3/14/2009
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The Imaging of the RV-PA unit
Evangelos Michelakis, MD, FACC, FAHAProfessor of Medicine (Cardiology)
University of Alberta
UCSF - March 15 2009
RA
PA
A L
Nor
mal
Com
pens
atio
nF
ailu
re
Right Ventricle Pulmonary Arteries
Thin RVHealthy PA endotheliumThin walled-relaxed PAsLarge capillary network
Hypertrophied RVAbnormal PA endotheliumConstricted-stiff PAsLoss of microvessels
Dilated RVCell proliferation in the PA wallObliterative PA remodeling
Normal CONormal PVRNormal perfusion
Normal COMild increase in PVRModerate decrease in perfusion
Severe decrease in COSevere increase in PVRSevere decrease in perfusion
Circulation, 2009 - in press
“…And I ask, as the lungs are so close at hand, and in continual motion, and the vessel that supplies them is of such dimensions, what is the use or meaning of this pulse of the right ventricle? and why was nature reduced to the necessity of adding another ventricle for the sole purpose of nourishing the lungs?”
William Harvey “Exercitatio Anatomica de Motu Cordi s et Sanguinis in Animalibus”, 1628
RV LV
The RV and the LV are embryologically different
The molecular and metabolic profile of the normal RV is significantly different compared to RVH
Zaffran et al, Circ Res 2004.
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Control PAH + DCA
x40
Control
PAH
+ DCA
50
30
20
mm
Hg
0.5 sec
+DCAPAH
125x
Mitochondrial Membrane Potential
Circulation, 2002CircRes 2004Circulation 2007
DCA reverses established vascular remodeling in rat PAH
DCA
Con
trol
(n
on s
mal
l ce
ll lu
ng c
ance
r)D
CA
-tre
ated
(non
sm
all
cell
lung
can
cer)
CT scan(reconstructed tumor in blue)
PET(glucose uptake)
Mitochondrialmembrane potential
TMRM: redDAPI: blue
TMRM: redDAPI: blue Nagendran et al, JTCS, 2008
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Pressure Transducer
Inflow
Balloon
Aortic Cannula
Outflow
Silk Tie
Main PA
RV LVCoronary Sinus
Modified Langendorff isolated perfused heart
Nagendran et al, JTCS, 2008
DCA: a positive RVH inotrope
Normal RV
Pt#
1
Pt#
6
RVH
SMA
MHC
40X
PDE5
PDE5
SMA+PDE5+DAPI
MHC+PDE5+DAPI
Pt#
5
Pt#
7
SMA
PDE5
PDE5
MHC MHC+PDE5+DAPI
SMA+PDE5+DAPI
Nagendran et al, Circulation 2008
10 m
mH
g10
mm
Hg
1 min
1 min
0.1 sec
baseline MY-5445 10-6M
0.1 sec
10 m
mH
g10
mm
Hg
MY-5445 10-6M
Sildenafil: a positive RV inotrope in RVH
nRV
RVH
-400
-300
-200
-100
0
100
200
300
400
-400
-300
-200
-100
0
100
200
300
400
dP/d
t (m
mH
g/se
c)
1st derivative
Nagendran et al, Circulation 2008
sildenafilsildenafil
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PDE5A Inhibitor Treatment of Persistent Pulmonary HypertensionAfter Mechanical Circulatory Support
Tedford et al, Circulation: Heart Failure, Nov 2008
Sildenafil improves RV contractility in patients with persistent PAH post LVAD
ETR-A is up-regulated in Human RVH
RVH
nRV
ETR-A MHC Merge
MHC MergeETR-A
ET-1 is expressed in Human RVH
MHC Merge
MHC Merge
ET-1
ET-1
The ET axis is up-regulated in human RVH(representative of 16 patients)
ET-A receptor(48 kDa)
RV RVH
GAPDH
RV RVH
GAPDH
Endothelin-1(24 kDa)
10 min
20
40
0
Endothelin Receptor Antagonists Decrease Contractility in RVH
Bosentan 10-6M
Sildenafil 10-6M
Krebs Krebs
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0
20
40
60
80
100
120
ECHO RVSP
0 100 200 300 400 500 600
6 min walk
0
20
40
60
80
100
120
140
PAAT
0 100 200 300 400 500 600
6 min walk
LV endocardialcontour
LV epicardial contourRV epicardial contour
RV endocardialcontour
0
100
200
300
400
500
600
0 100 200 300 400 500 600 700
PVRi
P<0.02
dynes.sec/cm5.m2 100
200
300
400
500
600
6 min walk
20 40 60 80 100 120
rv mass/bsa
P<0.001
gm/m2
van Wolferen, S. A. et al. Eur Heart J 2007 28:1250 -1257.
