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Acquired heart disease and pregnancy

Acquired heart disease and pregnancy. Dr Sherief. Contents. Introduction General principles Valvular heart disease Infective endocarditis ACS in pregnancy Peripartum cardiomyopathy Prosthetic valves in pregnancy Post cardiac transplantation patients. Introduction.

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Acquired heart disease and pregnancy

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  1. Acquired heart disease and pregnancy Dr Sherief

  2. Contents • Introduction • General principles • Valvular heart disease • Infective endocarditis • ACS in pregnancy • Peripartumcardiomyopathy • Prosthetic valves in pregnancy • Post cardiac transplantation patients

  3. Introduction • Developed countries • Women with heart disease : ̴ 1 % of the obstetric population • Many women are postponing childbearing until the fourth and fifth decades of life • Advancing maternal age • HTN, DM, DLP become more common • Valvular heart disease, prosthetic valves, ACS, PPCM

  4. Heart disease in pregnancy - General principles Assessing risk Predictors of cardiac events • Severity of valve lesions • Degree of ventricular dysfunction Cardiac evaluation: The history, physical examination, echocardiogram and ECG form the foundation of in all patients Siu SC et al. Risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997 • Retrospective study • Analyzed outcomes of 221 women with heart disease who underwent 252 pregnancies (excluding miscarriages) The findings were then applied in a prospective study Siu SC et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001 • 562 women with cardiac disease or arrhythmias who had 617 pregnancies

  5. Heart disease in pregnancy - General principles Results The four predictors of cardiac events identified: • Poor functional class (NYHA class II to IV) or cyanosis • Previous cardiac event (HF, TIA, stroke) or arrhythmia • Left heart obstruction (MVA <2 cm2, AVA <1.5 cm2, peak LVOT gradient >30 mmHg) • LV systolic dysfunction (LVEF <40 %) One point was assigned for each finding • The actual rate of primary cardiac events (pulmonary edema, arrhythmia, stroke, cardiac arrest or death) -- 13% • 55% of events occurred antepartum There was excellent agreement between the predicted and observed rates by risk score

  6. Heart disease in pregnancy - General principles • Neonatal outcome also correlates with the maternal risk score • Neonatal complications • Risk score ≥1 : 33% • Risk score 0 (no HD) : 11% Siu SC et al. Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 2002 • Risk scores of ≥1 • More frequent evaluations and close collaboration between the patient's cardiologist and obstetrician • Individuals at greatest risk should be referred to a maternal-fetal medicine specialist (high-risk obstetrician) for management of pregnancy

  7. Heart disease in pregnancy - General principles Management of labor and delivery • Vaginal delivery – For almost all • Induction of labor • Prostaglandin analogues are absorbed into the systemic circulation and can lower SVR, lower BP and increase HR • These effects are more frequent with E2 than E1 • Cesarean delivery should be reserved for obstetric indications • The concerns about cesarean delivery include: • GA, if required, incurs the risk of hemodynamic instability associated with intubation and the anesthetic agent • Blood loss that is about twice as great as with vaginal delivery • Increased risks of wound and uterine infection • Postoperative thrombophlebitisis more common after cesarean delivery • The risk of postoperative incisional bleeding is high in patients requiring anticoagulants

  8. Heart disease in pregnancy - General principles Selection of mode of anaesthesia Anesthesia/analgesia • IM or IV opiates may be used to relieve pain and apprehension • Lumbar epidural anesthesiais highly effective for controlling labor pain • Lowers pain-induced elevations of sympathetic activity • Reduces the urge to push • Provides excellent anesthesia for operative procedures • The epidural should be dosed slowly with local anesthetics since venous return can be reduced by the anesthetic • Single shot spinal  Rapid decrease in preload and afterload Contraindicated in some cardiac lesions (MS, AS) Hemodynamic monitoring • Systemic arterial pressure and HR • Pulse oximetry • Continuous ECG monitoring • A Swan-Ganz catheter for hemodynamic monitoring should not be routinely employed • In labor • Lateral decubitus position to attenuate the hemodynamic fluctuations associated with major uterine contractions and the supine position • Let it come; DON’T let her push • Undesirable circulatory effects of the Valsalvamaneuver • Allow the forces of labor to descend the fetal head to the perineum, unassisted by maternal pushing • Delivery may then be assisted by low forceps or vacuum extraction

  9. Heart disease in pregnancy - General principles Fetal monitoring • The growth restricted fetus is especially vulnerable to hypoxia during labor • Continuous electronic FHR monitoring is recommended Postpartum care • After expulsion of the placenta, bleeding is reduced by uterine massage and iv oxytocinadministration • Oxytocin should be infused slowly (< 2 units/min) to avoid hypotensive effects • Prostaglandin F analogues (for PPH) -- Increase in PA pressure • Methylergonovine should be avoided because of the high rate (>10 %) of vasoconstriction and elevation of systemic pressure • Hemodynamic monitoring of the mother is warranted for 12 to 24 hours after delivery • DVT prophylaxis -- meticulous leg care, elastic support stockings and early ambulation

