FETAL TACHYARRHYTHMIASDIAGNOSIS & MANAGEMENT :

HOW TO BE SAFE AND MORE EFFECTIVE ?

Prof. Maurice GUIRGIS, MDFetal Cardiology unit

BICHAT Hospital – Université Paris 7LA ROSERAIE

FETAL SVTA LIFE THREATENING ARRHYTHMIAS

« PRENATAL CARDIAC EMERGENCY »

May lead to HF, hydrops & fetal death

Neonatal Morbidity & Morbidity (hydropic cases)

BACKGROUND

1st FETAL RECOGNIION OF SVT during labour SANCETTA 1952

FIRST REPORT TRANSPLACENTAL TTT OF HYDROPIC FŒTUS WITH SVT (With Digoxin) deliverd at term without hydrops HARRIGAN 1981

IN 2015 STILL NO CONSENSUS ON A UNIQUE MANAGEMENT STRATEGY

TOWARDS SAFEST /EFFECTIVE MANAGEMENT

4 Questions

WHAT IS THE MECHANISM?

WHAT IS THE FETAL TOLERANCE?

WHO TO TREAT?

HOW TO TREAT?

Q I WHAT IS THE MECHANISM?MECHANICAL CONSEQUENCE OF AV EVENTS

2D/M_MODE oldest

LV Inflow and outflow less effective A& E waves are fused/A absent /A systole not ass Vsystole

DOPPLER SVC/AO Fouron el al heart 2003

Doppler interogation of PA & PV Carvalho et al 2006

TISSUE DOPPLER IMAGING

FŒTAL MAGNETOCARDIOGRAPHY

FETAL ECHOCARDIOGRAPHYDOPPLER AO/SVC : VA & AV intervalls

(JC Fouron et coll Heart 2003)

NORMAL AV & VA SVT Short VA Type

FETAL ECHOCARDIOGRAPHYDOPPLER AO/SVC : AV & VA intervals

SVT Long VA Type

-Permanat J Reciprocarting T

-AEctopic Tachycardia

Q I WHAT IS THE MECHANISM?MECHANICAL CONSEQUENCE OF AV EVENTS & THEIR

RELATIONSHIP VA & AV Interval

SVT 1/1 AV SEQUENCE

73%

-MAINLY : Short VA <AV: Typical AV re-entry SVT +++

-RARE : Long VA>AV : Permanant JRT , AET

AF VARIABLE AV Block

26%AR usually >400 sustainedChaotic Non sustained

OTHERS RARE + bradycardia long QT to be

suspected Vt with AV dissociation

FETAL MAGNETOCARDIOGRAPHYFINE TUNE DIAGNOSIS

Wakai RT et coll Circ. 2003

Limited availability

High quality electrophysiological signals 1st Electrophysiologic document. :WPW , QRS aberrancy, multiple reentrant pathways, Initiation SVT AV RE- ENTRANTRANT TACHYCARDIA : PREDOMINANT MECHANISM

WITH HIGH INCIDENCE OF ACCESSORY AV CONNECTIONS

Hahurij ND et al Circ 2008

TDI signals stored as scan line raw data : analysis of activity within same cardiac cycle

TISSUE VELOCITY IMAGING Rein et al Circultion 2003/fetal kinetocardiogram

Fetal atrial flutter

TISSUE VELOCITY IMAGING

Fetal SVT : short VA AV re entry tachycardia

D’Alto J Cardiovasc Med 2008

Q2 FETAL CARDIAC TOLERANCE-SIGNS OF HF-

- SIGNS OF HYDRPOS RISK FOR HYDROPS

Sustained/Incessant (>50%)Nimrod 1987: Sustained Tmajor determinant (pacing f Lambs)

Heart Rate Gestational age Associated cardiac malformation 4-8% Ebstein,

AVC, ..

Q3 WHO TO TREAT?

