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
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
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
Top Related