Forward Looking Statement

Transcription

1 Forward Looking Statement This presentation contains forward-looking statements. All forward looking statements are management s (Dave Rosa) present expectations of future events and are subject to a number of risks and uncertainties. Various factors (collecting more data) could cause actual results to differ materially from these statements...

2 Hemodynamics of C-Pulse: Kangaroos, Waves and Reflexes FRM C

3 Simple Model of Cardiovascular System 1

4 Principles of Counterpulsation Reduce Afterload Augment Diastolic Pressure Increase Coronary Perfusion Secondary pulsatile heart 2

5 Counterpulsation Mechanism Based On Physiologic Hemodynamics of Wave Reflections McDonald s Blood Flow In Arteries. 6th Ed. Supports the failing heart it is not a flow source. It optimizes hemodynamic conditions for ventricular ejection and myocardial perfusion. GOAL: Stabilize/reverse myocardial function and re-sensitize system to HF meds 3

6 The Aorta 4

7 Ascending Aorta: Key Predictor of Outcomes Passive Wrap 5

8 C-Pulse Design: Unique Placement on Ascending Aorta Proximal Aorta 70% of compliance in Arterial System PROXIMITY TO AORTIC VALVE AND UNIDIRECTIONALITY AS PRIME FACTORS IN COUNTERPULSATION EFFECTIVENESS S. Furman, R Whitman, J. Stewar, B. Parker, and M. McMullen An aortic occlusive balloon of small volume distal to the volume displacing balloon projected virtually the total displacement toward the heart and increased arch and coronary blood flow. Vol. XVII Trans. Amer. Soc. Artif. Int. Organs 6

9 C-Pulse Counterpulsation: Clinical Examples Video 1 Video 2 Videos seen in presentation online courtesy of Dr. Daniel Bujnoch; Department of Cardiac Surgery, University of Erlangen, Germany 7

10 Right Heart Catheterization 4-Months Parameter OFF ON Heart Rate (bpm) (Paced) PA Pressure (Systolic/Diastolic) mmhg /25 51/19 CVP (mmhg) 6 5 PCWP (mmhg) Cardiac Output (L/min) Thermodilution O 2 Saturation (%)

11 Effects of Increased Load on Left Ventricle Wasted energy (W E ) and Tension-Time Index (TTI), Augmentation Index (Aix) are elevated in HF Aix=P s - P i /P s -P d A Key determinants of myocardial oxygen consumption Reduce stroke volume Increase wall stress Diastolic dysfunction 9

12 Pulsatile Load Increased in CHF Mitchell GF. Clinical AcheivementsImpedance Analysis. Med.Biol. Eng. Comput 2008 Milnor, WR. Arterial Afterload. In Busse; Arterial System

13 Central Hemodynamics and C-Pulse OFF OFF ON ON 11

14 Hemodynamic Effects of Unloading with C-Pulse C-Pulse OFF C-Pulse ON 12

15 Wall Stress and Shortening Velocity 13

16 C-Pulse Reduces Wall Stress and Increases Shortening Velocity Leggett et al. 112:I

17 Myocardial Oxygen Consumption (MVO 2 ) The heart is especially vulnerable to ischemia, because its O2 extraction ratio is 65% (vs. average of 25% for rest of body) Because the heart is near maximal O 2 extraction more O 2 during increased demand, primarily accomplished by increasing blood flow Myocardial wall stress best correlate of MVO 2 15

18 Boost Diastolic Pressure: Reservoir for Coronaries to Fill OFF OFF ON ON 16

19 Coronary Flow (ml/min) C-Pulse Effect on Coronary Hemodynamics in Normal Swine 250 OFF 200 C-Pulse Backward waves from descending less efficiently propagated to aortic root Time Mynard et al. J. Hypten. 33:

20 Wave Intensity Analysis of Coronary Flow: Reservoir for Coronary Suction from the Aorta Davies et al. Circ. 113:

21 Ejection Fraction (%) End Systolic Volume (ml) Cardiac Function in OPTIONS HF Ejection Fraction End Systolic Volume Baseline Month 6 Baseline N=11 N=8 N=11 N=8 0 Month 6 19

