Transcript ACQUIRED DISEASES OF PREGNANCY ANTICOAGULATION IN …

ACQUIRED HEART DISEASES IN
PREGNANCY
ANTICOAGULATION IN PREGNANCY
INTRODUCTION
• Prevalence of maternal heart disease -< 1%, its
presence increases the risk of adverse maternal,
fetal, and neonatal outcomes
• 0.2–4% of all pregnancies in western industrialized
countries. {Am J Obstet Gynecol 1998;179:1643–1653.}.
In western countries maternal heart disease is now the
major cause of maternal death during pregnancy
• RHD dominates in non-western countries
[56–89% ]
Congenital
heart disease [just 9–19%].
Eur J
Heart Fail 2008;10:855-860, Circulation 2001;104:515-521.
STUDY
• A Canadian study analyzed the outcomes of pregnancy
in a group of women with congenital or acquired heart
disease (562 women and 599 pregnancies)
CARPREG study (Circulation.2001;104:515-21.)
Maternal outcomes
• Incidence of adverse maternal cardiac events
– 13% of completed pregnancies
– More likely if:
• EF below 40%
• Left heart obstruction (AS with a valve area of less than 1.5 cm2 or
MS with a valve area of less than 2.0 cm2)
• Previous cardiovascular events or arrhythmia
• NYHA class > II or cyanosis.
•
These events occurred in:
–
–
–
–
4% of the women with none of these risk factors
27 % of those with one risk factor
62 % of those with two or more risk factors
The 3 women that died had two or more risk factors
Sui et al
Fetal outcomes
• NYHA class III or IV and left heart obstruction were predictors
of fetal outcomes also.
• Other predictors of adverse fetal outcomes include:
•
•
•
•
The use of anticoagulant drugs
Smoking during pregnancy.
Multiple gestation.
Mother’s age (> 35 yrs or < 20 yrs).
ZAHARA study
• Fetal mortality :
• 4 % among pregnancies in women with one or more of these risk
factors.
• 2% among those with none of these risk factors.
WHO CLASS II
Most arrythmias
WHO CLASS II/III
Mild LV impairment
VHD not included in class IV
WHO CLASS III
Mechanical valve
CLASS IV
Pulmonary hypertension of any cause
Previous PCM with LV impairment
Severe MS and severe symptomatic AS
Severe LV dysfunction
Evaluation
• The evaluation- Pre conceptional and entail a full cardiac
assessment.
H/o exercise capacity, current or past evidence of heart failure
and associated arrhythmias.
• Cardiac hemodynamics -PAP and the severity of valve
dysfunction - assessed by echo.
• Exercise testing - Assessment of functional capacity.
• During pregnancy evaluation of each trimester - Assess any
deterioration in maternal cardiac status.
INVESTIGATIONS -ECHO
• Gradients in RVOT and LVOT increase
• Increased stroke volume cause increase in
severity of regurgitation.
• LVEDD increased
• TEE can be performed safely
• Fetal echo best in 20 weeks gestation.
TMT
•
•
•
•
80% of predicted heart rate
No evidence of spontaneous abortion
Dobutamine stress should be avoided
Assessment of myocardial reserve pre
pregnancy in PPCM & VHD
• Nuclear stress tests are avoided.
Fluoroscopy risks
Majority of procedures are < 1mGy to fetus
RCR -2009 guidelines
During the first 14 days of fertilization -no risk
After 14 days major risk occurs if doses >
100mGy
Doses <50 mGy –no risk
50-100 mGy –risk not clear
Estimated radiation exposure
Valvular Heart Disease
Severity
• Risk Stenotic lesions > Regurgitant lesion
• Left sided diseases> Right sided disease
MS
•
Poorly tolerated [ moderate & severe MS]- Tachycardia, increased plasma
volume
•
PHT, Trans valvular gradients, PAP measurements are less reliable marker of
severity
•
Maternal Risks- HF symptoms, Pulmonary edema in II & III trimester. AF
[increases risk of T.Emb, pulmonary edema] ( El Kayam etal, 2005 JACC)
•
Moderate & severe MS counseled against pregnancy without prior
intervention
Fetal risks- prematurity 20-30%; IUGR 5-20% ( El Kayam & Hameed 2001) &
Silversides
JACC 2001: 37:893-899
•
MS INTERVENTIONS
• NYHA III or IV patients or valve area less than
1 cm2 , BMV or MVR before pregnancy.
