CMR in ACHD PH...Sex difference in mortality in PAH Jacobs, CHEST, 2014. N=101 Adjusted (height, GFR...
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CMR in ACHD PH Dr Ellen Ostenfeld Senior Consultant, PhD; ACHD, PAH, CMR; Skåne University Hospital, Lund University, Sweden. Visiting Consultant Cardiologist, Royal Brompton Hospital, London
Transcript of CMR in ACHD PH...Sex difference in mortality in PAH Jacobs, CHEST, 2014. N=101 Adjusted (height, GFR...
CMR in ACHD PH
Dr Ellen OstenfeldSenior Consultant, PhD; ACHD, PAH, CMR; Skåne University Hospital, Lund University, Sweden.
Visiting Consultant Cardiologist, Royal Brompton Hospital, London
CMR provides
• Cardiac
– RV mass volumes and function (?dilatation, hypertrophy or dysfunction)
– LV volumes (?small)
– Cardiac output
– Abnormal interventricular septal motion, TR, RA dilatation, pericardial effusion
– Myocardial morphology
– Aetiology
• Pulmonary arteries
– Size, distensibility and velocity (?stiffness ? reduced flow)
– CTEPH associated or in situ thrombus
Gold standard quantification of RV (and LV) volumes
Gold standard quantification of RV (and LV) volumes
Volumes, ejection fraction and mass derived
Multiple short axis cine slices are contoured in diastole and systole
Gold standard quantification of RV (and LV) volumes
RV and LV 3D function
• Total heart volume 800 ml
• Heart outer volume variation 60 ml
• Total heart volume variation is 8 %
Carlsson M, et al, Am J Physiol Heart Circ Physiol, 2004Carlsson M, et al, Am J Physiol, 2007: July H636-44
Longitudinal contribution to SV in PH
LVRV
LARA
Healthy control
Patient w/ PH
LV
RV
Ostenfeld E, Int J CVI, 2016.
AVPD i mm
N=17+33*** p < 0.0001
Ostenfeld E, Int J CVI, 2016.
PHpre-cap, AVPD and transplantation-free survival
Lindholm A, Poster ESC
N=86+40
Median F/U: 2.7 years
HR=2.4P=0.02
HR=3.3P<0.001
Study design
Prognostic value: ↓SVi, ↑RVEDVi & ↓LVEDVi
Van Wolferen SA et al, EHJ 2007
N=64 IPAH RHC, CMR + 6MWT
Baseline and 12 months
19 deaths
Reverse remodeling in CTEPH - before and after PEA
Reesink HJ, J Thorac CV Surg, 2007.
CTEPH: N=17
Controls:N=12
RV
LV
EDV ESV
N=100 1.9 y median FU11 deaths, 3 Tx
Van de Veerdonk MC. J Am Coll Cardiol 2011 58:2511-2519
N=110, RHC CMR 6mwt baseline and 12/12, 13 deaths 3 lung tx
PVR and RVEF for prediction of outcomes
Van de Veerdonk MC. J Am Coll Cardiol 2011 58:2511-2519
Changes in PVR or RVEF and outcome
Non significant Significant
N=110, RHC CMR 6mwt baseline and 76 had F/U exam at 12 months, 13 deaths 3 lung tx
Higher mortality in those with reduction in RVEF at 12 months
Van de Veerdonk MC. J Am Coll Cardiol 2011 58:2511-19
Sex difference in mortality in PAH
Jacobs, CHEST, 2014.
N=101
Adjusted (height, GFR and functional class) HR 7.21, p<0.001
Female
Male
• Transplantation-free survival despite equal hemodynamics• Median F/U time 5.7 years• 26 deaths and 5 lung transplants
RVEF
CMR RV changes with PAH targeted therapy
Peacock, Circ CVI, 2014.
6MWD (m) RVEF (%) SVI (ml/m2)
RVEF and LVEF and Eisenmengers outcomes
Jensen A, Broberg CS et al, Circulation; Cardiovascular Imaging 2015
N=48
Post tricuspid shunt ES
CMR and daycase
12 deaths(50% heart failure) HR 4.4 [95%CI 1.4-13.5]
Jensen A, Broberg CS et al, Circulation; Cardiovascular Imaging 2015
RVEF and LVEF and mortality in Eisenmengers
HR 6.6 [95%CI 2.1-20.8]
RV and LV EF and mortality in Eisenmengers
Jensen A, Broberg CS et al, Circulation; Cardiovascular Imaging 2015
Kaplan-Meier survival curves with the survival distributions of patients with RVEF <40% and LVEF <50% HR 8.0 [95%CI 2.5-25.1]
CMR provides
• Cardiac
– RV mass volumes and function (?dilatation, hypertrophy or dysfunction)
– LV volumes (?small)
– Cardiac output
– Abnormal interventricular septal motion, TR, RA dilatation, pericardial effusion
– Myocardial morphology
– Aetiology
• Pulmonary arteries
– Size, distensibility and velocity (?stiffness ? reduced flow)
– CTEPH associated or in situ thrombus
• Correlated with mPAP and PVRi
n=50, 6.7y (0.45-16.5), 30 IPAH, 17 CHD, 3 lung, realtime CMR, CMR augmented catheterisation
• Track acute changes in pulmonary haemodynamics using vasodilator testing
• OBS: PS or AS!!
