current risk stratification in arvc - heart rhythm congress€¦ · current risk stratification in...

Current risk stratification in ARVC

Dr Stephen PageConsultant Cardiologist & ElectrophysiologistInherited Cardiovascular Conditions Service

Leeds General Infirmary

Heart Rhythm Congress8th October 2018

Risk stratification in ARVC

Reliable risk factors



Difficult to define

46 yo man

Echo: dyskinesia and dilated RV

2 major, 2 minor

Fulfills 2010 TFC for ARVC

Classic ARVC

23 yo man

Echo: global hypokinesia

1 major, 1 minor

Borderline 2010 TFC for ARVC

Probable ARVC

19 yo woman

PKP2 mutation carrier

Asymptomatic

SAECG - +ve 3 vectors

Imaging – minor criterion

Fulfills 2010 TFC for ARVC in a relative

Familial ARVC



Difficult to defineSD first presentationConcealed phaseProgressive disease

Rare – data lackingAscertainment biasSD first presentation

Which end-point?Heterogeneous cohorts

What are the outcomes in ARVC?

1. What is the risk of sudden death?

2. What is the risk of life-threatening arrhythmias?

3. What are the risks of complications from ICD therapy?

4. What is the risk of inappropriate therapy?

0 50 100 150 200 250 300 350

Italian 2003

German 2004

Canada 2016

John Hopkins 2017

Italian 2017

Dutch 2017

Norway 2017

NIH 2009

ARVC Registries

0 500 1000 1500 2000 2500 3000 3500

ESC HCM risk cohort

Italian 2003

German 2004

Canada 2016

John Hopkins 2017

Italian 2017

Dutch 2017

Norway 2017

NIH 2009

ARVC Registries in Context

Cohort French Italian(Trieste)

Italian John Hopkins / Dutch

Norwegian

Year 2003 2011 2017 2017 2018

n 130 96 267 439 117

Probands % 100 79 53 100 29

Follow up 8.1 10 5.8 7.0 2

ICD % 8 16 27 84 18

Previous VA 79 - 0 65 0

Appropriate ICD therapy

- - - 10.3 6

LAE - - 3.0 - -

Sudden death 0.7 0.6 0.7 0.4 (2.3) 0

Natural history cohorts – risk of sudden death

Cohort French Italian(Trieste)

