1. The Ambulo 2400 Ambulatory Blood Pressure Monitoring System

2. Rationale for ABPM “White Coat Hypertension”
Anxiety of BP measurement in a clinical setting
Can elevate measurements as much as points higher than normal
An estimated 20% of the population exhibit this behavior (need reference)
Enables BP measurement during a patients normal activities
Provides a more complete picture of a patients hypertension profile
Evaluation of medication resistant hypertension
Enables measurement of BP over a wide range of time in order to evaluate medication effectiveness

3. Rationale for ABPM Evaluation of hypotension Nocturnal angina
Capture of events related to antihypertensive medications
Nocturnal angina
Investigate BP changes in patients during angina episodes
Preeclampsia
Evaluation of gestational hypertension or preeclampsia, especially in high risk pregnancies

4. Temperature & Humidity
Causes of BP Variance
Temperature & Humidity
Activity & Position
Food & Beverage
Lack of Sleep
Medications
Constipation
Hormones
Technique
Mood

5. Blood Pressure Facts BP changes with activity and position
BP drops in most people when supine & surges in the morning
Majority of heart attacks and strokes occur in morning hours
Most clinical trials make an assumption that everyone goes to bed and wakes up the same time
Incorrect calculation of BP results due to individual awake/asleep cycles impact on the quality of overall results

6. Blood Pressure Guidelines…
Critical marker in the determination of morbidity and mortality
Sustained hypertension can cause
heart attack, stroke, renal failure
Hypotension J-curve risk
Hypertensive
160
140
130
120
Hypertensive
Systolic
(mm/Hg)
Borderline
Pre-Hypertensive
Normal

7. Challenges of ABPM Measurement accuracy Patient comfort
Must be able to accurately measure blood pressure readings in a variety of environments
Should automatically determine sleep/awake cycles
Must meet industry standards for clinical accuracy
Patient comfort
Size and weight should allow patients to perform normal daily activity
Should operate quietly to allow normal sleep/awake patterns
Batteries should be capable of continuous operation for a minimum of 24 hours
Measurements captured and later uploaded for reporting and analysis

8. Challenges of ABPM Analysis Software Device configuration
Must be intuitive and require minimal training to operate
Downloading measurements
Generating graphs, reports and detailed statistics
Comparison to previous measurements including automatic sleep/awake pattern synchronization
Be HIPPA compliant
Should be capable of installation on “off the shelf” PC based hardware
Device configuration
Should allow customization based on patient population
Must require limited technical knowledge or expertise

9. Circadian Rhythm and BP Measurement
Heart rate and blood pressure both exhibit a strong circadian pattern with values for blood pressure, heart rate, and rate
“Dippers” is used to describe patients whose nocturnal pressure drops at least 10% below their daytime pressure
“Nondippers” is used to describe patients for whom the nocturnal decline in blood pressure is blunted or absent.
Recent studies suggest that nondippers appear to have an increase in cardiovascular morbidity
In both normotensive and hypertensive individuals, blood pressure and heart rate fluctuate according to both mental and physical activity levels, especially during wakefulness and sleep.
In most hypertensive patients, there is a rather marked rise in blood pressure upon awakening that is called the morning or "a.m." surge

10. Examples of Circadian Profiles….
Normotensive
Day: 128/79
Night: 110/62
Hypertensive Non-Dipper
Day: 210/134
Night: 205/130
White Coat
Office: 175/95
Day: 133/71
Night: 119/59

11. Approaches in BP Measurement
Home BP
Office BP
Ambulatory BP
Central BP
ECG Equivalent --
12-Lead
Holter
Obtaining a BP measurement
Yes
Assessing White Coat & Masked Effects
Limited
Identifying Circadian Pattern No
Identifying diurnal or nocturnal rhythm
Identifying true or mean pressure
Central
Evaluating extent of nocturnal dip and morning surge
Determining extent of variability
Evaluation of response to treatment
Determining time dependent effects of treatment – including Phase I cardiac safety trials
Yes†
Correlation of activity to BP
Accuracy of recorded data
Evaluation of central pressure, arterial stiffness and pulse wave velocity

12. Ambulo 2400 System….
Form Factor: Compact, durable and easy to use by patients and investigators which leads to better compliance & data
Precise: Highly accurate, and robust oscillometric algorithm based on patented digital signal processing techniques
Easy to Wear Options: Integrated on the blood pressure cuff, clipped on the hip or strapped around the shoulder
Actigraphy: Automatic categorization of sleep/awake cycles based on patented technology reduces reliance on diaries
Validated: Validated according to the AAMI SP-10 and ISO80601 standards plus British Hypertension Society’s protocols (A/A grade) including in pediatrics & adolescents
Software: Sophisticated, intuitive and open software interface for easy programming, data download as well as report generation

