1 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. © 2014 HeartWare, Inc. CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. TM00017 Rev03 02/14 Module 1/10 HeartWare ® Ventricular Assist System Introduction & Theory of Operation

2 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Objectives Discuss key characteristics of the HVAD ® Pump Describe HVAD Pump principles of operation including: –Blood Flow Characteristics and HQ Curve –Flow Estimation Algorithm –Ventricular Suction Detection Alarm Identify recommended operating parameters

3 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Centrifugal, continuous flow pump (160g) Integrated inflow allows the device to sit next to the heart with outflow attachment to the ascending aorta Capable of delivering up to 10 L/min flow Flow Channel Center Post Wide Blade Impeller Inflow Cannula Front Housing Ceramic Disk Rear Housing

4 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Suspension: Magnetic and Hydrodynamic Wide-blade impeller is magnetically and hydrodynamically suspended Speed range: RPM HVAD Pump flow is preload dependent and afterload sensitive

5 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Motor Stators & Suspension Motor stators contained in the front and rear housings Motor stators provide the active magnetic force that helps run the pump Hydrodynamic thrust bearing generates a fluid film on which the rotating impeller slides (bearing “lifts” the impeller off the housing)

6 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Washes underside and center-post regions Provides fluid “cushion” & washes thrust bearings Washes flow channels and immediately enters outflow graft Impeller and Fluid Flow: Three Flow Paths Primary flow path Secondary flow path Tertiary flow path

7 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device RPM Speeds above 3200 increase the risk of suction events Speed Range: 1800 – 4000 RPM RPM Should only be used during implant procedure when weaning from CPB HVAD ® Pump Operating Guidelines Recommended clinical operating speed range: 2400 – 3200 RPM Recommended clinical operating speed range: 2400 – 3200 RPM Speed (RPM) Power (watts) Flow (L/min)38

8 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Operating Characteristics Pump Head-Flow Curves (HQ) dictate how much flow is impacted by preload and afterload H = Differential Pressure (afterload – preload) Q = Flow The shape of the HQ curves is different for every pump design; these differences impact the pump’s behavior

9 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Flow (L/min) Differential Pressure (mmHg) 1800 RPM 2400 RPM 3000 RPM 3600 RPM 4000 RPM HQ “performance curves” dictate how much flow will be provided for a given differential pressure (AOP – LVP) and pump speed ΔP = 75 mmHg Speed = 2400 RPM Flow = 4 L/min HVAD ® Pump Operating Characteristics

10 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump HQ Curves H1: Preload (LVP) ↑ then differential pressure ↓ and Flow ↑ - Increased venous return H2: Afterload (AOP) ↑ then differential pressure ↑ and Flow ↓ - Increase in MAP Example: If AOP 75mmHg & LVP 10 then H = 65mmHg If LVP increases to 15, then H = 60mmHg If AOP increases to 95, then H = 85mmHg Differential Pressure = Afterload – Preload ΔP = AOP - LVP Differential Pressure = Afterload – Preload ΔP = AOP - LVP

11 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Operating Characteristics Conditions that may lead to a decrease in preload: –Compromised right ventricular volume (e.g. RVF, Tamponade) –Low intravascular volume –Increase in pump speed (a volume/speed mismatch) A reduction in preload may lead to: –Reduced VAD Flow –Reduction in Cardiac Output –Suction condition Conditions that may lead to an increase (or high) afterload: –Increased system vascular resistance –Increased pump speed A high afterload may lead to: –Retrograde flow –Reduced VAD flow –Reduction cardiac output Preload Afterload

12 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Physiologic Differences of Centrifugal (HVAD ® Pump) and Axial Continuous Flow Pumps 1 1 Moazami, et al (2013). Axial and centrifugal continuous-flow rotary pumps: A translation from pump mechanics to clinical practice. J Heart Lung Transplant 2013;32:1–11 Significantly higher flow pulsatility Significantly higher estimated flow accuracy Significantly lower inlet suction at low flow conditions Not as easily scaled down to sizes sufficient to be implanted intravascularly Both centrifugal and axial pumps have low preload sensitivity relative to the native ventricle Both centrifugal and axial pumps have high after-load sensitivity relative to native ventricle; however, centrifugal pumps, by hydraulic performance characteristics, have higher after-load sensitivity

13 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Flow Estimation LVAD flow estimation depends upon: 1)Pump speed 2)Power 3)Patient’s blood viscosity LVAD flow estimation depends upon: 1)Pump speed 2)Power 3)Patient’s blood viscosity

14 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Flow Estimation The HVAD Flow Estimation algorithm uses “look-up tables” to calculate flow Each “look-up-table” contains corresponding speed and flow points & is gradated to correspond to a 0-50 % equivalent HCT range 0% 10% 20% 30% 40% 50% HCT

15 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Flow Estimation The correlation between actual and estimated flow is R 2 – 0.99 The correlation between actual and estimated flow is R 2 – 0.95 Normal OperationInduced Suction Condition *In-Vivo HVAD ® Pump Flow Accuracy vs. Reference Flow Probe Brown et all; ISRBP Poster #16 Istanbul, Turkey; September 2012 HeartWare HVAD ® Pump flow, when compared to reference flow probe in-vivo, proves a reliable indication of perfusion provided by the pump

16 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. VAD Flow Characteristics Rotational speed and patient state (e.g., volume or inflow position) affect VAD flow The behavior of VAD flow changes as rotational speed increases

17 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Waveform: Cardiac Cycle Flow Waveform: difference between afterload (AP) and preload (VP) Pulsatility: variation in pump flow relative to native systole and diastole As heart ejects, additional blood leaves ventricle and enters pump Despite a constant speed, pump flow increases during systole Power increases in response to increased blood volume to keep the speed at its pre-set level Increased power calculates into an increased estimated flow

18 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Waveform basics Differential Pressure (mmHg) 1800 RPM 2400 RPM 3000 RPM 3600 RPM 4000 RPM dP=60 dP=80 LVP AoP

19 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. HVAD ® Pump Waveform: Waveform Characteristics Waveform Trough Minimum value of the HVAD flow waveform Trough value should be >2 L/min and there should be >2 L/min of pulsatility Flow Pulsatility Difference between waveform maximum (peak) and minimum (trough) Dependent on heart contractility and HVAD operating points –Systole  max HVAD flow –Diastole  min HVAD flow NOTE: Flow waveforms provide additional information about the patient condition Beginning of systole Beginning of diastole Heart rate Flow Pulsatility Waveform Trough

20 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Ventricular Suction Detection A trigger value is established at 40% below the estimated flow baseline The alarm will be triggered if this condition is maintained for 10 seconds The suction alarm is cleared when the flow baseline is maintained above the trigger level for 20 seconds As the trough becomes lower, the Suction Detection Algorithm becomes more sensitive

21 CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician. Refer to the “Instructions For Use” for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events and Instructions prior to using this device. Summary of HVAD ® Pump Operation HVAD Pump is a centrifugal flow pump and is therefore preload dependent and afterload sensitive Pump speed should be set between 2400 RPM and 3200 RPM –Speeds <2400 RPM should only be used during the implant procedure when weaning from bypass –Speeds >3200 RPM are seldom needed & increase risk of suction events; pump speeds above 3200 RPM should be evaluated by ECHO Goal is to operate the pump in the normal pulsatility region –Pulsatility is affected by a number of patient conditions including left ventricular contractility, right heart function and left ventricular afterload