Current risk stratification in ARVC - Heart Rhythm Congress€¦ · Current risk stratification in...
Transcript of 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
ARVC
Risk stratification in ARVC
Reliable risk factors
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
Risk stratification in ARVC
Reliable risk factors
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
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?
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
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
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
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
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
Appropriate ICD therapy
- - - 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
Appropriate ICD therapy
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
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
Appropriate ICD therapy
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 Appropriate ICD Therapy
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?
Corrado Circ 2003;108:3084
Actual survival versus freedom from VF/VFL
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
Appropriate ICD therapy
16.2 10.2 6.8
LAE 8.0 6.0 2.2
Sudden death 0.8 0.3 0
ICD Cohorts – Life Threatening Arrhythmic Events
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
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
Appropriate ICD therapy
- 6
LAE 1.6 -
Sudden death 0.4 0
Natural history cohorts – relatives
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?
Cohort Italian / US
Italian John Hopkins
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
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?
Cohort Italian / US
Italian John Hopkins
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
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?
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