  10. Valvular heart disease in pregnancy Valvular heart disease • Study of pregnancy complicated by RHD (519 patients) • MS : 61% • MR : 33% • AR : 6% McFaul PB et al. Pregnancy complicated by maternal heart disease. A review of 519 women. Br J ObstetGynaecol 1988

  11. Valvular heart disease in pregnancy Risk according to valve lesion ACC/AHA 2006 valvular guidelines (2008 focused update) and the 2007 ESC guidelines Settings associated with high maternal and/or fetal risk: • Severe AS with or without symptoms • Symptomatic MS (NYHA class II to IV) • AR or MR with NYHA class III to IV symptoms • Aortic and/or mitral valve disease with severe LV dysfunction (LVEF < 40%) or severe PAH (PAP >75% of systemic pressure) • Marfan syndrome with or without AR • Mechanical prosthetic valve requiring anticoagulation Settings associated with low maternal and/or fetal risk: Asymptomatic AS with an LVEF >50% and a mean gradient < 25 mmHg AR / MR with no or mild symptoms (NYHA class I to II) MVP with mild to moderate MR with an LVEF >50 % Mild MS (MVA >1.5 cm2and a mean gradient < 5 mmHg) without severe PAH (PAP >75% of systemic pressure) Mild to moderate PS

  12. Valvular heart disease in pregnancy Cardiac surgery • Delay surgery (if possible) until the fetus is viable • Cesarean delivery as part of a combined procedure • Best time for surgery -- Second trimester • Potential risks of teratogenicity from medication • X-ray exposure • Premature delivery Clinical course and management of valve disease • Cardiac surgery should be avoided, if possible, during pregnancy • Maternal risks : Same as in nonpregnant women • Cardiopulmonary bypass  Significant risk for the fetus • Early pregnancy with one of the high risk valve lesions  Termination of pregnancy  Corrective surgery (before another attempt at pregnancy) is recommended • If the mother declines termination  Medical management (as per ACC/AHA guidelines)  Intervention (only for refractory NYHA class III or IV symptoms) Low

  13. Mitral stenosis in pregnancy •  MS in women of childbearing age is nearly always rheumatic in origin • Women with RHD (MS being most common) : <25% of the pregnant women with heart disease (US and Canada) • MS is a common condition in pregnant women where RHD is prevalent • Report of 1194 pregnancies in women with heart disease in three studies (Brazil, Turkey and Senegal) -- RHD was the underlying cause in 56-88% of womenAvila WS et al. Pregnancy in patients with heart disease: experience with 1,000 cases. ClinCardiol 2003 Diao M et al. Pregnancy in women with heart disease in sub-Saharan Africa. Arch CardiovascDis 2011

  14. Impact of cardiovascular changes in pregnancy in women with MS ANTEPARTUM LABOUR

  15. Relationship between severity of MS and impact of pregnancy • Severity of MS – Directly related to the risk of maternal and fetalcomplications • There is an incremental increase in the frequency of maternal and fetal complications with increasing severity of MS • Risk factors for maternal cardiac complications • H/o cardiac complications • pulmonary edema, arrhythmias, TIA or stroke prior to pregnancy • poor baseline maternal functional class • Pregnancy has any subsequent effect on the progression of disease or symptoms in women with MS? No contemporary studies

  16. Summary of pregnancy outcomes in women with mitral stenosis References:HameedA et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am CollCardiol 2001; 37:89 Silversides CKet al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol 2003; 91:1382.

  17. Nature and frequency of adverse pregnancy outcomes Maternal outcomes • In the four largest contemporary series from North America and Europe 300 pregnant women with MS - No maternal deaths 1 stroke Madazli R et al. Pregnancy outcomes in women with heart disease. Arch GynecolObstet 2010 Hameed A et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am CollCardiol 2001 Leśniak-Sobelga A et al. Clinical and echocardiographic assessment of pregnant women with valvular heart diseases--maternal and fetal outcome. Int J Cardiol 2004 Silversides CK et al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol 2003 • 448 pregnant patients with RHD (88 patients with MS ; 54 had moderate to severe MS) 8 deaths - 1.4% mortality (HF due to severe native mitral disease) 8 episodes of thromboembolism Avila WS et al. Pregnancy in patients with heart disease: experience with 1,000 cases. ClinCardiol 2003 Study of 46 pregnant women with MS from sub-saharan Africa Maternal mortality rate was 32 % Diao M et al. Pregnancy in women with heart disease in sub-Saharan Africa. Arch CardiovascDis 2011