NO HF/HYDROPS

LOW RISK

↓

WAIT & SEE POLICY

CLOSE FOLLOW -UP

HF + HYDROPS

NO HF HIGH RISK

↓ <35 WG : FETAL TTT NEAR TERM : CONSIDER

DELIVERY

Q3 HOW TO TREATPROBLEMS

THERAPEUTIC FETAL LEVEL (UNKOWN) NON INVASIVELY ( IV/IM /IC DIRECT FETAL

INJECTION CARRIES RISK) FETAL DRUG METABOLISM DEPENDENT ON

GA/PLACENTAL STATE & TOXIC EFFECTS? MATERNAL SIDE EFFECTS /TOXICITY CAN

BE CLOSELY MONITORED WHICH IS NOT THE CASE IN THE FETUS

Q 3 WHO TO TREAT?RATIONALE

IDEAL GOAL

RAPID CONVERSION TO SR

REGRESSION FETAL HF REGRESSION OF HYDROPS PROLONG PREGNANCY TO BIRTH

NEAR TERM

NO MATERNAL SIDE EFFECTS NO FETAL RELATED DEMISE : Proarhythmogenic /-ve inotropic effects

ACCEPTABLE

DECREASE ARRYHTHMIA BURDEN (DECREASE VENTRICULAR RATE )

IMPROVE FETAL HF RESOLVING HYDROPS SURVIVING TO VIABLE DELIVERY

MINI /NO MATERNAL SIDE EFFECTS NO FETAL RELATED DEMISE : Proarhythmogenic /-ve inotropic effects

DRUG ARSENAL IN 2014

DIGOXIN

FLECAINIDE

SOTALOL

AMIODARONE

VERAPAMIL

QUINIDINE

PROCAINAMIDE

PROPRANOLOL

DIGOXIN

SAFEST TRANSPLACENTAL TRANSFER - NO HYDROPS : 70-90% : ORAL DIGOXIN EFFECTIVE- HYDROPS : 20% : ORAL DIGOXIN FAILURE

ROUTE OF ADMINISTRATION- ORAL IN NON HYDROPIC CASES - INTRAVENOUS - DIRECT FŒTUS (IM 25 Inj /IC/ Parilla BV Am j Perinatol 1996- Hansmann et al 1985)

- CONVERSION RATES AS FIRST LINE TTT- SVT no hydrops 35-71%

- SVT , HYDROPS 10-40% BUT - FLUTTER WITH no Hydrops 45%

DIGOXIN MATERNAL PHARMAKOKINETICS DURING PREGNANY

Clinical and Pharmacologic Study of fetal supraventricular tachyarrhythmias

Azancot A, Jacqz Aigrin E, Guirgis M J Ped 1992

Increased Digoxin Plasma clearance & Short Elimination half life (Rise RBF& GFR)

DIGOXIN ABSORPTION & DISTRIBUTION DURING PREGNANCY

Azancot A, Jacqz -Aigrin E, Guirgis M J Ped 1992

Maternal :

- Decreased absorption (A secretion, motility..)

- Increased blood volume (30%)

- Drecreased circulating Digoxin levels

Hydropic placenta : decrease transfer

Retrospective & Prospective StudyAzancot A, Jacqz -Aigrin E, Guirgis M J Ped 1992

SURVEILLANCE

MATERNAL

Clinical, ECG, Electro..

S. Digoxin(<2ng/ml)

VIP: PRIOR TO TTT:

ENDOGENOUS DIGOXIN LIKE

IMMUNE COMPOUNDS (as high as 1.6ng/ml)

FETAL

Echocardiography

Fetal US + Doppler

Phonocardiography: % time in 8 hour period

European Study Protocol Of Fetal SVTJ of Maternal Fetal invest 1998

LOADING IV (5days)

-D1: 1mg/12 Hours

-D2-D3: 0.5mg/12 Hours

-D4-D5: 0,25mgx3 /day Mat.digoxinemias2ng/ml

Maternal tolerance

CONVERSION (<5d)-Oral Digoxin (0.5-1mg/d -3

devided doses) until term

NO CONVERSION-Oral Digoxin + 1 Drug

Amiodarone + or Flecainide

-DELIVERY

ACTUAL Protocol Of Fetal SVT

HF /HYDROPS IV IGOXIN (5days)