Italian John Hopkins / Dutch

Norwegian

Year 2003 2011 2017 2017 2018

n 130 96 267 439 117

Probands % 100 79 53 100 29

Follow up 8.1 10 5.8 7.0 2

ICD % 8 16 27 84 18

Previous VA 79 - 0 65 0


- - - 10.3 6

LAE - - 3.0 - -

Sudden death 0.7 0.6 0.7 0.4 (2.3) 0

NIH/DutchItalian

French

2016 2018

88 137

100 -

9.1 3.5

0 0

18 -

- -

- -

0.6 1.0

Natural history cohorts with no ICD – risk of sudden death

Cohort Italian / US German John Hopkins

Year 2003 2004 2017

n 132 60 312

Probands % 100 100 81

Follow up 3.3 6.7 8.8

ICD % 100 100 100

Previous VA 72 93 57


16.2 10.2 6.8

LAE 8.0 6.0 2.2

Sudden death 0.8 0.3 0

Italian John Hopkins

2010 2016

106 84

100 83

4.8 4.7

100 100

0 0

4.1 10.2

3.3 2.4

0 0

Primary preventionPrimary and Secondary prevention

ICD Cohorts – Risk of Sudden Death


Year 2003 2004 2017

n 132 60 312

Probands % 100 100 81

Follow up 3.3 6.7 8.8

ICD % 100 100 100



16.2 10.2 6.8

LAE 8.0 6.0 2.2



2010 2016

106 84

100 83

4.8 4.7

100 100

0 0

4.1 10.2

3.3 2.4

0 0


ICD Cohorts – Risk of Appropriate ICD Therapy






Corrado Circ 2003;108:3084

Actual survival versus freedom from VF/VFL


Year 2003 2004 2017

n 132 60 312

Probands % 100 100 81

Follow up 3.3 6.7 8.8

ICD % 100 100 100



16.2 10.2 6.8

LAE 8.0 6.0 2.2


ICD Cohorts – Life Threatening Arrhythmic Events


2010 2016

106 84

100 83

4.8 4.7

100 100

0 0

4.1 10.2

3.3 2.4

0 0


Cohort John Hopkins / Dutch Norwegian

Year 2017 2018

n 562 117

Probands % 0 29

Follow up 5.0 2

ICD % 18 18

Previous VA 0 0


- 6

LAE 1.6 -

Sudden death 0.4 0

Natural history cohorts – relatives






Cohort Italian / US


Year 2003 2010 2017

n 132 106 312

Follow up 3.3 4.8 8.8

Complications 4.7 3.5 2.4

Inappropriate therapy

5.3 4.0 2.4






1-2% per year without an ICD0-0.5% per year with an ICD

2-8% per year2-3% per year if no previous VA

5 % per year

5 % per year

0.4%

0.6%

HCM

Risk factors for cardiac death or ICD therapy

ARVC

Ventricular arrhythmias

• Cardiac arrest• Sustained VT• NSVT

Symptoms

• Syncope • Heart failure

Imaging

• LV dysfunction• RV dysfunction• BiV dysfunction• RV/RA dilatation

Demographic

• Young age• Male gender• Complex genetic status• Proband status• Excessive exercise

EP study

• Inducible VT/VF• Extensive endo scar• Fragmented EGMs

ECG • Inf TWI• Extensive TWI• QRS fragmentation• Precordial QRS amp ratio

Paper Task Force Consensus

Large Registry Review article Meta-analysis

Year 2015 2017 2017 2018

Previous VT

PVCs > 1000

NSVT

+ EPS

Young age at presentation

Syncope

Male gender

RVSD

LVSD

TWI

Proband status

Multiple mutations

Strenuous exercise

Moving Goalposts

Risk factors for cardiac death or ICD therapy

ARVC

Ventricular arrhythmias

• Cardiac arrest• Sustained VT• NSVT

Symptoms

• Syncope • Heart failure

Imaging

• LV dysfunction• RV dysfunction• BiV dysfunction• RV/RA dilatation

Demographic

• Young age• Male gender• Complex genetic status• Proband status• Excessive exercise

EP study

• Inducible VT/VF• Extensive endo scar• Fragmented EGMs

ECG • Inf TWI• Extensive TWI• QRS fragmentation• Precordial QRS amp ratio

High Risk Intermediate Risk Low Risk

Risk Assessment in ARVCTask Force Consensus

(life threatening arrhythmic events)

Cardiac arrest survivorsSustained VTSevere LV/RV dysfunction

Major- Syncope- NSVT- Mod LV/RV dysfunction

Minor- ≥ minor RF

No risk factorsHealthy gene carriers

ICD (I)Risk > 10%

ICD (IIa/IIb)Risk 1-10%

No ICDRisk < 1%

e.g. genotype, proband status, Males, young age, ECG criteria etc

Corrado Circ 2015;132:441

Recommendation Risk Factor

I VF or haemodynamically unstable VT

IIa Haemodynamically stable VT

IIb 1 or more “RFs”

ESC GUIDELINES

2015 ESC Guidelines for the management

of pat ients with ventr icular arrhythmias

and the prevention of sudden cardiac death

The Task Force for the Management of Pat ients with Vent r icular

Arrhythmias and the Prevent ion of Sudden Cardiac Death of the

European Society of Cardiology (ESC)

Endorsed by: Associat ion for European Paediat r ic and Congenital

Cardiology (AEPC)

Authors/Task Force Members: Silvia G. Pr ior i* (Chairperson) (Italy),

Car ina Blomstr om-Lundqvist * (Co-chairperson) (Sweden), Andrea Mazzant i† (Italy),

N ico Blom a (The Nether lands), Mart in Borggrefe (Germany), John Camm (UK),

Perry Mark Elliot t (UK), Donna Fitzsimons (UK), Robert Hatala (Slovakia),

Gerhard Hindr icks (Germany), Paulus Kirchhof (UK/Germany), Keld Kjeldsen

(Denmark), Kar l-Heinz Kuck (Germany), Antonio Hernandez-Madr id (Spain),

N ikolaos Nikolaou (Greece), Tone M. Norekval (Norway), Chr ist ian Spaulding

(France), and Dirk J. Van Veldhuisen (The Nether lands)

* Corresponding authors: Silvia Giuliana Priori, Department of Molecular Medicine University of Pavia, Cardiology & Molecular Cardiology, IRCCSFondazione Salvatore Maugeri,

Via Salvatore Maugeri 10/10A, IT-27100 Pavia, Italy, Tel: + 39 0382 592 040, Fax: + 39 0382 592 059, Email: [email protected]

CarinaBlomstrom-Lundqvist, Department of Cardiology, Institution of Medical Science, UppsalaUniversity, SE-751 85 Uppsala, Sweden, Tel: + 46 18 611 3113, Fax: + 46 18 510 243,

Email: [email protected] the Association for European Paediatric and Congenital Cardiology (AEPC).