  18. Nature and frequency of adverse pregnancy outcomes • AF is the most common arrhythmia • 20% of the pulmonary edema episodes occurred in the setting of atrialtachyarrhythmias Silversides CK et al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol 2003 • The peak period of maternal cardiac complications is during the second and third trimester • In the two largest North American series (total of 126 pregnancies) Deterioration of one NYHA class - 74% Two NYHA classes - 40% Silversides CK et al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol 2003 Hameed A et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am CollCardiol 2001 Fetal outcomes • Perinatal complications • premature labor • low fetal weight • perinatal death More frequent with increasing severity of MS and in the presence of complications

  19. Mitral stenosis in pregnancy - Evaluation Risk stratification • Highest risk of maternal cardiac complications • Moderate or severe MS (MVA <1.5 cm2) • Baseline maternal NYHA class III or IV • H/o cardiac complications prior to pregnancy • Pulmonary edema • Arrhythmias • TIA or stroke • Central cyanosis • LV dysfunction • PAH (PASP >60 mmHg) -- ? additional risk factor (Findings not uniform in contemporary studies)

  20. Mitral stenosis in pregnancy - Evaluation Frequency of cardiac follow-up • Determined by the risk level • The 2011 ESC guidelines • Monthly or bimonthly follow-up for moderate to severe MS (MVA < 1.5 cm2) • At every trimester and prior to pregnancy for mild MS • No specific recommendations for echocardiographic assessments • At the minimum 2 ECHO studies • First antepartum visit • Third trimester visit • Transmitral gradient will increase as pregnancy progresses • PHT and planimetry : Less preload dependent methods to measure MVA • PASP may also increase

  21. Mitral stenosis in pregnancy - Management • The preferred time for PMBV is in the 22 to 26 week • Minimizes the radiation risks to the developing fetus • Fetal survival is unlikely if emergent delivery is precipitated • Maternal and fetal risk is substantial if PMBV is delayed in severe MS • Efficacy of PMBV Study of 45 pregnant women who underwent PMBV or surgical mitral valve commissurotomy for severe heart failure • Procedural success rate of PMBV - 95% • Improvement in symptoms - same in both groups • Fetal complications were less frequent • Fetal and neonatal mortality were lower with PMBV (5 Vs 38% ) de Souza JA et al. PBMV in comparison with OMV commissurotomy for MS during pregnancy. J Am CollCardiol 2001 Peripartum • Regional anesthesia Attenuate the spikes in CO during labor • Almost all can undergo vaginal delivery with an assisted second stage • Caesarian : Reserved for obstetric indications and in whom anticoagulation cannot be reversed • Refractory HF requiring intubation and ventilation -- Only cardiac indication for CS • Endocarditis prophylaxis is not routinely recommended for uncomplicated vaginal or cesarean delivery Postpartum • Intensive monitoring • Anticoagulation (if required) can be resumed once there is no evidence of early or late PPH • No specific guidelines on the timing of postpartum assessments • Cardiac assessment at 4-6 weeks postpartum • Screen for postpartum deterioration • Adjust cardiac medications • Discuss contraception choices • Most cardiac medications are excreted in breast milk • Small amounts • Use is generally safe • An exception is Amiodarone : Breastfeeding is contraindicated during maternal use of Amiodarone • Oral contraceptives • Estrogen-based OCP • Except for those with increased thromboembolic risk • Severe MS, PHT, NYHA IV • Progesterone based preparations are not associated with thromboembolic risk • CV changes of pregnancy fully resolves after the sixth postpartum month • Repeat clinical assessment with ECHO (after 6m)  Baseline for future follow-up • Elective cardiovascular invasive procedures should be delayed until after the sixth postpartum month to avoid unnecessary thromboembolic risk • Functional deterioration - treated by • Restriction of activities and beta blockers (avoid atenolol) to reduce tachycardia and improve LV filling • Small dose of furosemide • Digoxin < BB (renal clearance of digoxin is increased during pregnancy) • Sustained or frequent palpitations –Needs prompt investigation • AF and other SVT  deleterious effect on uteroplacental perfusion • Prompt initiation of anticoagulation (potential teratogenicity and fetopathic effects of warfarin) • Rhythm control to prevent thromboembolic episodes and the risk of pulmonary edema • Elevated HR is crucial to maintain the augmented cardiac output in later pregnancy • Goal of ventricular rate control : 70-90 bpm • Electrical cardioversion • Poor response to rate control • Hemodynamic instability • Antiarrhythmic agent for maintenance of sinus rhythm -- The fetal safety profile to be considered • Most women with MS can undergo pregnancy without the need for invasive interventions • BMV : Severe symptoms or HF despite maximal medical therapy • Abdominal shielding should be employed • The procedure is best done past the period of organogenesis (>20 weeks) • Prior to mid to late third trimester • Gravid uterus can interfere with catheter access and hemostasis with the femoral approach