• Significant difference in septal curvature parameters vs controls
Circ Cardiovasc Imaging. 2014
Septal curvature in PAH
Septal bowing in CTEPH - before and after PEA
Reesink HJ, J Thorac CV Surg, 2007.
N=17+12
Risk assessment in PAH
Galie, Eur Heart J, 2016.
Atrial volumes
LA
RALV
RV
AtrialVolume
Time in cardiac cycle
Max
Min
Atrial volumes and transplantion-free survival
Bredfelt et al; Accepted ESC Heart Failure, 2018
Atrial volumes and transplantation-free survival
Bredfelt et al; Accepted ESC Heart Failure, 2018
HR 1.9 (p=ns) HR 2.6 (p=0.026)
Median survival:Normal 6.2 yIncreased 3.1 y
Blyth et al., E Heart J 2005
RV-LV insertion point LGE in RVH
Septal LGE and PAH
Swift et al., JACC: Cardiovascular Imaging 2014
n=192 165 PAH
Septal LGE ---more discriminating
Only male gender independent
Broberg CS et al. Journal of Cardiovascular Magnetic Resonance 2014 16:32
Broberg CS et al. Journal of Cardiovascular Magnetic Resonance 2014 16:32
LGE findings in 30 Eisenmenger patients
LGE was common LGE did not predict clinical
outcomes
Fast gadolinium washout in presence of large intracardiac shunts
Babu-Narayan SV. The Role of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in the
Assessment of Congenital and Acquired Heart Disease. Progress in Paediatric Cardiology 2010;28:11-19
Research using better fibrosis imaging methods in larger population is ongoing
CMR provides
• Cardiac
– RV mass volumes and function (?dilatation, hypertrophy or dysfunction)
– LV volumes (?small)
– Cardiac output
– Abnormal interventricular septal motion, TR, RA dilatation, pericardial effusion
– Aetiology
• Pulmonary arteries
– Size, distensibility and velocity (?stiffness ? reduced flow)
– CTEPH associated or in situ thrombus
A B
C D
RPA
LPA
RV
LV
*
*
*
Known PH - VSD and PDA
Bradlow, Babu-Narayan and Mohiaddin, Pulmonary Hypertension in Congenital Heart Disease n Cardiac CT and MR for AdultCongenital Heart Disease. Springer 2013
• 5mm PDA• 20mm VSD • Unrestrictive
muscular VSD with right to left shunt
Known Eisenmengers
Bradlow, Babu-Narayan and Mohiaddin, Pulmonary Hypertension in Congenital Heart Disease n Cardiac CT and MR for AdultCongenital Heart Disease. Springer 2013
In situ thrombosis
• Unrestrictive VSD• Overriding aorta• Pulmonary stenosis• Dilated pulmonary arteries• In situ thrombosis
A B C
D E F
RV
RV
PAAo
RUPV
SVC
**
RA
LA RUPV
SVC
RA
PA
Ao
Pulmonary hypertension – aetiology?
Bradlow, Babu-Narayan and Mohiaddin, Pulmonary Hypertension in Congenital Heart Disease n Cardiac CT and MR for AdultCongenital Heart Disease. Springer 2013
• Dilated RV• Anomal RUPV• Sinus vensous ASD
CMR provides
• Cardiac
– RV mass volumes and function (?dilatation, hypertrophy or dysfunction)
– LV volumes (?small)
– Cardiac output
– Abnormal interventricular septal motion, TR, RA dilatation, pericardial effusion
– Myocardial morphology
– Aetiology
• Pulmonary arteries
– Size, distensibility and velocity (?stiffness ? reduced flow)
– CTEPH associated or in situ thrombus
Modulus PhaseFlow plane
Position in
oblique sagittal
(RVOT)
Flow in the pulmonary trunc
Each voxel is well delineated with a specific velocity
500 1000
0
250
500
Time (ms)F
low
ml/s
Forward flow 209 mL
Backward flow 123 mL
Stroke volume 86 mL
Regurg fraction 59 %
Pulmonary regurgitation
Normal
QP/QS=1.03
Left-to-right shunt
QP/QS=2.1
Arheden H, Stahlberg F. Blood flow measurements. In: Higgins CB,
De Roos A, eds. MRI and CT of the Cardiovascular System. Second ed.
Philadelphia: Lippincott Williams & Wilkins; 2006:71-90.
Shunt size
Bradlow. JCMR 2012;14:6
Reproduced from Kilner. JCMR 2007:9;723
CMR cannot accurately infer pressure from TR velocity
Changes with PAH
Increased afterload due to pulmonary vasoconstriction and vascular remodelling: The hemodynamic consequences of which are • Increased vascular resistance, • Reduced arterial compliance, • Elevated characteristic impedance and
abnormal wave reflections
CMR wave intensity analysis in PAH
• Non-invasively quantify reflections in the pulmonary circulation
• Differentiate between health and disease
Arterial wave reflections cause abrupt changes in vessel area and compliance which contribute to RV afterload.