• BMV - second trimester in NYHA III/ IV or with
PAP above 50 mm Hg despite optimal medical
therapy.
• MVR during pregnancy- high fetal loss (30%)
hence reserved till all measures fail and
mother`s life is in danger.
• Anticoagulation in AF OR in bed rest.
BMV OUTCOMES
• BMV in pregnancy KEM study (Gupta et al) –
successful outcomes of 40 pregnancies.
• Ribeiro et al (1992)study on maternal outcomes
in 78 patients-8 patients developed mod MR, No
evidence of PE
• De Souza et al(2001) compared the outcomes of
PBMV v/s OMC in 21 pts with severe MS -38%
fetal death in OMC
• Current consensus –PBMV to symptomatic
patients with severe MS with OMT/ MVA 0.751.2cm2
PERIPARTUM MANAGEMENT
• Vaginal delivery is the usual approach.
• Avoidance of volume overload and
tachycardia is the main hemodynamic goal.
• In unstable patients, monitoring with arterial
line and PCWP aids in optimum hemodynamic
management.
PERIPARTUM MANAGEMENT
• Epidural analgesia.
• Assisted-delivery devices during the second stage of
delivery eliminate hemodynamic effects of valsalva
maneuver during “pushing”.
• Caesarean section for obstetrical indications.
Pharmacological management of symptoms
MS with symptoms or PAH, restricted activities and β1selective blockers are recommended. Diuretics are
recommended when congestive symptoms persist despite βblockers.
BMV
NYHA class III/IV or sys PAP > 50mm Hg, preferably after 20
weeks POG. [CI in asymptomatic women]
Anticoagulation
•Paroxysmal or Permanent AF, LA thrombus, prior embolism
•Considered in mod/sev MS with spontaneous echo contrast, LA >
40ml/m2, low CO, CCF
MITRAL REGURGITATION
• Well tolerated due to reduction in SVR.
• Women with symptomatic MR may benefit
from mitral-valve surgery (preferably
repair))before becoming pregnant.
• Diuretics may be indicated.
• Outcome data that would help to guide
clinical decision making in this area are
lacking.
AORTIC STENOSIS
• Congenital valvular abnormalities are usually
the cause of AS in young women in the US.
• Severe AS is poorly tolerated during
pregnancy.
• Maternal and perinatal mortality of 17% and
32% respectively have been reported.
(Pieper et al 2008)
AORTIC STENOSIS
 Symptomatic patients - peak outflow gradient >
50 mm Hg are advised to delay conception until
after surgical correction.
 Termination of pregnancy- if patient is
symptomatic before the end of the 1st trimester.
 Even severe AS may be asymptomatic
 Aortic-valve replacement and palliative aortic
balloon valvuloplasty have been performed during
pregnancy with associated maternal and fetal risk.
CONTD…..
• Maternal risk HF 10%, Arrhythmias 325%(Pieper et al 2008)
• Fetal risk- Preterm Labour, IUGR, LBW
PERIPARTUM MANAGEMENT
• Vaginal delivery is the usual approach.
Oxytocin may decrease the SVR and increase PAP.
Epidural analgesia may be given.
Avoid sudden decrease in SVR.
• Cesarean section
GA has traditionally being advocated to avoid sudden
decreases of SVR.
Case reports of regional anesthesia with positive outcomes.
Pharmacological management of symptoms
HF- treat with diuretics
AF- b-blockers, CCB to control HR, Digoxin also may be
used
Pre- pregnancy intervention
•Symptomatic severe AS
•LVEF<50%, severe LVH (PW> 15mm)
•TMT- symptoms or falling BP
•Recent progression of AS
•Asc. Aorta> 50 MM (27.5mm/m2)
During Pregnancy
Severe symptomatic AS + refractory to medical therapy/
life threatening symptoms Non calcified valve may be
subjected to BAV/ emergency AVR
Delivery
•Vaginal delivery + regional anesthesia in non-sev AS
•LSCS in Sev AS
Aortic Regurgitation
• Root dilatation (Marfan syndrome ),Bicuspid Aortic
valve, and RHD are the commonest causes.