  22. MVP/MR in pregnancy Effect of pregnancy • MVP is well tolerated during pregnancy even when there is MR • Hypervolemia Increase in cardiac volume  Reduce valvular regurgitation • Decrease in SVR  Decrease in the regurgitant volume • Tachycardia increases forward stroke volume • Improve function of the prolapsed valve and obscure the physical findings of MVP • MVP with mild or moderate MR (During pregnancy and delivery) • Remain asymptomatic • Do not experience cardiac complications • Pregnancy tends to increase the frequency of atrial and ventricular premature beats - Beta blockers may be required

  23. MVP/MR in pregnancy • MVP with severe MR • Dyspnea, in particular after the second trimester (corresponds with the increase in CO) • CHF is rare • Occurrence of dyspnea/CHF does not carry a poor prognosis (Unlike in stenotic lesions) • Diuretics -- Chronic MR with pulmonary congestion • Preeclampsia (Increase in SVR and the decline in renal function)  Increases the risk of pulmonary congestion • Severe MR can be poorly tolerated during pregnancy only in three instances: • Acute MR resulting from chordal rupture • If AF occurs with a FVR • Long-standing severe MR complicated by severe LV dysfunction (prognosis being comparable to that of cardiomyopathy)

  24. MVP/MR in pregnancy • High risk candidates • NYHA class III to IV • LVEF < 40% • Severe PAH (PAP >75% of systemic pressure) • Should undergo mitral valve surgery/repair prior to pregnancy • Chronic MR with LAE  AF and atrial thrombi  Need for anticoagulation ; Attendant risks • Vaginal delivery can be performed in most women • Valve repair is the preferred procedure

  25. Other valvular lesions Aortic stenosis • BAV -- In developed countries • RHD Aortic regurgitation • Well tolerated during pregnancy • Normal fall in SVR improves the CO unless the regurgitation is severe Tricuspid regurgitation • Isolated acquired TR (endocarditis or carcinoid syndrome) -- well tolerated during pregnancy • The risk of diuretic-induced hypoperfusionmay be increased 

  26. Infective endocarditis Infective endocarditis prophylaxis Vaginal or cesarean delivery Not an indication for routine antibiotic prophylaxis Rate of bacteremia with these procedures is low Prophylaxis is not indicated for vaginal delivery or cesarean section (2007 AHA guidelines) Antibiotic prophylaxis is not recommended for genitourinary procedures (2008 AHA/ACC guidelines) IE prophylaxis is not recommended for vaginal or cesarean delivery in the absence of infection (ACOG, Committee on Obstetic Practice) • In patients with established infection that could cause bacteremia (chorioamnionitis or pyelonephritis) • The underlying infection should be treated in the usual fashion • Treatment should include an iv regimen effective for IE prophylaxis • Reasonable to consider IE prophylaxis before vaginal delivery at the time of membrane rupture in select patients with the highest risk of adverse outcomes (2008 ACC/AHA adult congenital heart disease guidelines) • Proof of efficacy of prophylaxis in this setting is not available • If antibiotic prophylaxis is given to prevent enterococcalendocarditis, amoxicillin, ampicillin and vancomycin are appropriate agents • Administered at the time of delivery • Rare and potentially life-threatening complication of pregnancy • Rates have not been well defined • In a 2003 review, 68 cases were identified • 18 of the cases (27%) occurred postpartum • Underlying heart disease – 31% • Recent dental work - 7% • IV drug use in 4% • Maternal mortality rate – 22% • Fetal mortality rate - 15% (Most of the data came from individual case reports and are subject to publication bias) Campuzano K et al. Bacterial endocarditis complicating pregnancy: case report and systematic review of the literature. Arch GynecolObstet 2003

  27. Acute coronary syndromes in pregnancy • Some studies have suggested an increased risk during pregnancy and in the early postpartum period Epidemiology — Two large epidemiologic studies: • California (1991 – 2000) --- Incidence of AMI: 2.8 per 100,000 deliveries Ladner HE et al. Acute myocardial infarction in pregnancy and the puerperium: a population-based study. ObstetGynecol 2005 • US (2000-2002) Nationwide Inpatient Sample of pregnancy discharges in about 1000 hospitals --- Incidence of 6.2 in 100,000 pregnancies James AH et al. Acute myocardial infarction in pregnancy: a United States population-based study. Circulation 2006 • The risk of MI was increased 3-4 times compared to nonpregnant women IHD -- Most common cardiac cause of maternal death -- Study from UK Roos-Hesselink JW, Duvekot JJ, Thorne SA. Pregnancy in high risk cardiac conditions. Heart 2009 Most cases occur in the third trimester and six-week postpartum period Roth A et al. Acute myocardial infarction associated with pregnancy. Ann Intern Med 1996 The infarction commonly involves the anterior wall Härtel D et al. [Myocardial infarction and thromboembolism during pregnancy]. Herz 2003 Is pregnancy itself a risk factor for MI? First-ever MI not related to pregnancy in women of child-bearing age -- 5.0 per 100,000 (3.6 million woman-years of observation) Petitti DB et al. Incidence of stroke and myocardial infarction in women of reproductive age. Stroke 1997

