Stigmates IRM de l’amylose cardiaqueStigmates IRM de l’amylose cardiaque Marianna Fontana Associate Professor, Honorary Consultant Cardiologist Director of CMR UCL CMR service,

Stigmates IRM de l’amylose cardiaque Marianna Fontana

Associate Professor, Honorary Consultant Cardiologist

Director of CMR UCL CMR service, Royal Free Hospital

National Amyloidosis Centre, UCL Royal Free Hospital, London UK

Professor Sir Mark Pepys

Vendredi 23 Novembre 2018 30e Journee Internationale

du Centre Cardio-Thoracique de Monaco

Disclosure

Consultancy for GSK, Alnylam, Prothena, Ionis, Pfizer. Grant: BHF Intermediate Fellowship

Overview

� Motivation: why CMR in amyloidosis

� Existing evidence on CMR and amyloidosis

� Conclusions: where we are and future directions

1. Why we need CMR in amyloidosis

Clinical case 73 year old lady with SOB

In an adult, HCM is defined by a wall thickness ≥15 mm in one or more LV myocardial segments—as measured by any imaging technique

(echo, CMR or CT), that is not explained solely by loading conditions

HCM guidelines

Job Done!

Clinical case 73 year old lady with SOB and severe AS

Histology underlying disease processes

Hypertrophic Cardiomyopathy

Amyloidosis Leone O Amyloid 2012;19(2):99-105.

Can we get closer to histology with CMR?

Histology Underlying disease processes

2. Clinical utility: Amyloidosis

AL Amyloidosis

• Plasma cell dyscrasia > Free light chains > Amyloid • Most common type (

ATTR Amyloidosis

• Liver> Transthyretin - Wild type form - Mutant form • Exponential increase in new diagnosis

• >80 yrs 25% amyloid • Specific ethnicities

ATTR amyloidosis

Other causes of interstitial expansion: amyloid deposition

Normal Amyloid Amyloid

Maceira et al Circ 2005

Late gadolinium imaging - PSIR 3 patterns

Fontana M et al. Circulation 2015

P

Fontana M et

LGE pattern: prognosis

Fontana M et al. Circulation 2015

Need for quantitative method

track changes over time

Low eGFR

Contraindication to contrast

LGE limitations

Intrinsic contrast of the myocardium

Native T1 in AL and ATTR amyloidosis

No

Normal

No

HCM

No

AFD

No

AFD

No

AFD

Yes

Amyloid

No

Hypertension

No

AFD

Yes

AL Amyloid

No

AFD

No

AFD

No

Myocarditis

Spot the amyloid! There are 2 here

Courtesy of James Moon

2000 ms

0 ms

MOLLI at 1.5 T

� Native T1

What is T1 mapping? Native T1 and ECV

� ECV

New techniques: T1 mapping and amyloid Why should we use T1 mapping

Martinez Naharro A YIA SCMR 2017

Martinez-Naharro A et al. JACC 2017

Native T1 and ECV predict outcome

ECV and prognosis in AL and ATTR amyloidosis

Banypersad SM, Fontana M et al. EHJ 2014

ECV in ATTR amyloidosis ECV in AL amyloidosis

Normal AL amyloidosis

T2 mapping Measuring oedema

Kotecha T JACC 2018

T2 in AL and ATTR amyloidosis Disease understanding

Kotecha T JACC 2018

Kotecha T JACC 2018

T1, ECV and perfusion mapping

Martinez Naharro A YIA SCMR 2017

Mechanisms of hypoperfusion

Martinez Naharro A YIA SCMR 2017

SV x HR Low cardiac output

Concentric remodelling

Autonomic dysfunction

Microvascular dysfunction/

disruption

Electrical abnormalities

VT/VF AV conduction delays

bradycardia

Ischaemia

Ischaemia

Light Chain toxicity

Oedema

Cine T2 mapping Perfusion mapping

ECV mapping

ECGi

4. Where we are and future directions

Changing the colour of petunia

Andrew Fire and Craig Mellow Nobel prize 2006

Discovery of RNAi

Targeting amyloid deposits

Sado DM et al. Future Cardiology 20

What we want from an imaging technique: milestones

�Structure and function not enough LGE helps – but not enough Missing myocardial biology

�T1, ECV mapping ▪High diagnostic accuracy ▪Prognostic value ▪Exploratory endpoint

�T2 mapping and perfusion mapping: Changing disease understanding

�Horizon: new treatment guide treatment strategies?

[email protected]

Conclusions

Acknowledgements Acknowledgments

National Heart, Lung and Blood Institute Dr Peter Kellman Dr Hui Xue

CMR at Royal Free and National Amyloidosis Centre Dr Daniel Knight Sarah Anderson Donatella Lorusso Cassandra Zenther Dr Ana Martinez Naharro Dr Tushar Kotecha Dr Rohin Francis Dr Karl Norrington Dr Andrea Baggiano Dr Borejda Xhyheri Dr Hossam Fayed Professor Philip Hawkins Dr Julian Gillmore Dr Ashutosh Wechalekar Dr Helen Lachmann Dr Carol Whelan

CMR at the Heart Hospital/Barts Heart Centre Prof James Moon Dr Charlotte Manisty Dr Thomas Treibel Dr Sabrina Nordin Dr Anma Abdel-Gadir Dr Stefania Rosmini Dr Viviana Maestrini Dr Heerajnarain Bulluk

GOSH Dr Vivek Muthurangu

Stigmates IRM de l’amylose cardiaque Disclosure Overview1. Why we need CMR in amyloidosis Clinical case� 73 year old lady with SOBHCM guidelines Diapositive numéro 7Clinical case� 73 year old lady with SOB and severe ASDiapositive numéro 9Diapositive numéro 102. Clinical utility:Amyloidosis Diapositive numéro 12Diapositive numéro 13Other causes of interstitial expansion: amyloid depositionDiapositive numéro 15Diapositive numéro 16Diapositive numéro 17Diapositive numéro 18Diapositive numéro 19Diapositive numéro 20Diapositive numéro 21What is T1 mapping?�Native T1 and ECVDiapositive numéro 23Diapositive numéro 24Diapositive numéro 25Diapositive numéro 26Diapositive numéro 27Diapositive numéro 28Mechanisms of hypoperfusionDiapositive numéro 304. Where we are and future directions �Changing the colour of petuniaDiscovery of RNAiDiapositive numéro 34Diapositive numéro 35Diapositive numéro 36Diapositive numéro 37Acknowledgements