-D1: 0.5mg/D-D2-D5: 0.25mg/12 HoursAcc Mat.digoxinemias <2ng/ml &

Maternal tolerance

CONVERSION (<5d)-Oral Digoxin (0.25mgX 3)- Decrease until term

NO CONVERSION-Oral Digoxin + 1 Drug(Amiodarone + or Flecainide)-DELIVERY

NO HF/HYDROPSOral Digoxin

Digoxin 0,25X 3/d

Acc Mat.digoxinemias <2ng/ml & Maternal tolerance

CONVERSION (<12 d)

-Oral Digoxin (0.25mgX 3)- Decrease gradually until term

NO CONVERSION or HF-Oral Digoxin + 1 DrugAmiodarone + or Flecainide-DELIVERY

AMIODARONE

TRANSPLACENTAL : 10-30% Oral Loading 600mg x 3-4 (2-7d)/ Folowed by 200x3-4 dayl DIGOXIN (reduced ½ d)

SIDE EFFECTS

- TRANSIENT HYPOTHYROIDISM 15-20%-IUGR Frequent SPEECH Acquisition delay-Photosensitivity dermatitis & thrombocytopenia, QT long

Cuneo et al CIRC 2004Jouannioc et al Prental diagnosis 2003

FLECAINIDE

TRANSPLACENTAL 85% Oral 100mg-300mg/day

50-80% SUCCESS IN HYDROPIC FOETUS

FETAL DEMISE 18% in earlier studies

Allan Br heart J 1991: 12 (1 death)Simpson Heart 1998: 16 (3d in 24 hours; 1 in 15d)Jouanic Prenat Diag 2003: 7 ( 2d hours)Jaeggi et al 2011 : 35 (3d)

SOTALOL

Placental transfer : 50-90% 80mg orally x2day up to 160mg x 3 day High Efficacy in AF non hydropic fœtus INITIAL HIGH MORTALITY: 25-30%

(proarrhythmic effect more pronounced in fœtal heart)

? hydropic fœtus:4D/ 21 Oudijk et al Circulation 20002D/15 Jaeggi et al Circulation 2011

SAFETY REVISITED 2000-20111ST LINE SINGLE THERAPY FETAL DEMISE

HYDROPS DIGOXINE FLECAINIDE SOTALOL AMIODARONE

Jaeggi et al Circ 2011

33 4-

12-3 D

17-2D

Jouannic et al

Prenatal diagnosis 2003

26 7 -

-

-

12 2 D (16%)

1 TOP

7 SR(60%)

4-

1 TOP

2SR (50%)

PROTOCOLS SVT ARE VARIABLE

1ST LINE

NO HYDROPSDIGOXIN 80%

HYDROPS

DIGOXIN IV 5 days

Or FLECAINIDE orally

2ND LINE

Digoxin+ Flecainide Digoxin +Amiodarone

(Particularly if ventricular dysfunction)

CONCLUSIONSAFEST /EFFECTIVE TTT

PROPER ASSESMENT /MECHANISM, TOLERANCE MANDATORY PRIOR TO TREATMENT

MOTHER RISKS/FETAL RISKS SHOULD BE CAREFULLY ASSESSED

FAMILY INFORMATION ABOUT TREAMENT RISKD AND CONSENT

MORTALITY CONTINUES TO BE 10-17% for hydropic fœtus treated (Jaeggi et al, circulation 2011)

CONCLUSION

START WITH A MONOTHERAPY IS RECOMMENDED AVOID BLIND TRIALS INCREASE MATERNAL & FETAL RISKS

REAL DRUG EFFICACY WILL NOT BE DOCUMENTED

CONCLUSION

A PROSPECTIVE STUDY IS NOW URGENT

WHEN HYDROPS IS PRESENT

IV DIGOXIN (5days) IS SAFER (although LESS EFFECTIVE (0-20%) (NEED FOR A 2nd DRUG)

-AVOID POOR & ERRATIC ABSORPTION,

-RAPID PLACENTAL TRANSFER,

-FETAL PEAK PLASMA CONCENTRATIONS-RELATED EFFECTS

IF TT FAILURE: ASSOCIATION TO ONE DRUG: AMIODARONE OR FLECAINIDE WHILE KEEPING DIGOXIN

« OPTIMAL DRUG » RATHER THAN SPECULATIONS

Pour atteindre la vérité , il faut se défaire de toutes les opinions qu’on a reçues , et reconstruire de nouveau tout le système de ses connaissances.

René DESCARTES