  28. ACS in pregnancy Risk factors — Four major risk factors for acute MI • Older maternal age (age >35 years) • Hypertension • Diabetes mellitus • Obesity US survey -- Multivariable regression model PREGNANCY COMPLICATIONS – Blood transfusions, post partum infections

  29. ACS in pregnancy Coronary artery morphology Coronary dissection Hormonal and hemodynamic changes  Structural changes in the intima and media of the arterial wall Dissection can occur in the absence of risk factors Hypertension  Independently damage the arterial wall -- more frequent dissections (HR for AMI 21) Spontaneous coronary artery dissection -- search for undiagnosed CTDs (such as EDS) Mather PJ et al. Postpartum multivessel coronary dissection. J Heart Lung Transplant 1994 Diagnosis and management Same principles as in the general population Troponins are preferred to CK-MB and troponin I may be the marker of choice in pregnant women US Survey (2000-2002): Cardiac catheterization was performed in 45% and PCI or CABG in 37% Evaluation of coronary morphology in 96 cases (1995-2005) by arteriography or autopsy Roth A et al. Acute myocardial infarction associated with pregnancy. J Am CollCardiol 2008

  30. ACS in pregnancyUnique considerations Labor and delivery • Induction of labor or scheduled cesarean delivery should be delayed (for at least 2-3 weeks) (No prospectivel clinical trials available) • Minimize the cardiac workload during delivery • Epidural anesthesia • Supplemental oxygen • Left lateral position • Treatment of HTN and tachycardia • Instrumental vaginal delivery or cesarean birth (in unstable cases) • Prior MI /PCI/CABG • Little information available • Thorough evaluation of their cardiac status, particularly LV function, ongoing myocardial ischemia and underlying coronary anatomy • Cessation of ACE inhibitors and statins The ESC guidelines • ECG and troponin level(s) should be performed in pregnant women with chest pain • Coronary angioplasty is the preferred reperfusion therapy for patients with STEMI • NSTEACS • Without risk criteria -- conservative strategy • With risk criteria -- invasive strategy ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011 • The fetus should be closely monitored with a plan for delivery if there is sudden maternal or fetal deterioration • In the event of maternal cardiac arrest, the best prognosis for the fetus occurs when delivery is within 4-5 minutes • Delivery may also aid maternal resuscitative efforts • Low dose aspirin (75 to 162 mg/day) appears to be safe in pregnancy • Clopidogrel : • Safety in human pregnancy has not been established (Animal studies – no teratogenic effects) • Clopidogrel + Aspirin : Might increase bleeding at the time of delivery • Fibrinolytic therapy – Relative contraindication • No controlled studies examining the efficacy and safety • No teratogenicity has not been reported • Risk of maternal hemorrhage : 8 % • The risk of puerperal hemorrhageis confined to women treated within eight hours of delivery (Stroke and massive pulmonary embolism have been treated safely during this period) • Anticoagulation • Heparin does not cross the placenta -- Does not affect the fetusdirectly • Bleeding complications in complicated pregnancy (eg, placenta previa, abruptio placenta) – Discontinue if bleeding occurs and during labour • PCI • BMS preferred • Safety of DES is unknown • Nitrates • Maternal hypotension should be avoided • Beta blockers • Generally safe   • Avoid atenolol • Labetalol may be the preferred beta blocker • ACE inhibitors, ARBs and statins--- Contraindicated • Outcome • MI in late third trimester  Highest risk for maternal death • - Increased cardiac demands during labor + Incomplete myocardial healing  Cardiac decompensation • In-hospital maternal mortality was 7.3% (Canada) and 5.1% (US)

  31. Cardiomyopathy in pregnancy • Ventricular dysfunction in childbearing women • Prior viral infection • HIV infection • Peripartumcardiomyopathy • Drug-induced cardiomyopathy (eg, cocaine, doxorubicin) • Women with LVEF < 40% • HF • Arrhythmias • Stroke were more common Siu SC et al. Risk and predictors for pregnancy-related complications in women with heart disease. Circulation 1997

  32. Cardiomyopathy in pregnancy Impact of etiology of the cardiomyopathy on outcomes • Study of 26 women from Brazil • Cardiac complications Idiopathic group >> PPCM with persistent LV dysfunction Avila WS et al. Pregnancy and peripartumcardiomyopathy. A comparative and prospective study. Arq Bras Cardiol 2002 • Study of 31 women from the US • Adverse maternal outcomes • Peripartum group >> Idiopathic group Bernstein PS et al. Cardiomyopathy in pregnancy: a retrospective study. Am J Perinatol 2001 • Study of 99 women with peripartumcardiomyopathy from Haiti • 15 had subsequent pregnancies • 50% of these women experienced worsening HF and long-term systolic dysfunction Fett JD et al. Brief communication: Outcomes of subsequent pregnancy after peripartumcardiomyopathy: a case series from Haiti. Ann Intern Med 2006