13. Specifications…. Size Weight Measurement Ranges Measurement Accuracy
119 mm × 68 mm × 32 mm (4.7”x2.7”x1.2”)
Weight
253 grams (9 oz.)
Measurement Ranges
Systolic 60 to 280 mmHg
Diastolic 30 to 200 mmHg
Pulse Rate 30 to 180 bpm
Measurement Accuracy
Blood Pressure:±5 mmHg mean diff.
±8 mmHg std. dev.
Heart Rate: ±3 bpm
Measurement Intervals
Four adjustable intervals
0, 5, 10, 20, 30, 45, 60, 90, or 120 min.
Optional randomization up to ±75%
Optional Sequential Plans for Phase 1 Cardiac Safety Trials
PC Interface
USB cable with mini-B connector
Cuffs
Standard Adult, Large Adult & Child
Optional EasyWear™ Adult
Actigraphy
Recording of 3-axis of motion via accelerometer
Display & categorization of sleep/awake cycles via application software
Memory
Solid-state Flash technology.
Sufficient for 2700 blood pressure measurements and 7 days of Actigraphy
Batteries
2 AA batteries NiMH
Current: 610mA (max); 1.3 mA (idle)
300 measurements using two 1600mAh NiMH batteries on regular adult cuff

14. Easy to Wear Options….

15. Independent Clinical Validation….
New global standard for development and validation of all blood pressure devices
Clinical validation of Ambulo 2400 in 85 adults, adolescents and pediatrics
Performed by Dr. Bruce Alpert of the University of Tennessee in Memphis
Published in “Blood Pressure Monitoring” journal in Sept (PubMed ID: )

16. Importance of Actigraphy in ABPM….
The Problem
The Solution
BP changes with activity and position
BP drops in most people when supine & surges in the morning
Majority of heart attacks and strokes occur in morning hours
Most clinical trials make an assumption that everyone goes to bed and wakes up the same time
Incorrect calculation of BP results due to individual awake/asleep cycles has huge impact on the quality of overall results
Built-in Actigraphy monitoring based on X, Y & Z accelerometer
Automatic calculation of awake/asleep over 24 hour period
No need for subject diaries
Higher quality BP data

17. BP Profile of Patient…
Systolic
Dip
15%
Asleep
10:00 PM
Awake
7:00 AM

18. Corrected based on Actigraphy….
Systolic
Dip
22%
Asleep
02:10 AM
Awake
9:10 AM

19. Ambulo 2400 Software…

20. Ambulo 2400 Software…
Intuitive & Feature-Rich Solution
For Windows® based platforms (XP, Vista & Windows 7)
Allows for configuration of the device including “One Click Configuration”, testing and calibration
Measurement download after the procedure
Generation of detailed tabular, graphical and statistical data
Support for AHA/JNC7 and ESH guidelines
Special features for pediatric patients
Customized reports in Microsoft® Word, HTML or PDF† formats
Comparison reports between measurement sets including automatic sleep/awake pattern synchronization
Data import/export in XML or CSV (Excel-compatible)
Assist with HIPAA compliance
Available in English, Spanish, French, Turkish, Greek, Finnish, Portuguese
† PDF report generation requires 3rd party utility available for free

21. Global CPT & ICD-9 Codes….
CPT:  Ambulatory blood pressure monitoring; including recording, scanning analysis, interpretation and report.
High blood pressure without hypertension
(The only ICD-9 code covered by Medicare – Ranges from $60 – $90 for US patients)
796.2
Syncope, or near syncope
780.2
Weakness (generalized)
458.9
Hypotension, unspecified
785.50
Cardiovascular collapse
458.0
Orthostatic hypotension
402
Hypertensive heart disease
429
Cardiovascular disease due to hypertension
429.2
Resistant hypertension
997.91
Hypertensive renal disease
403.1
Unspecified hypertension complicating pregnancy
642.9
Transient hypertension of pregnancy
642.3
Mild preeclampsia
642.4
Maternal hypotension syndrome
669.2

22. Competitive Landscape

23. Global Competitive Landscape…
Manufacturer/ Product
Mortara
Ambulo 2400
SunTech
Oscar 2†
Spacelabs
90207 / 90217
A&D
TM-2430
Size
11.9x6.8x3.2 cm
12x7x3 cm
11.4x8.6x2.8 cm
10x7x2.5 cm
10x7.2x2.7 cm
Weight
253g
284g
347g / 255g
215g
BP Algorithm
Oscillometric
Interface
USB
Serial / USB
Serial/Modem/Printer
Serial
Configuration
4 Periods or
Sequential Plans
3 – 6 Periods
4 Periods
6 Periods
Validation Adult
AAMI SP-10, BHS (A/A) & ISO
AAMI SP-10, BHS & EHS
AAMI SP-10 & BHS (B/B)
90207 BHS Grade: B, C & D
AAMI SP-10 & BHS
Validation Pediatric
AAMI SP-10, BHS (B/B) & ISO
AAMI SP-10, BHS (C/D) & ISO
Actigraphy
Yes -
Cuffs & Replacement Costs
3 + EasyWear
Optional disposables
Regular & Large
Regular + Large
Batteries
2 NiMH AA’s
4 / 3 Alkaline AA’s
3 Alkaline or NiCad
Memory
Flash; BP’s & 7 days Actigraphy
Flash; 250 BP’s
~250 BP’s, Battery Backed RAM
300 BP’s

