Lesion-specific Risk Stratification of

Sudden Cardiac Death and Ventricular Arrhythmias

in Adults with Congenital Heart Disease.

How to predict it?

Pastora Gallego, MD, PhDIntercenter Adult Congenital Heart Disease

Hospital Universitario Virgen del Rocio

Sevilla, Spain

On behalf of the Spanish ACHD Network Investigators

No conflict of interest to

disclose

European Heart Journal 2017

3311 consecutive ACHD FU 37608 person-years336 deathsAnnual Death Rate 0.89%

MODE OF DEATH

Sudden Cardiac Death is the leading mode of death at young age

incidence of sudden cardiac death in

adult congenital heart disease

Author Year PatientsFollow-up

person-years SCDAnnual Rate of

SCD

Silka 1998 3589 45857 41 0.089

Zomer 2012 8595 26500 51 0.192

Diller 2015 6969 70967 37 0.052

Engenligs 2016 2596 14114 55 0.389

Moore 2017 2935 85276 35 0.041

Oliver 2017 3331 37608 56 0.149

Total 28015 280322 275 0.098

sudden cardiac death and complexity

of underlying heart defect

Incidence of late SCD Simple CHD

0.04 / 1000 patient-years(1/25,000 patient-years)

Moderate CHD0.57 / 1000 patient-years(1/1,754 patient-years)

Severe CHD2.00/ 1000 patient-years

(1/500 patient-years)

Moore B. Int J Cardiol 2018 2935 CHD patients

Aged > 16 years old

35 cases of SCD

19%

19%

16%13%

11%

11%

4%

3.5% 3.5%

Eisenmenger

TGA (cc)

Fallot

LVOT lesions

Septal defects

Cianotic CHD

Fontan

Ebstein

Other

Distribution of SUDDen cardiac deaths by defect

Koyak Z. Circulation 2012

CLINICAL STUDYMultinational Case-Control Study

Surgical FU & Natural History of Inoperable Cases

N = 171 cases of presumed arrhythmic deaths

Sudden Cardiac Arrest

N=22SCD

n = 15

Resuscitated Cardiac Arrest

n = 5

Appropriate Shock

n = 2

Incidence

(2.6/1000 pts-year)10

1.2

3.7

2.11.4

0

3

6

9

12

TGA UVH CoAo Fallot Others

CHD TypesPrevalence and incidence were estimated for overall populationand for each diagnostic category.

Gallego P. Am J Cardiol 2012

POSTOPERATIVE ACHD POPULATION

936 postoperative ACHD patients

FU 8387 person-years

Systemic ventricular dysfunction

and Sudden cardiac arrest

Systemic VentricleFunction

SSVD(n=69)

Non-SSVD(n=867)

p

SCD(n & %) 16 (23%) 6 (0.7%) <0.001

All-cause death or TX(n & %) 28 (41%) 22 (2.5%) <0.001

SCD/All-cause death or TX Ratio

57% 27% <0.001

TX: Heart or Heart-Lung TransplantationSSVD: Severe systolic ventricular dysfunction

Gallego P el al. Am J Cardiol 2012

Variable ToF TGA LVOT lesions

Fontan

Clinical Age at repairPrior shuntVentriculotomy incisionTransannular patch (pre) syncope

Longer FU timeSyncopePalpitationsNYHA > II

Longer FU timeSyncope

Longer FU timeSyncopePalpitationsOlder Fontantechnique

Hemodynamic RVSP > 60 mmHgRVOT > 40 mmHgModerate-severe PRRV dilatation RV dysfunctionLV dysfunctionRVOT aneurysmSustained VT

Systemic RV dysfunctionModerate-severe TR

LVOT > 50 mmHgSignificant ARHigh LV EDP LV dysfunctionLV hypertrophy

Ventriculardysfunction

ECG QRS duration > 180 msQRS fragmentationQT dispersionNSVTAtrial arrhythmiasHR variabilityHR turbulenceLate potentials

Atrial arrhythmiasQRS duration > 140 msComplete heart block

Atrial arrhythmias

CMR RV LGE RV LGE

Electrophysiological Inducible VT NO

DISEASE-SPECIFIC STUDIES

Khairy P et al, Heart Rhythm 2014

Clase I

Clase IIA

Fisiología biventricular con fracción de eyección del VI

sistémico ≤35% yCF NYHA II o III

Tetralogía de Fallot con múltiples factores de riesgo:

• Disfunción sistólica o diastólica del VI.

•Taquicardia ventricular no sostenida.

• Duracción de QRS > 180 msg.

• Fibrosis miocárdica extensa.