  33. Cardiomyopathy in pregnancy A study from Toronto evaluated rates of adverse maternal fetal and neonatal events in 36 pregnancies in women with DCM • 14/36 (39%) pregnancies were complicated by at least one maternal cardiac event • All maternal cardiac events occurred in women with either of • Moderate or severe LV dysfunction (LVEF <45%) • NYHA III or IV • Prior cardiac event Any one of these three risk factors  64% risk of an adverse cardiac event • The 16 month event-free survival • 18 pregnant women with LVEF <45% – 28% • 18 age and LVEF-matched nonpregnant women with DCM – 83% • Adverse fetal and/or neonatal event - 20% pregnancies Grewal J et al. Pregnancy outcomes in women with dilated cardiomyopathy. J Am CollCardiol 2009 Patients with known or suspected LV dysfunction should have an echocardiogram before conception, or as soon as possible after pregnancy is confirmed, to determine baseline ventricular function Pregnancy should be discouraged if EF <45%

  34. Peripartumcardiomyopathy Peripartumcardiomyopathy Epidemiology • Wide geographical variation • 1:2289 to 1:4000 live births in the US, 1:1000 in SA, 1:300 in Haiti and 1:100 in Nigeria Etiology • Still remains unknown and may be multifactorial • No distinct hormonal disorder has been identified Inflammatory cytokines • Elevated levels of TNF-alpha and IL-6 • Fas/Apo-1 and CRP are associated with more severe disease Sliwa K et al. Peripartumcardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J 2006 Pregnancy-associated cardiomyopathy Time of onset • Development of cardiomyopathy earlier in pregnancy Characteristics of early-onset disease • Review of 123 women with a H/o cardiomyopathy during pregnancy • 100 - PPCM • 23 - Earlier presentation (mean of 32 weeks) • No differences between the two groups • Age, race, associated conditions • LVEF (29 vs 27%), the rate and time of recovery • Maternal outcomes • Early presentation may be part of the spectrum of PPCM Elkayam U et al. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation 2005 Definition • Development of HF in the last month of pregnancy or ≤5 months of delivery • Absence of another identifiable cause for the HF • Absence of recognizable heart disease prior to the last month of pregnancy • LV systolic dysfunction (LVEF < 45% or a reduced fractional shortening) The last criterion was added to prevent the inclusion of patients with disorders that mimic systolic HF • Accelerated HTN, diastolic dysfunction, systemic infection, pulmonary embolism, or complications of late pregnancy itself (eg, preeclampsia or amniotic fluid embolus). Pearson GD et al. Peripartumcardiomyopathy: NHLBI and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000 Hibbard JU et al. A modified definition for peripartumcardiomyopathy and prognosis based on echocardiography. ObstetGynecol 1999

  35. Peripartumcardiomyopathy - Etiology Peripartumcardiomyopathy Risk factors Age > 30 years Multiparity African descent Pregnancy with multiple fetuses H/o preeclampsia, eclampsia or postpartum HTN Maternal cocaine abuse Long-term (>4 weeks) oral tocolytic therapy with beta agonists such as terbutaline Selenium deficiency : Conflicting data Abnormal immune response Maternal immunologic response to a fetal antigen Fetal cells may escape into the maternal circulation  Lodge in the cardiac tissue  Trigger a pathologic autoimmune response High titers of autoantibodies against cardiac tissue proteins (including myosin) (Ansari AA et al. Clin Rev Allergy Immunol 2002) No difference in the levels of serum immunoglobulins, between subjects and controls Cénac A et al. Absence of humoral autoimmunity in peripartumcardiomyopathy. A comparative study in Niger. Int J Cardiol 1990 Familial disease Evidence of familial clustering (Morales A et al Circulation 2010) Interaction between pregnancy related factors (eg, late pregnancy oxidative stress) and a susceptible genetic background • A retrospective review of 34 EMB specimens from PPCM patients • Incidence of myocarditis (9 %) • Comparable to that found in idiopathic DCM Rizeq MN et al. Incidence of myocarditis in peripartumcardiomyopathy. Am J Cardiol 1994 • Reasons for discrepancy • Small sample size • Time of biopsy • variability among patient populations • Limitations of EMB to diagnose myocarditis • Sampling error • Variability in histologic criteria Clinical presentation • Most common complaint: Dyspnea • Other frequent symptoms: • Cough, orthopnea, PND and hemoptysis • Nonspecific fatigue, chest discomfort or abdominal pain • Systemic and pulmonary emboli are more common PPCM >> Other cardiomyopathies • Risk is exacerbated by the hypercoagulable state induced by pregnancy Myocarditis A possible cause of PPCM? Sanderson et al. Peripartum heart disease: An endomyocardial biopsy study. Br Heart J 1986 • EMB in 5/11 (45%) pts with PPCM - Myocarditis • 6 months f/u : those with myocarditis had persistent HF • No or sparse evidence of myocarditis had improvement in HF symptoms and/or LV size and function • Two other series: • Myocarditis in 28% and 77% of patients with PPCM • Myocarditis in only 9% in idiopathic cardiomyopathy group O'Connell JB et al. Peripartumcardiomyopathy: clinical, hemodynamic, histologic and prognostic characteristics. J Am CollCardiol 1986 • Viral genomes were noted in 31% of PPCM with myocarditis Role of prolactin Altered prolactin processing Mice with a knockout in the STAT3 develop PPCM Reduction in STAT3  Increased cleavage of prolactin into an antiangiogenic and proapoptoticisoform