– The reduced SVR of pregnancy reduces the
volume of regurgitated blood
– Women with an abnormal functional capacity or
left ventricular dysfunction are predicted to have a
high risk of abnormal maternal outcomes, but few
data concerning this population are available
Tricuspid valve lesions
• Better tolerated
• Maternal risk- HF, Arrhytmias, Progressive worsening of regurgitations
• Moderate to severe Regurgitant lesions may undergo exercise testing to
decide pre pregnancy intervention
• Severe lesions + symptoms/ impaired LV function/ Ventricular dilatation 
treated surgically, if possible repair
• TV repair if moderate Secondary TR with annular dilatation >40mm,
usually during left sided valve surgeries
PS & PR
PS is generally well tolerated
– Complications of sev PS- RV failure & Arrhythmias
– Pre pregnancy balloon valvuloplasty in severe
stenosis (peak Doppler gradient > 64 mmHg)
– LSCS is considered in patients with severe PS and
in NYHA class III/IV despite medical therapy and
bed rest, in whom percutaneous pulmonary
valvotomy cannot be performed or has failed.
Hameed et al ( JACC
2003 )
Severe PR with impaired RV function
– Pre-pregnancy pulmonary valve replacement
(preferably bioprosthesis) should be considered
Prosthetic valves
Mechanical valves
Bioprosthetic valves
• Excellent H.D.
Performances
• Long term durability
• Thrombogenic
• Good H.D Performances
• Much less thrombogenic
• High risk of valve
degeneration [~50% women
<30yrs at 10 yr post
implant]
– M> A,T position
– Reoperation mortality risk
addl 5%
Management of valve thrombosis in
pregnancy
• Presents as embolism or dyspnoea
• TTE and then TEE is required. If still not confirmed a
fluoroscopy is done
• Fibrinolysis is recommended
• ESC 2010 guidelines - anticoagulation optimisation
for small clots
• Thrombolysis has shown little negative effects on
fetus
• Streptokinase bolus of 250000 IU followed by
100000 iu/hr for 72hrs
General Management
• Percutaneous intervention– After 4th month in the second trimester [
organogenesis complete, fetal thyroid still inactive,
volume of uterus small]
– ACT b/w 200-300s
• CPBypass– 13th & 28th week [Fetal malformation - I trim &
maternal complication - III trim]
– 3-6% late neurological impairment in children, high
fetal mortality hence Sx only when refractory to
medical therapy, interventional procedures fail,
mother’s life threatened
Peripartum cardiomyopathy
Eur J Heart Fail 2010;12:767–778.
Etiology
Cathepsin D in response to
oxidative stress cleaves
Prolactin into angiostatic &
proapoptotic fragment 16 kDa
Prolactin
Fas/Apo-1, C-reactiveprotein,
IFN-g and IL-6
Viruses
Autoimmune
Differential diagnosis
Eur J Heart Fail 2010;12:767–778.
Natural history
.
Am J Obstet Gynecol 2008;199:415.e1-415.e5.
PRESENTATION
• First 4 months after delivery- most of them(78%)
• Last month of pregnancy- 9%
• > than 4months after delivery or before 1month of pregnancy 13%
CLINICAL FEATURES
• Features of right heart or left heart failure or both
• Can present as ventricular arrythmia
• 92% heard a third heart sound (2005 South African study)
• LV thrombosis is seen
INVESTIGATIONS
•
•
•
•
Diagnosis of exclusion
ECG – 66% LVH, 96% ST-T changes
Elevated BNP and NT pro BNP
Echo – Not all have LV dilatation and
LVEDD>60 predicts poor recovery
• MRI is a better predictor of LV functions and
assesses the chamber volumes better.( Late
gadolinium enhancement)
FOLLOW UP
• Repeat echo after 6weeks, 6months and then
annually
• MRI at 6months and annually for accurate
assessment of LV volumes and function
MANAGEMENT
•
•
•
•
•
•
Similar to HF management
O2 administration to reach saturation of>95%
NIV and PEEP 5-7.5 cm H2O
Loop diuretics and NTG
Inotropics when required
Pts after OMT and IABP ,the pt may require
assist device or cardiac transplantation
LVAD used as bridge to transplantation or
destination therapy
Management of stable heart failure
• ACEI and ARB avoided
• Hydralazine and nitrates combination used
safely
• Beta 1 selective agents are preferred
• LMWH and UFH used in pregnancy
• Role of CRT AND ICD- pt with LV dysfunction
for 6 months post presentation
• Bromocriptine- used in acute stage- 2.5mg bd
(Denise etal 2007)
• Delivery need not be done in asymptomatics
• Encouraged in deteriorating patients
• Vaginal delivery encouraged but LSCS in
critically ill patients
• Left lateral position encouraged
Prognosis
• No European studies
• Vary geographically
SA- 6m & 2yr
mortality
rates 10% &
28%.