Typical mid systolic notch representing early wave reflection -reduced peak velocity and earlier time to peak velocity (acceleration time)
Quail M et al, Am J Physiol Heart Circ Physiol 2015
Reiter et al,
Circ Cardiovasc Img 2008
Patient manifest PH Patient latent PH Normal
Maximal flow
Late systole
Post pulmonaryvalve closure
Utility of CMR in Pulmonary Hypertension
• Clinical use– Not (yet) the 1st-line investigation
– Awaiting robust CMR measure for assessment of PA pressure
– Accurate RV and LV volumes, mass and function / proximal PAs / Other Δ
– Especially useful in ACHD
– Prognostic data
Utility of CMR in Pulmonary Hypertension
• Clinical use– Not (yet) the 1st-line investigation
– No robust CMR measure for assessment of PA pressure
– Accurate RV and LV volumes, mass and function / proximal PAs / Other Δ
– Especially useful in ACHD
– Prognostic data
• Research– “Screen’ new drug therapies/ assess new indications prior to larger trials
– Define which CMR parameter(s) most closely linked to prognosis
– Define these in different subtypes
– Gain new pathophysiological mechanistic insights eg from 4D flow or tissue characterisation
Fellows: Riikka Rydman, StockholmBeatrice Bonello, MarseilleEe-Ling Heng, LondonVeronica Spadotto, PaduaAnnette Jensen, CopenhagenCoralie Blanche, Lausanne
CHD SurgeryDarryl ShoreBabulal SethiaAndreas HoshtitzkyGuido MichelionOlivier GhezHideki Uemura
EPSabine ErnstTom WongJan TillJulian Jarman
Physics Jenny KeeganPeter GatehousePeter Kellman, NIHMalte Roehl
CMRDudley PennellJames Moon, UCLTal Geva, BCHAnne Marie Valente, BCHGillian SmithPhilip KilnerRebecca Wassall
CHD Michael GatzoulisWei LiGerhard DillerAnselm UebingAleksander KempnyLorna SwanKostas DimopoulosSonya Babu-NarayanRafa Alonso
GeneticsStuart Cook, IC Duke NUSPaul Barton, ICLeanne Felkin, ICMiao Kui, Duke NUSSebastian Schaefer, Duke NUSEnrico Petretto, Duke NUSAida Moreno Moral, Duke NUSFrancesco Pesce, Duke NUS
Cardiac morphologyYen HoKaren McCarthyJan Lukas RobertusMary Sheppard, SGH
FellowsSarah Ghonim, LondonClaudia Montanaro, MilanIrena Ivanac, ZagrebUmberto Barbero, BolognaMaria Boutsikou, AthensEllen Ostenfeld, Lund
Imperial College LondonRoyal Brompton Hospital
Email: sonya@ imperial.ac.uk
Cardiovascular BSc studentsChristiana BoulesMarinos Ioannides
Image processingArchontis Giannakidis, NottsGuang Zhong, ICLSu Lin Lee, ICL
Inga VogesSylvia KrupickovaMichael RigbyGiovanni Di SalvoAlain Fraisse
PAHColm McCabeStephen John WortLaura Price
Lund Cardiac MR Group
Steering Committee
1. Håkan Arheden
2. Anthony Aletras
3. Marcus Carlsson
4. Henrik Engblom
5. Erik Hedström
6. Einar Heiberg
7. Ellen Ostenfeld
8. Katarina Steding-Ehrenborg
Researchers and PhD students
9. Jelena Bock
10. Helen Fransson
11. Cecilia Hindorf
12. Bo Hedén
13. Robert Jablonowski
14. Jonas Jögi
15. Mikael Kanski
16. Sascha Kopic
17. Jenny Oddstig
18. Frederik Testud
19. Johannes Töger
20. Christos Xanthis
21. Jakob Almer
22. Mariam Al-Mashat
23. Per Arvidsson
24. Jonathan Berg
25. Sebastian Bidhult
26. Petter Frieberg
27. Tom Gyllenhammar
28. Fredrik Hedeer
29. Jonas Liefke
30. Anthony Lindholm
31. David Nordlund
32. Pia Sjöberg
33. Sverrir Stephenses
34. Felicia Seemann
35. Thomas Åkesson-Lindow
Technologists
36. Ann-Helen Arvidsson
37. Christel Carlander
38. Reza Farazdaghi
39. Christel Kulberg
40. Johanna Koul
41. Lotta Åkesson
Alumni
42. Shruti Agarwal
43. Erik Bergvall
44. Peter Cain
45. Loriano Galeotti
46. Magnus Hansson
47. Karin Markenroth Bloch
48. Henrik Mosén
49. Ulrika Pahlm-Webb
50. Rainer Petzina
51. David Strauss
52. Jane Tufvesson
53. Joey FA Ubachs
54. Martin Ugander
Cardiac MR Group, Lund University
CMR in ACHD PH
Dr Ellen OstenfeldSenior Consultant, PhD; ACHD, PAH, CMR; Skåne University Hospital, Lund University, Sweden.
Visiting Consultant Cardiologist, Royal Brompton Hospital, London