  36. Peripartumcardiomyopathy - Diagnosis Peripartumcardiomyopathy – Differential diagnosis Differential diagnosis • PPCM -- Diagnosis of exclusion • DDs: • Pre-existing idiopathic DCM unmasked by pregnancy • Pre-existing familial DCM unmasked by pregnancy • HIV/AIDS cardiomyopathy • Pre-existing valvular heart disease unmasked by pregnancy • Hypertensive heart disease • Pre-existing unrecognized CHD • Pregnancy-associated MI • Pulmonary embolus As mentioned in 2010 European Society of Cardiology (ESC) working group statement on peripartumcardiomyopathy BNP • PPCM pts typically have elevated BNP or NT-proBNP levels Chest x-ray • Cardiomegaly with e/o pulmonary venous congestion and/or interstitial edema (occasionally pleural effusions) • Not necessary to diagnose PPCM (exposes the patient to ionizing radiation) Cardiac magnetic resonance imaging • Limited reports; role is still being evaluated • Case reports and small series : Variable presence of LGE in patients with PPCM • The presence and persistence of LGE may be associated with poor recovery of cardiac function • Improving LGE may be associated with cardiac recovery • Lack of LGE may be associated with presence or absence of cardiac recovery • Prognostic value of CMR in PPCM has not been established Marmursztejn J et al. Delayed-enhanced cardiac magnetic resonance imaging features in peripartumcardiomyopathy. Int J Cardiol 2009 • Cardiac catheterization • Right heart catheterization is rarely needed • -Assessment of cardiac pressures can be made with Doppler echocardiography • May be helpful in critically ill patients • Endomyocardial biopsy • Role remains unclear • Variable proportion of pts have evidence of myocarditis • No pathognomonic findings in PPCM • Inherent risk in performing a biopsy of a dilated RV • Viral and bacterial studies • Role is unclear • Results nonspecific • Limited prognostic value in patients with myocarditis Electrocardiogram • Sinus tachycardia (rarely AF), nonspecific ST and T wave abnormalities and voltage abnormalities (low voltage or criteria for LVH) • Q waves are occasionally present in the anterior precordial leads • PR and QRS intervals may also be prolonged Echocardiography • Global reduction in contractility and LV enlargement without hypertrophy • LVEF <45% and/or fractional shortening <30%PLUS • LVESD > 2.7 cm/m2 (Based upon a 1992 NHLBI workshop definition for idiopathic DCM; Not precisely defined for PPCM) Other possible echocardiographic findings : • Regional heterogeneities of systolic wall thickening • LA enlargement • MR, TR • Small pericardial effusion

  37. Peripartumcardiomyopathy – Evaluation Measurement of BNP • Serial BNP levels may predict HF in at risk patients during pregnancy • BNP levels in healthy women increase two-fold during pregnancy (lower than that observed in HF) • A prospective study from Toronto evaluated BNP levels • 66 women with pregnancy and HD and 12 healthy women • Those with heart disease had significantly higher BNP levels (median 79 vs 35 pg/ml) • A BNP >100 pg/ml was measured in all 8 women with an adverse maternal cardiac event during pregnancy • In seven of these women the BNP >100 pg/ml was obtained prior to or at the time of decompensation Tanous D et al. B-type natriuretic peptide in pregnant women with heart disease. J Am CollCardiol 2010

  38. Peripartumcardiomyopathy - Treatment • Immunosuppressive agents • Efficacy is unclear: Occasionally initiated in patients with PPCM and biopsy-proven myocarditis • Empiric immunosuppression is not recommended • Significant side effects • Intravenous immune globulin • No clear evidence of benefit Bozkurt B et al. Intravenous immune globulin in the therapy of peripartumcardiomyopathy. J Am CollCardiol 1999 • Retrospective study of 6 women treated with IVIG and 11 controls treated conventionally • After 6m follow-up • Absolute increase in LVEF : IVIG group > controls (26 Vs 13%) Treatment • Largely similar to that for other types of HF • Additional therapeutic issues include anticoagulation and arrhythmia management • Immunosuppression and immune globulin therapy • Evaluated; Role is not established Arrhythmia management • AF occurs occasionally in patients with PPCM • Sustained VT has rarely been reported with PPCM Anticoagulation • High risk for thrombus formation and thromboembolism • Hypercoagulable state of pregnancy • Stasis of blood due to severe LV dysfunction • Use of anticoagulants should be considered particularly when there is severe LV dysfunction (LVEF <30 %)