Brazil & Haiti
6m rate 14–
16%
Turkey- 4yr
rate 30%
LV func.
returns
to normal in
23–41%
Eur J Heart Fail 2010;12:767–778.
Counselling
• LVEF <25% subsequent pregnancies
discouraged
• High risk of relapse in subsequent pregnancies
Elkayam et al and Habli et al ( 2
studies)
Hypertensive disorders
• Accounts for 15% of all pregnancies
• BP recordings in lateral recumbent posture
• Ambulatory BP monitoring is superior
• Investigations – LFT, RFT, urine r/e, Uric acid ,
Hct
• Proteinuria >2g/d –close monitoring
>3g/d – delivery
VMA and plasma metanephrine analysis along
with USG abdomen
Classification
• Pre existing hypertension
• Gestational hypertension
• Pre existing hypertension with superimposed
gestational hypertension with proteinuria
• Antenatally unclassifiable hypertension
• Hypertension defined as SBP> or = 140 & DBP >
or = 90
Hypertensive disorders
Type
Criteria
Comments
Pre-existing HTN
>140/ 90 mm Hg, either
precedes pregnancy or develops
<20 weeks gestation
Usu. Persists after 42 days PP;
1-5% of pregnancy
Gestational HTN
>140/ 90 mm Hg, develops >20
weeks gestation
Usu resolves within 42 days
PP; 6-7% pregnancy
Pre-eclampsia
Gest HTN +
proteinuria[>0.3g/day or
>30mg/mmol U. creatinine]
•Upto 25% of prev HTN
Eclampsia
Pre-eclampsia + seizures
Immediate termination of
pregnancy required
Pre-existing HTN +
superimposed
gestational HTN with
proteinuria
Pre-existing HTN+ further
worsening of BP+ proteinuria
[>0.3g/day] after 20 wks
Antenatally unclassifiable BP first recorded after 20 wks
hypertension
Re- assessment after 42 days
PP
Management
• Non pharmacological- salt restriction, calcium
supplementation
• Low dose aspirin(75-150mg) at early onset<28
weeks
• Weight gain- in normal 11.2-15.9kg
• Pharmacological management- all drugs can
be continued except Renin inhibitors , ACEI
and ARBs.
• Severe hypertension iv Labetalol or
metaprolol can be used. CCBs are drugs of
Contd…
• Management of crisis –iv Nitroprussidecaution on cyanide toxicity.
• Patient with pulmonary edema can be
managed with iv Nitroglycerin
• Methyldopa should be avoided postpartum
because it causes depression.
• Earlier the onset of HT in pregnancy the more
the chance of recurrence in next pregnancy
Recommendations in hypertension
CAD
• 3-6 /100000 deliveries.
• Coronary artery dissection is a common
cause.(LAD is the common culprit artery).
• Aortic dissection, pulmonary embolism and pre
eclampsia also to be ruled out in pregnant
women with chest pain
• Trop I is a useful investigation.
• PCI treatment of choice in STEMI.
Contd…
• PCI preferred to thrombolysis as it will cover
up dissections as well
• BMS Stents are used
• CABG carries an extremely high mortality
• DRUGS- ASA , beta blockers are safe but safety
of clopidogrel is not known
• Vaginal delivery is most appropriate
Tachyarrhythmia
• Premature extra beats / sustained tachyarrhythmias become more
frequent and may even manifest for the first time during pregnancy
• PSVT in 20-44% of pregnancy. (Am J Cardiol 2006;97(8):1206-1212)
• Immediate electrical cardioversion - a/c Rx of any tachycardia with
haemodynamic instability
• For acute conversion of PSVT- vagal manoeuvre followed by I.V. adenosine
is recommended. I.V. metoprolol or propranolol can also be considered
• For long-term management of SVT -oral digoxin or metoprolol/propranolol
is recommended. If not successful oral sotalol or flecainide may be used
Arrhythmia
• Immediate electrical cardioversion of VT is
recommended for sustained, unstable &
stable VT .
• I.V. Sotalol or Procainamide - a/c conversion of
sustained, haemodynamically stable and
monomorphic VT.