†Andrea Mazzanti: Coordinator, affiliation listed in the Appendix.

ESC Commit tee for Pract ice Guidelines (CPG) and Nat ional Cardiac Societ ies document reviewers: listed in the Appendix.

ESC ent it ies having part icipated in the development of this document:

ESC Associat ions:AcuteCardiovascular CareAssociation (ACCA),European Association of Cardiovascular Imaging(EACVI),European Association of PercutaneousCardiovascular

Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA).

ESC Councils: Council for Cardiology Pract ice (CCP), Council on Cardiovascular Nursing and Allied Professions (CCNAP), Council on Cardiovascular Primary Care (CCPC),

Council on Hypertension.

ESC W or king Groups: Cardiac Cellular Electrophysiology, Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Grown-up Congenital Heart Disease, Myocardial and

Pericardial Diseases, Pulmonary Circulation and Right Ventricular Function, Thrombosis, Valvular Heart Disease.

Thecontent of these European Society of Cardiology (ESC) Guidelines hasbeen published for personal and educational use only.No commercial use isauthorized.No part of theESC

Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford

University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC.

Disclaimer: The ESC Guidelines represent the viewsof the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at

the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recom-

mendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encour-

aged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or

therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and

accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor

do theESC Guidelines exempt health professionals from takinginto full and careful consideration the relevant official updated recommendations or guidelines issued by the competent

public health authorities, in order to manage each patient’s case in light of the scientifically accepted datapursuant to their respective ethical and professional obligations. It isalso the

health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

& The European Society of Cardiology and the European Respiratory Society 2015. All rights reserved. For permissions please email: [email protected].

European Heart Journal

doi:10.1093/eurheartj/ehv316

European Heart Journal Advance Access published August 29, 2015

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Priori EHJ 2015;36:2793

Meta-analysis of risk stratification in ARVC

Bosman Heart Rhythm 2018;15:1097

Practical approach to risk stratification

PROBANDWITH VA

RECOMMEND AN ICD

PROBANDWITHOUT VA

DISCUSS ICD CONSIDERING RFs

(LVSD/RVSD, symptoms, NSVT, genotype, age,

ECG criteria etc) versusRISKS

RELATIVECLEAR DISEASE

EXPRESSIONDISCUSS ICD

CONSIDERING RFs(LVSD/RVSD, symptoms,

NSVT, genotype, age, ECG criteria etc)

versusRISKS

RELATIVEWITH BORDERLINE

PHENOTYPE OR G+P-

ICD NOT INDICATED

Conclusions

• Our ability to risk stratify patients is limited

• Ventricular arrhythmias are common, but not necessarily life-threatening

• ICD therapy is a major part of management

Leeds Regional Inherited Cardiovascular Conditions Service

Stephen Page Consultant Cardiologist & ElectrophysiologistAlex Simms Consultant CardiologistWaz Baig Consultant Cardiologist (Aortopathy)Rob Sapsford Consultant Cardiologist (Neuromuscular)Annabel Nixon ICC Specialist NurseClare Taylor ICC Specialist NurseGemma Bassindale Adult EchocardiographerCraig Russell Specialist nurse ICD therapy, Ajmaline testing

Ros Jewell Consultant GeneticistJenny Thomson Consultant GeneticistKatrina Prescott Consultant GeneticistJude Edhouse Genetics CounsellorKath Ashcroft Genetics CounsellorIan Berry Clinical Scientist

Elspeth Brown Consultant Paediatric CardiologistJan Forster Paediatric Echocardiographer

Jayne Slack Senior Counsellor

Lisa Barker Consultant PathologistMark Busby Consultant Neurologist

Lyn McGovern Clerical

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