• Inducible taquicardia ventricular sostenida

Clase IIB

Ventrículo único o VD sistémico con fracción de eyección

<35%, particularmente si:

• arritmias ventriculares complejas

• síncope inexplicado

• CF NYHA II o III

• Duración de QRS > 140 msg

• Insuficiencia grave de válvula AV sistémica

Fracción de eyección del ventrículo sistémico < 35% en

ausencia de síntomas (CF NYHA I) u otros factores de riesgo

conocidos

Síncope de origen desconocido con Inducible TV sostenida

o FV en EEF

Síncope y CC moderada o compleja con alta sospecha

clínica de arritmia ventricular aunque el EEF no haya podido

definir la causa

Clase III

Enfermedad vascular pulmonar avanzada o síndrome

Eisenmenger

Priory SG et al. Eur Heart J 2015

Circ Arrhythm Electrophysiol 2017

Population: 157 deceased patients and controls36% cases and 16% controls: ICD recommendations according to guidelines

Applying guidelines: 59% cases and 65% controls, unrecognized

Spanish achd network

C. Hospitalario Jaén

H. Virgen del Rocio Sevilla

H. Virgen de las Nieves, Granada

• H. Vall d’Hebron, BCN• H Clinic, BCN

• H. U. La Paz, Madrid• H. Gregorio Marañón, Madrid• H. Ramón y Cajal, Madrid• H. 12 octubre, Madrid

H. La Fe, Valencia

H. Juan Canalejo, Coruña

H. Insular Las Palmas

H. Virgen de la Salud, Toledo

H. U. Salamanca

H. Universitario Elche

muticenter study on sudden cardiac death

207 confirmed sudden cardiac deaths

2014-2020

METHODS Gallego P, et al

ESC Congress 2019

Sudden cardiac deaths (SCD) & life-threatening ventricular

arrhythmias (LTVA) by specific defect

N = 71 Lesion-specific risk stratification

Actuarial Survival free

from SCD&LTVA

Gallego P, et al

ESC Congress 2019

Clusters HR (95%

CI)

p

Very-low Reference –

Low 2.8 (1.0-7.7) 0.048

Moderate 16 (6-45) <0.001

Severe 68 (26-181) <0.001

MULTICENTER CASE-CONTROL STUDY ON SUDDEN CARDIAC DEATH

21 centers

• 203 cases

• 2287 controls

SPANISH NETWORK FOR RESEARCH ON ACHD

Gallego P, et al

ESC Congress 2019

Adjusted R2 = 0.89

P<0.001

Gallego P, et al

ESC Congress 2019

Lesion-Specific Risk Stratification

C-indexStudy cohort Multicenter Study

ROC area lesion-specific risk stratification

AUC 0.811

95% CI 0.77-0.85

P<0.001

AUC 0.784

95% CI 0.75-0.82

P<0.001

Appropriate

shock excluded

Ventricular

arrhythmias

excluded

Gallego P, et al

ESC Congress 2019

Risk Prediction Model for SCD(National Institute of Health Carlos III, Research Project 17/01327)

1. Merging SCD with episodes of life-threatening

ventricular arrhythmias into a composite end-point.

2. Incorporating the baseline lesion-specific risk

stratification.

3. Including easily available demographic, clinical,

ECG, and echo variables

Oliver JM, et al

Submitted

Statistical Flow Chart

Oliver JM, et al

Submitted

Multivariate Risk ModelOliver JM, et al

Submitted

Model Performance in the Validation Dataset

CALIBRATION DISCRIMINATION

NRI = 1.17

95% CI = 0.98-1.36

p < 0.001

Oliver JM, et al

Submitted

Electronic Calculator

(http://cardioim.iisgmsai.org:48080/calc/)

Oliver JM, et al

Submitted

Prospective Evaluation

Control Group

N= 2,287 pts

FU 2017-2022

RECC Dataset

N≈ 6,000 pts

FU 2019-2022Risk Model

Outcomes at 3&5 yr.

•SCD

•LTVA

MetricsAnnual Incidence <0.2%

50 events

3 yrs – N > 8,000 pts

5 yrs – N > 5,000 pts

Spanish ACHD Network Investigators

José M Oliver, Pastora Gallego, Ana González, Pablo Ávila, Andrés

Alonso, Diego García-Hamilton, Rafael Peinado, Laura Dos, Antonia

Pijuan, Joaquín Rueda, Maria José Rodríguez Puras, Rocío García

Orta, Efrén Martínez Quintana, Raquel Prieto, Tomas Datino, José

Ruiz Cantador, Beatriz Bouzas Zubeldia, Isaac Martínez Bendayán,

Blanca Gordon, Javier Cantalapiedra, Víctor González Fernández,

Aleix Olivella, Francisco Buendía, Eduardo Moreno, Juan L

Rodríguez Hernández, Juan Robledo Carmona, Marta López,

Antonio García Honrubia, María Bastos Fernández, Gemma Lacuey,

Nuria Hernandez, Luis F Valenzuela, Joaquín Cano-Nieto, Iris de la

Puerta, Marta Noris, Beatriz García Aranda, Silvia Montserrat,

Inmaculada Sánchez, Javier Bermejo, Francisco Fernández-Avilés.

Lesion-specific Risk Stratification of

Sudden Cardiac Death and Ventricular Arrhythmias

in Adults with Congenital Heart Disease.

How to predict it?

Pastora Gallego, MD, PhDIntercenter Adult Congenital Heart Disease

Hospital Universitario Virgen del Rocio

Sevilla, Spain

On behalf of the Spanish ACHD Network Investigators

No conflict of interest to

disclose