc. , All rights reserved

Comparison MCG Score vs Angiogram Gender Age F 64 LAD #6 #7 Confidential Ischemia

Comparison MCG Score vs Angiogram Gender Age F 84 LAD #9 #10 Confidential Ischemia

Comparison MCG Score vs Angiogram Gender Age M 49 CX #11 #12 Confidential Ischemia

What MCG is looking at? Frequency Analysis ECG PW PW TIme Confidential MCG FFT

What MCG is looking at? Frequency Analysis ECG MCG Auto Power Spectrum Confidential Coherence

ECG tracing with Lead V 5 19 year old patient with No CAD* Confidential 97 (Male) patient with TVD** 13 © 2013 Premier Heart Japan, Inc. , All rights reserved *CAD, Coronary Artery Disease ** TVD, Triple Vessel Disease

Auto Power Spectrum 19 y. o. (Female) with No CAD Lead V 5 97 y. o. (Male) patient with TVD Lead V 5 ・ The Auto power spectrum is a measure of the power in watts of each frequency of an ECG signal. ・ The peak with the lowest frequency in APS* represents the heart rate. ・ APS data can be used to identify pathological conditions such as fast or slow heart rate, arrhythmias, and fibrillation. ・ The peak - to - peak power amplitude abnormal distribution correlates well with clinical conditions such as myocardial ischemia hypertensive heart disease, congestive heart disease or cardiogenic shock. Low third and/or fourth peak Lead II Low first peak Confidential 14 © 2013 Premier Heart Japan, Inc. , All rights reserved *APS, Auto Power Spectrum

Coherence Function 19 y. o. (Female) with No CAD 97 y. o. (Male) patient with TVD Low first peak Low coherence of the transfer function ・ The coherence function represents the correspondence of amplitude, frequency and phase shift of ECG (V 5 and II) leads. ・ The coherence function is expressed as the amplitude ratio of the two leads squared for each frequency, the result is a measure of the correspondence of the output energy of the two leads. ・ The cross correlation data can be used to find evidence of dysfunction in cardiac electrical condition patterns or cellular responses adapting to abnormal blood supply, particularly in relation to myocardial remodeling such as © 2013 Premier Hearttrauma Japan, Inc. , All rights reserved ventricular hypertrophy and myocardial infarction, surgical injuries or blunt chest causing contusion. Confidential 15

Phase Shift 19 y. o. (Female) with No CAD 97 y. o. (Male) patient with TVD A sharp oscillation of phase shift wave forms Reflects time delay between different myocardial fibers within a part of the heart due to coronary artery blockage and MI*. ・ The face angle shift function is the comparison of an actual waveform (the auto power spectrum of each lead) to an ideal waveform (the cross power spectrum of two leads), and expressed as the angle in degrees of the phase shift for each frequency. This is essentially the relative angles of harmonics at a specific frequency to each other. ・ The angle represents the delay between the two leads, so that a greater angle is evidence of higher degrees of asynchronization. • The positive angles indicate angle shift favoring the input lead (V 5), and negative angles indicate angle shift favoring the output lead (II). ・ Asynchrony between the leads may be due to infarction, myocardial ischemia myocardial hypertrophies. © 2013 Premierand Heart Japan, Inc. , All rights reserved Confidential 16 *MI, Myocardial infarction

Impulse Response 19 y. o. (Female) with No CAD 97 y. o. (Male) patient with TVD High amplitudes with latency greater than 10 ms indicate excessive oscillation ・ The impulse response function is used to measure the quality of the system. ・ Impulse response data can be used to detect changes in the cardiac muscle and in blood flow, including ventricular remodeling, increases or decreases in myocardial compliance, conduction blockage or delays and potential arrhythmia. ・ Distortion in the impulse response can indicate part of the cardiac cycle not visible in the conventional ECG © 2013 Premier Heart Japan, Inc. , All rights reserved signal including hidden arrhythmias Confidential 17

Pre and Post PCI/Stenting Example Confidential 18 © 2013 Premier Heart Japan, Inc. ,

Pre and Post PCI/Stenting Example (Auto Power Spectrum) l A Male Patient with Bi-Vessel Disease § This pair of power spectra belong to a male patient who was diagnosed with severe two vessel disease and Type II DM. § He received PTCA/Double Stenting for two critical RCA stenosis with remaining RCX having a 50% lesion. Pre-intervention he had a MCG disease severity score of 8 with global ischemia. Following his intervention his MCG severity score decreased to 2. 5 with mild global ischemia. 40 - Post Stenting Pre Stenting No symptoms sample Confidential 19 © 2013 Premier Heart Japan, Inc. , All rights reserved

Pre and Post PCI/Stenting Example （Phase Shift） l A Male Patient with Bi-Vessel Disease § This pair of phase shift functions belong to the same male patient who was diagnosed with two vessel disease. § The differences in both the power spectra (previous page) and phase shift functions pre- and postintervention are discernable and calculable by MCG. Post Stenting Pre Stenting No symptoms sample Confidential 20 © 2013 Premier Heart Japan, Inc. , All rights reserved

MCG Signal & Digital Data Processing Decryption FFT Leads II & V 5 recorded for 82 sec Signal average of 16 segments at 5. 12 sec @ 100 Hz Amplified, digitized, encrypted & transmitted Six mathematical transformations Local Client Gxx Pih 2 xy Vxy Automatic diagnostic report (PDF file) Identification of 166 indices Final Diagnosis Severity Score Pattern matching in 40, 000 patient database Txy Premier Heart Network Operation Center (NOC) where the web-based MCG database is housed Confidential 21 © 2013 Premier Heart Japan, Inc. , All rights reserved

Benefits from MCG Score 4 At Clinic Fast, Accurate, Non Invasive • Screening Bio Maker for patient with symptom or high risk • Patient periodical check up for prevention Additional Service Patient Monitoring Low Cost 4 At ER • Additional Accurate Bio Marker to decide whether to admit or not • Monitoring Bio Marker Fast and Accurate Confidential Tie Breaker © 2013 Premier Heart Japan, Inc. , All rights reserved

What you can do with MCG Score • Increases diagnostic accuracy for IHD • Monitor Patient with MCG score for your treatment • Additional Service for Early Detection and Prevention • Networking local clinics and Cardiology Department • Improve financial situation Confidential © 2013 Premier Heart Japan, Inc. , All rights reserved