Dr. Dan Burkhoff joined InsideScientific for Part two of "Basic Hemodynamic Principles Viewed Through Pressure-Volume Relations". In this session, advanced PV Analysis concepts were discussed, along with best-practices during data acquisition and statistical analysis. An extended Q&A session includes detailed answers on subjects from seminar 1. Session 1: The goal of this webinar was to provide an overview of the fundamental principles of preload, afterload, contractility and lusitropy (diastolic properties), how these are quantified on the pressure-volume diagram, and how they are affected in heart failure. Measurement techniques were reviewed. Links were made to underlying properties of cardiac muscle and ventricular structure. After establishing basic concepts, it was demonstrated how pressure-volume analysis can lead to a quantitative understanding of how heart and vasculature interact to determine stroke volume, cardiac output and blood pressure. The implications for understanding therapeutic effects were also discussed. Key Concepts: - Preload, Afterload, Contractility and Lusitropy - Cardiac Muscle and Ventricular Structure - Understanding Heart-Vasculature Interactions - PV Loops in Heart Failure - Understanding Therapies and Their Effects on Cardiac Pump Performance

1. 1

2. Advanced Concepts in
Pressure-Volume Analysis
Daniel Burkhoff MD PhD
Adjunct Associate Professor
Columbia University

3. 3
If your research involves studying the effects of altered
genes, cells, extracellular matrix, drugs, etc, on
cardiovascular properties, there are several key
concepts, indexes and measurement techniques you
should be aware of:
PRELOAD
AFTERLOAD
CONTRACTILITY
LUSITROPY

4. 4
Resources
Harvi
Interactive, simulation-based textbook for
the iPad
iPad 2, 3 and mini (iOS 6)

5. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
MV Closes
AoV Opens
AoV
Closes
MV
Opens
Isovolumic
Contraction
Isovolumic
Relaxation
Filling
Ejection
The Cardiac Cycle
Pressures-Volumes Loop
5

6. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
6
Pressure-Volume Loops and Relationships

7. 7
EDPVR and ESPVR define the boundaries within
which the PV Loop sits, independent
of “preload” and “afterload”

8. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
Vo
Ees
End-Systolic Pressure-Volume
Relationship
(ESPVR)
Pes = Ees(Ves-Vo)
8
End-Systolic Pressure-Volume Relationship

9. 9
Contractility:
The concept applied to the Left Ventricle

10. 0 50 100 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
Ees
Ees
10
Contractility

11. 0 75 150
0
LV Volume (ml)
LVPressure
(mmHg)
10
20
30
End-Diastolic Pressure-Volume Relationship
11
Vo
P = β(eα(V-Vo)-1)

12. 12
Lusitropy:
Passive Diastolic Properties

13. 0 125 250
0
LV Volume (ml)
LVPressure
(mmHg)
10
20
30
Diastolic Capacitance
= volume at a given pressure
13
Lusitropy:
Passive Diastolic Properties

14. 14
ESPVR:
Advanced Concepts

15. 15
ESPVR:
Advanced Concepts

16. 16
ESPVR:
Advanced Concepts

17. 17
Possible ESPVR Changes in Response to Intervention

18. 18
ESPVR:
Practical Recommendations
• Linear regression over the range of available data
• Report both Ees and Vo
• Use Analysis of Covariance (or multiple linear
regression analysis with dummy variables) to
compare ESPVRs measured under different
conditions
• Do not use t-tests compare slopes or Vo values
• An alternative is to use volume and a specified
pressure (e.g., V120)

19. 19
EDPVR:
Advanced Concepts

20. 20
EDPVR:
Advanced Concepts
P=βVα
P= β(eα(V-Vo)-1)

21. 21
EDPVR:
Advanced Concepts
EDPVR can be linearized by
logarithmic transformation:
P=βVα
Ln(P) = Ln(β) + αLn(V)
As for ESPVR:
• Report both values of α and β
• Use analysis of covariance to
assess for shifts of EDPVR
0
10
20
30
40
50
0 50 100 150 200
y = 4x - 7
-5
-4
-3
-2
-1
0
1
2
0.5 1 1.5 2 2.5
Pressure-Volume
Ln(P) – Ln(V)

22. 22
EDPVR: Alternative Analsyis
V30

23. Questions

24. Physiology & Hemodynamic Concepts
• What is the importance of Tau?
• What conformational changes occur in a PV loop plot,
other than a rightward shift of the PV-loops, that
confirm the subject has heart failure?
• What is Arterio-Ventricular Coupling?
24

25. 0 50 100 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
EDV
SV
Pes  MAP
25
Ventricular-Vascular Coupling on the PV Diagram

26. Physiology & Hemodynamic Concepts
• In HF do PV loops maintain their classical shape? In this
case, are there changes to the way hemodynamics are
calculated (ie. SV, SW, CO)?
• What is the effect of heart valve disorders on PV Loops
(aortic stenosis and mitral valve incompetence)?
• Besides differences in pressure, how would RV PV
loops differ from LV PV loops?
26

27. 27
ESPVR in CHF

28. 28
PV Loops in Valve Lesions
Normal AS MR

29. 29
RV vs LV PV Loops

30. Methodology & Best-Practices
• How can PV loops be used to assess the cardiac safety
of new drugs? Do you see this as a requirement?
• How many PV loops should be included for occlusion
data measurements?
• Are there special considerations for PV loop
measurements in isolated working heart models?
30

31. Load-Independent Measurements
• Strain rates and related analyses have been suggested
as a load-independent means of measuring myocardial
function and can be looked at globally to assess
ventricular function in-vivo with techniques like
speckle tracking. Can you comment on this and your
opinion regarding myocardial strain analysis as a
practical, load-independent measure of cardiac
function?
31

32. Load-Independent Measurements
• Work by Glower et al indicated the end-systolic
pressure volume relationship was relatively load and
heart rate independent within a defined physiologic
range. What afterload and heart rate ranges do you
feel pressure-volume loop relationships are most
appropriately utilized?
32

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protocols, research tools and laboratory services.

35. Thank you for taking part in this event.We encourage all attendees to
register at www.insidescientific.com for notifications about future webinars.
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Wednesday, April 9th @ 11AM EST
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