Prognostic Significance ofCMR Derived RV Measures
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Interstudy Reproducibility of CMR
Grothues F et al AHJ 2004
N=60Mean Difference
±±±± SD
Coefficient of Variability
(%)
RVEDVi (ml/m2) 0.9 ± 4.7 6.2
RVSVi (ml/m2) 0.6 ± 6.7 8.2
RVEF (%) -0.1 ± 4.9 8.3
RV mass i (g/m2) -0.2 ± 2.9 8.7
Advantage of True Volumes
Adapted from Strohm et al. JMRI 2001.
LV Mass Method Sample Size to Detect a 10% Difference
P value
2-D Echo Teicholz 2443
2-D Echo Biplanar 898 <0.01
CMR 35 <0.001
LA
LV
AoRV
Measuring Cardiac Output with MRI
3 Chamber View
Perpendicular imaging plane is prescribed to capture the vessel cross-section
Aortic Valve Plane (Magnitude)
Aortic Valve Plane (Velocity)
PA Stiffness
Diastole Systole
Gan et al. Chest 2007;132:1906-12.
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PA Stiffness
Gan et al. Chest 2007;132:1906-12.
RV Pressure Volume Loops
MRI
CathPH vs control
Kuehne et al. Circulation 2004;110:2010-16.
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RA
PA
Severe PAH Moderate PAH
Normal
A 54 year old man with hemophilia and HIV-induced PAH. He presented with a rapidly worsening CHF and was found
to have PA pressure of 100/45 with a PAWP of 9 mmHg.
RA
PA
MR Perfusion ImageMR Angiogram Low FlowRegion
High FlowRegion
Ohno, Y. et al. Am. J. Roentgenol. 2007;188:48-56
NORMAL PPH
Lung Perfusion:CMR Derived Peak Blood Flow
Ohno, Y. et al. Am. J. Roentgenol. 2007;188:48-56
r = -0.79
PBF Correlation with Cath
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Contrast Time Intensity Curves1 2 3 4 5MRA – Coronal MIP
Upper Right LungNo Visible Arteries
?
Right Lung (slice 2) Left Lung (Slice 4)
Time 1(35 seconds)
1 2 3 4 5
?
MRI Lung Perfusion: Pre-Thromboarterectomy (Dec 02, 2008) 1 2 3
4 5
Slice Orientation
Summary: Upper right lung and middle left lung near the chest have a significant delay in the onset of contrast arrival – left lung region also have reduced upslope and peak value (i.e. significantly reduced perfusion). Note the delay in the green curve on the left figure and the red curve in the right hand figure.
Dr. Richard Thompson, Department of Biomedical Engineering
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1 2 3 4 5MRA – Coronal MIP
Upper Right LungVessels Now Visible
1 2 34 5
Slice Orientation
MRI Lung Perfusion: Post-Thromboarterectomy (Dec 19, 2008)
Time 1(35 seconds)
1 2 3 4 5
Contrast Time Intensity CurvesRight Lung (slice 2) Left Lung (Slice 4)
Dr. Richard Thompson, Department of Biomedical Engineering
Summary: All contrast arrival delays were corrected by surgery. Left lung now has uniform and good perfusion. Lower chest on right lung now has a new significant flow abnormality (red curve on left figure directly above). Note the arterial input function is sharper than pre surgery - may imply that impedance is reduced.
1 2 34 5
Slice Orientation
MRI Lung Perfusion: Post-Thromboarterectomy (March 11/09)
Time 1(35 seconds)
1 2 3 4 5
Pre- Post-
CMR Cost
Picano E. Cardiovasc Ultrasound 2005
Unit Cost
Echocardiography 1
CT 3.1
SPECT 3.27
CMR 5.51
PET 14.03
Cardiac cath 19.96 MRI PET
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Before AfterTherapy with Flolan decreases RV glucose uptake
Increased lung glucose uptake in iPAH patients
RV
LV
RV
LV
Increased RV glucose uptake in iPAH
Oikawa et al, JACC 2005
Xu et al, PNAS, 2007
Thank youStephen Archer, MDLinda Webster, NPSebastien Bonnet, PhDSean McMurtry, MD, PhDJayan Nagendran, MDGopi Sutendra, MScAl Haromy, BScSandra Bonnet, MScKyoko Hashimoto, BSc
Richard Thompson, PhDIan Paterson, MD
Ballarina II, Joan Miro, 1925