1. ACQUIRED HEART DISEASES IN PREGNANCY ANTICOAGULATION IN PREGNANCY

2. 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

3. RHD dominates in non-western countries [56–89% ] Congenital heart disease [just 9–19%].
Eur J Heart Fail 2008;10: , Circulation 2001;104:

4. 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: )

5. 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
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

6. 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.

8. WHO CLASS II Most arrythmias WHO CLASS II/III Mild LV impairment VHD not included in class IV WHO CLASS III Mechanical valve

9. CLASS IV Pulmonary hypertension of any cause Previous PCM with LV impairment Severe MS and severe symptomatic AS Severe LV dysfunction

10. 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.

11. 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.

12. 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.

13. Fluoroscopy risks
Majority of procedures are < 1mGy to fetus RCR guidelines During the first 14 days of fertilization -no risk After 14 days major risk occurs if doses > 100mGy Doses <50 mGy –no risk mGy –risk not clear

14. Estimated radiation exposure

15. Valvular Heart Disease
Severity
Risk Stenotic lesions > Regurgitant lesion
Left sided diseases> Right sided disease
[ increased C.O. increased transvalvular gradient increased upstream pressures] vs. [ reduced SVR reduces Regurgitant volume]

16. 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:

17. 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.
MVR IN PREGNANCY

18. 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 cm2
Complications- CT , AF ,MR ,emboli, uterine contractions & labor

19. 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.

20. 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.

21. Pharmacological management of symptoms
MS with symptoms or PAH, restricted activities and β1-selective blockers are recommended. Diuretics are recommended when congestive symptoms persist despite β-blockers.
BMV
NYHA class III/IV or sys PAP > 50mm Hg, preferably after 20 weeks POG. [CI in asymptomatic women]
SPONTANEOUS ECHO CONTRAST-
Anticoagulation
Paroxysmal or Permanent AF, LA thrombus, prior embolism
Considered in mod/sev MS with spontaneous echo contrast, LA > 40ml/m2, low CO, CCF

22. 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.

23. 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)

24. 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.

25. CONTD….. Maternal risk HF 10%, Arrhythmias 3-25%(Pieper et al 2008)
Fetal risk- Preterm Labour, IUGR, LBW

26. 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.

27. Pre- pregnancy intervention
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
Emergency AVR in pregnancy
Delivery
Vaginal delivery + regional anesthesia in non-sev AS
LSCS in Sev AS

28. 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

29. 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
Tv repair in pregnanacy

30. 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 )
Pre pregnancy valvuloplasty

31. Severe PR with impaired RV function
Pre-pregnancy pulmonary valve replacement (preferably bioprosthesis) should be considered

32. Prosthetic valves Mechanical valves Bioprosthetic valves
Excellent H.D. Performances
Long term durability
Thrombogenic
Bioprosthetic valves
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%
PROSTHETIC RECOMMENDATIONS IN PREGNANCY

34. 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 IU followed by iu/hr for 72hrs

35. General Management Percutaneous intervention- CPBypass-
After 4th month in the second trimester [ organogenesis complete, fetal thyroid still inactive, volume of uterus small]
ACT b/w s
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

36. Peripartum cardiomyopathy
Eur J Heart Fail 2010;12:767–778.

37. Etiology Fas/Apo-1, C-reactiveprotein, IFN-g and IL-6
Cathepsin D in response to oxidative stress cleaves Prolactin into angiostatic & proapoptotic fragment 16 kDa Prolactin
Viruses
Autoimmune
CATHEPSIN D WHAT IS IT

38. Differential diagnosis
Eur J Heart Fail 2010;12:767–778.

39. Am J Obstet Gynecol 2008;199:415.e1-415.e5.
Natural history .
DETAILS N Engl J Med 2001;344:
Am J Obstet Gynecol 2008;199:415.e1-415.e5.

40. 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

41. 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)

42. FOLLOW UP Repeat echo after 6weeks, 6months and then annually
MRI at 6months and annually for accurate assessment of LV volumes and function

43. MANAGEMENT Similar to HF management
O2 administration to reach saturation of>95%
NIV and PEEP 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

44. 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)

45. Delivery need not be done in asymptomatics
Encouraged in deteriorating patients
Vaginal delivery encouraged but LSCS in critically ill patients
Left lateral position encouraged

46. Prognosis
No European studies
Vary geographically

47. 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.

48. Counselling LVEF <25% subsequent pregnancies discouraged
High risk of relapse in subsequent pregnancies
Elkayam et al and Habli et al ( 2 studies)

49. 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
Doppler USG for uteroplacental perfusion.

50. 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
Mild / , Severe ->or = 160/110mmHg

51. 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 hypertension
BP first recorded after 20 wks
Re- assessment after 42 days PP

52. Management
Non pharmacological- salt restriction, calcium supplementation
Low dose aspirin(75-150mg) at early onset<28 weeks
Weight gain- in normal kg
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 second choice.
Diuretics are not recommended.

53. Contd…
Management of crisis –iv Nitroprusside- caution 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

54. Recommendations in hypertension

55. CAD
3-6 / 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.
PCI in high risk NSTEMI only

56. 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

57. 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): )
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

58. 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 pregnancy and during pregnancy also. Implantation of PPI or ICDs -considered with echo guidance, especially if the fetus > 8 weeks gestation.

60. 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.
Echo guidance is used.

61. 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:

62. Anticoagulation Strategies Maternal outcomes- Chan et al(2000)
Valve thrombosis
Maternal mort.
3.9 %
OAC
2 %
9.2
UFH
OAC 4 35
UFH 15 9
LMWH
3.6
LMWH
OAC

63. 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 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:  

64. 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.

65. 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:

66. 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 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 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
OAC
UFH/L
UFH H
6 wks
12 wks
36 wks
6 hrs
6 hrs

67. Differences In strategy

68. BOOK REFERENCES BRAUNWALD`S HEART DISEASE HURST`S THE HEART
VALVULAR HEART DISEASE –WANG –VALVULAR HEART DISEASE IN PREGNANCY
TOPOL TEXTBOOK OF CARDIOVASCULAR MEDICINE

69. ARTICLES AND REVIEWS CARPREG study (Circulation.2001;104:515-21.)
Am J Obstet Gynecol 1998;179:1643–1653
Am J Cardiol 2006;97(8):
Am J Obstet Gynecol 2008;199:415
Circulation 2001;104:
Eur J Heart Fail 2008;10:
Eur J Heart Fail 2010;12:767–778
N Engl J Med 2001;344:
Arch Intern Med 2000;160:

70. THANK YOU