• Oral metoprolol, propranolol or verapamil idiopathic sustained VT (Long-term
management). If unsuccessful  oral sotalol,
flecainide, propafenone
• ICD implantation, recommended prior to
Bradyarrythmia
• Rare
• Favourable outcome
• 30% of congenital AV blocks present during
pregnancy
• Vaginal delivery carries no extra risks
• Temporary pacing in patients with CHB with
symptoms
• Permanent pacing can be done once fetus is >
8weeks of age.
Anticoagulation
• No results of RCT to guide the choice of anticoagulant
therapy during pregnancy.
• Monitoring to assess whether the antithrombotic effect is
adequate.
• The effective doses of these drugs change during pregnancy
because of changes in intravascular volume and body
weight.
• In a series of 976 women with a total of 1234 pregnancies
the use of any anticoagulant therapy resulted in major
bleeding in 2.5 % of the pregnancies, with bleeding usually
occurring at the time of delivery. Arch Intern Med 2000;160:191-196
Anticoagulation Strategies
Maternal outcomes- Chan et al(2000)
Valve thrombosis
Maternal mort.
3.9 %
9.2
OAC
UFH
OAC
35
UFH
9
LMWH
3.6
LMWH
2%
4
15
OAC
OAC
• In women with mechanical valves the use of OAC - Greatest
maternal protection.(Risk of thromboembolism- 3.9%, risk of
death-1.8%).
• High rate of fetal loss including spontaneous abortions,
stillbirths, and neonatal deaths (30%).
• Exposure to warfarin between 6 -12 wks -fetal loss twice that
associated with the use of UFH
• Fetopathic effects - (nasal hypoplasia and bone stippling)
occurred in approximately 6 % of cases in doses > 5mg
Vitale et al - J Am Coll Cardio 1999;33:1637-41.
Heparin
• If heparin rather than warfarin was used during the 1st
trimester, the risks of maternal thromboembolism and
maternal death more than doubled (9.2% and 4.2%
respectively).
• The use of heparin throughout pregnancy was associated
with the highest risks of maternal thromboembolism and
maternal death (25% and 7 % respectively).
• Long-term use of heparin - HIT and osteopenia.
Arch Intern Med 2000;160:191-6.
LMWH
• Lower risks of thrombocytopenia and osteopenia
than UFH
• There are insufficient data from studies of women
with prosthetic heart valves to support the efficacy
of this therapy.
• No data regarding the use in AF with valvular
disease.
• To be monitored with anti X a levels. Target 6 hr post
dose 0.8 to 1.2 U/ mL.
J CardioPharmacol Ther 2004;9:107-15.
Anticoagulation Strategies
• OAC throughout pregnancy best strategy [esp. if warf <5 mg, Acitrom
(acenocoumarol) <2 mg]
• Discontinuation of OAC b/w 6 &12 wks and replacement by UFH (a PTT
≥2× control; infusion in high risk pts) or LMWH twice daily (according to
weight and target anti-Xa level 4-6 hours post-dose 0.8-1.2 U/mL in
patients with a warfarin dose required of >5 mg/day
• OAC discontinued and UFH (a PTT ≥2× control) or adjusted-dose LMWH
(anti-Xa level 4-6 hours post-dose 0.8-1.2 U/mL) started at the 36th week
• LMWH replaced by i.v. UFH at least 36 hours before planned delivery. UFH
to be continued until 4-6 hours before planned delivery and restarted 4-6
hours after delivery if there are no bleeding complications
• If delivery starts on OACs, LSCS indicated to prevent fetal bleed
OAC
UFH/L
6 wks
OAC
12 wks
UFH/L
36 wks
UFH
6 hrs
H
6 hrs
Differences In strategy
BOOK REFERENCES
• BRAUNWALD`S HEART DISEASE
• HURST`S THE HEART
• VALVULAR HEART DISEASE –WANG –
VALVULAR HEART DISEASE IN PREGNANCY
• TOPOL TEXTBOOK OF CARDIOVASCULAR
MEDICINE
ARTICLES AND REVIEWS
CARPREG study (Circulation.2001;104:515-21.)
Am J Obstet Gynecol 1998;179:1643–1653
Am J Cardiol 2006;97(8):1206-1212
Am J Obstet Gynecol 2008;199:415
Circulation 2001;104:515-521
Eur J Heart Fail 2008;10:855-860
Eur J Heart Fail 2010;12:767–778
N Engl J Med 2001;344:1567-71
Arch Intern Med 2000;160:191-196