24. Global Competitive Landscape…
Manufacturer/Product
Mortara
Ambulo 2400
SunTech
Oscar 2
SpaceLabs
90207 / 90217
A&D
TM-2430
Software
Hypertension Diagnostics Suite
AccuWin Pro v3
(WA: CardioPro)
RMS
DoctroPro
Warranty
2 Years + Optional Damage Protection
2 Years + Extended
(WA: 1 Year)
2 Years
Origin
USA
USA/China
Japan
Mortara’s Advantages to Emphasize vs. Each Competitor
No Actigraphy, expensive device and replacement cuffs; no support for clinical trials
Dated technology; bad software; expensive device and replacement cuffs
Dated technology; bad software; expensive replacement cuffs
Competitor’s Key Claims & Advantages
Soft Orbit Cuffs
Distribution base Software
Established Base in Clinical Trials Market
Distribution base
Aggressive pricing

25. Global Competitive Landscape…
Manufacturer/ Product
Tiba Medical
Ambulo 2400
IEM
Mobil-O-Graph
Microlife
WatchBP 03
Size
11.9x6.8x3.2 cm
128mm x 75mm x 30mm
9.8x6.8x2.9 cm
Weight
253g
240 g
240g
BP Algorithm
Oscillometric
Interface
USB
USB and Bluetooth
Configuration
4 Periods or
Sequential Plans
7 Predefined, 2 variable
2 periods
Validation
AAMI SP-10, BHS (A/A) & ISO
BHS (A/B), AAMI
AAMI SP-10
ESH
Actigraphy
Yes No
Cuffs & Replacement Costs
3 + EasyWear
Optional disposables
Sm. Adult, Adult, Lg, Adult -
Batteries
2 NiMH AA’s
2 AA
Medium & Large
Memory
Flash; BP’s & 7 days Actigraphy
300
4 AAA

26. Global Competitive Landscape…
Manufacturer/Product
Mortara
Ambulo 2400
IEM
Mobil-O-Graph
Microlife
WatchBP 03
Software
Hypertension Diagnostics Suite
WatchBP Analyzer
Warranty
2 Years + Optional Damage Protection
2 years monitor, 3 mos. Access.
2 Years
Origin
USA
Germany
Mortara’s Advantages to Emphasize vs. Each Competitor
No Actigraphy, expensive device and replacement cuffs; no support for clinical trials
No Actigraphy; not enough power to support long term or large arm measurements
Competitor’s Key Claims & Advantages
Blue-tooth capability, Client Server mgt sys, Suite of products- stabilo-graph for upper arm and clock- wrist bp, Auto Feedback Logic (dynamic inflate)
Aggressive pricing based on Made in China

27. SunTech
The SunTech Medical, Inc. patented Orbit cuff uses an innovative stretch-sleeve design to maintain cuff placement and promote patient comfort.
The Oscar 2 is a light, compact monitor that uses motion tolerant algorithms to reduce re-inflates and failed readings. The auto-intelligent inflation pressure also reduces measurement time, promoting patient comfort by controlling cuff inflation.
Weakness
No Actigraphy, cost is higher than most

28. IEM Claimed Clinical Advantage
AFL (Auto Feedback Logic)* ensures unsurpassed measurement acceptance and patient comfort                                                 
Individually adjusted cuff inflation (AFL) provides a key advantage for patients: the ability to enjoy an uninterrupted night’s sleep. This means that measuring blood pressure is faster and more patient-friendly. Wearer comfort (device compliance) is superior to that of competitor products, with correctly adjusted and washable one-hand cuffs.
AFL* ensures a much better night’s sleep
Weakness
Pulse Wave velocity does not work according to several white papers addressing this study.

29. SpaceLabs Claimed Clinical Advantage
Fast, accurate results from Spacelab's ABP system enable you to fine-tune your patients’ treatment and better assess their cardiovascular risks. Its reliability has made it the #1 ABP monitor in the world, preferred by physicians and patients alike. Its latest software supports compliance with government requirements for integrity, availability, security and confidentiality of patient health information.
Weakness
The and ABPM devices have been available since 1995 with no apparent changes to the SW and the engineering team have all left SpaceLabs. Although at one time considered to be the “Gold Standard”, Many other companies have exceeded the BHS rating of SpaceLabs as the AMBULO 2400 received an A rating in all areas of both adult and pediatric while SpaceLabs has maintained a grade of B and C rating.

30. Current Clinical Research Customers…
Buffalo Clinical Research Center
Netherlands
Cancer
Institute