22 Feasibility Study: Improved Filling Pressures and Diastolic Function No N=13 Sunshine Heart data on file 20

23 Rat Heart Courtesy of: Dr. Frits Meijler CAUTION: C-Pulse is an Investigational device. The device is limited by Federal (or United States) Law to Investigational use only. 21

24 Counterpulsation Timed to Most Sensitive Phases of Cardiac Cycle for Baroreceptor Stimulation Central Aortic Pressure Arterial Baroreceptor Activity Peterson, LH. Circ. 21:

25 Large Unloading Effects Partly Due to Neural Reflexes from the Aortic Arch? American Journal of Physiology Vol. 221, No. 3, September Printed in U.S.A. Direct and reflex vascular effects of intra-aortic balloon counterpulsation in dogs C-Pulse balloon placement even more optimal location to activate reflexes Mitchell GAG. Anatomy Autonomic Nervous System

26 Sympathetic Outflow from the Brain Beta Blockers Diuretics ACE/ARB Heart Failure: Companion to Braunwald s Heart Disease. 3 rd Edition. D.L. Mann and G. M. Felker Nitrates Vasodilators ACE/ARB 24

27 Cardiac Output Regulated by the Circuit REGULATION OF CARDIAC OUTPUT Arthur C. Guyton, M.D. Jackson, Mississippi MOST physicians are surprised to learn that the heart has relatively little effect on the normal regulation of cardiac output, but all the physician has to do is to look Clin Chest Med May;4(2): The role of the vasculature in the regulation of cardiac output. Sylvester JT, Goldberg HS, Permutt S. at his patients, and he will see NEJM: It is axiomatic that the heart can pump as much blood as it receives. Carl Wiggers 25

28 Systemic Effects of Sympathetic Activation F Afterload Black, HR. Braunwald s Hypertension;

29 Technique to Measure Sympathetic Nerve Activity 27

30 Pulsatility and Sympathetic Nervous System Individual and mean muscle sympathetic nerve activity (MSNA) burst frequencies in healthy controls and patients with pulsatile and nonpulsatile left ventricular assist devices in the supine position and during upright tilt. Markham D W et al. Circ Heart Fail. 2013;6: Copyright American Heart Association, Inc. All rights reserved. 28

31 LVADs Do Not Normalize Circulation or Regulation of Cardiac Output Brasard et al. Circ. Heart. Fail. 4: Cornwell et al. ISHLT

32 Arterial Baroreceptor Denervation and Volume Management Control MAP 103.9±5.8 SAD MAP 104.7±6.1 SD of AP SD of LAP Period of high LAP (>18mmHg) (mmhg) (mmhg) (sec) SAD ( - ) ( + ) SAD ( - ) ( + ) SAD ( - ) ( + ) Fig. 1: Sinoaortic denervation (SAD) induces the increase of SD in AP and LAP, and the elevation of LAP. Funakoshi K et al. J.Card. Fail. 20(1);

33 C-Pulse and Volume Management C-Pulse Therapy Patient with Cardiomems C-Pulse OFF Submitted to HFSA

34 Renal Artery Flow (ml/min) C-Pulse Effects on Renal Blood Flow Normal Swine 250 Diastolic Augmentation ON OFF Time 32

35 Baroreceptor Stimulation Effects on Renal Artery Flow Bazzato et. al. Minerva Nefrologica. XIII Congresso Nazionlae 33

36 C-Pulse Therapy Goal Hit the vicious cycle! Supports the failing heart it is not a flow source. It optimizes hemodynamic conditions for ventricular ejection and myocardial perfusion. GOAL: Stabilize myocardial function and circulatory homeostasis and re-sensitize system to HF meds 34

37 Pressure-dimension Loops Before (Control) and After Milrinone (Mil) Increase in Cardiac Output only at expense of increases MVO2 Hideaki Senzaki et al. Circulation. 2000;101:

38 Thank you!