  39. Peripartumcardiomyopathy – TreatmentBromocriptine • Heart transplantation • The only acceptable treatment if conventional therapy is not successful • Studies in early 90s : Transplantation was performed in up to one-third of cases • Transplantation was required in only 4 - 7 % (2005) • Success rates : Good • Long-term survival and frequency of transplant-associated complications (compared to matched idiopathic DCM) – Variable • Subsequent pregnancy has been cautiously undertaken after successful heart transplantation for PPCM • Bromocriptine • Beneficial response: Several case reports and one small randomized study • Available data are insufficient to recommend routine use of bromocriptine treatment for PPCM • The drug stops the production of breast milk making breastfeeding impossible • Insufficient evidence to establish the safety and efficacy • Larger trials are needed Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartumcardiomyopathy: a proof-of-concept pilot study. Circulation 2010 24 women (newly diagnosed PPCM) from S.Africa 10 10 (Bromocriptine+standard care) (standard care alone) (2.5 mg BD 2wks f/b 2.5 mg OD 6wks) At 6 months • LVEF 27 to 58% 27 to 36% • Mortality 1 4 • Composite of • Death 18 • NYHA III or IV • LVEF <35%

  40. Peripartumcardiomyopathy - management Delivery • Timing and mode of delivery: Limited data • multidisciplinary approaches are often useful • PPCM with advanced HF • Prompt delivery for maternal cardiovascular indications • Early delivery is not required if the maternal and fetal conditions are stable (The 2010 ESC working group statement) • Cesarean is generally reserved for obstetrical indications • Critically ill patients in need of inotropic therapy or mechanical support Breastfeeding • No clear data showing adverse cardiac effects from breast feeding • Breast feeding be avoided because of the potential effects of prolactinsubfragments (2010 ESC working group)

  41. Peripartumcardiomyopathy - prognosis Persistent LV dysfunction • The potential risks of subsequent pregnancy is substantial • During subsequent pregnancies • Mortality : 19% • Further reduction in the mean LVEF (36 to 32%) • HF symptoms : 7 patients • Premature delivery : 6 • Therapeutic abortion : 4 Elkayam U et al.NEngl J Med 2001 Fett JD et al. Brief communication: Outcomes of subsequent pregnancy after peripartumcardiomyopathy: a case series from Haiti. Ann Intern Med 2006 • Worsening HF : 53 % • 1 death from worsening HF 10 months postpartum • Seven women did not develop worsening HF (All had continued improvement and normalization of LV function (LVEF ≥50 %) within 30 months of the subsequent pregnancy) • Although some women tolerate further pregnancies, those with persistent LV dysfunction should be advised to  avoid pregnancy due to the risk of HF progression and death Findings in other reports • Mortality rate : 6 % at 5 years (Felker GM N Engl J Med 2000) 23% (13/57) (Witlin AG Am J ObstetGynecol 1997; Sliwa K J Am CollCardiol 2000) • Transplant rate : 7% at 8.6 years (Felker GM et al. Am Heart J 2000) • Death due to PPCM is usually caused by • Progressive pump failure • Sudden death • Thromboembolic events • Adverse prognostic factors • Worse NYHA functional class • Black women • Multiparity Recovered LV function • Risk of subsequent pregnancy • Recovered LV function << Persistent LV dysfunction • But elevated compared to the general population • Series of 28 women (recovered to an LVEF ≥50%) during subsequent pregnancy • No deaths • Reduction in the mean LVEF (56 to 49%) • LVEF fell by more than 20% in six women (21%) • HF symptoms : 6 patients • The persistent risk may be related to subtle residual dysfunction not detected on resting evaluations Elkayam U et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartumcardiomyopathy. N Engl J Med 2001 Obstetric and neonatal outcome • Data are more limited • In the above report of 123 patients • Cesarean delivery : 40% (largely for obstetric indications) • Preterm birth (<37 weeks) occurred in 25% • Mean birth weight was 3.1 kg (range 1.4 to 5.0 kg), • Small for date: 5.9 % • Two stillbirths; one neonatal death and four had congenital anomalies Subsequent pregnancy • The risks -- Incompletely defined • Several small case series suggest high complication rate (Especially who do not have full recovery of LV function) • Subtle residual dysfunction matters? • Report of seven women with h/o PPCM who regained normal resting LV size and performance • Contractile reserve (assessed by dobutamine challenge) was significantly impaired compared to matched controls Lampert MB et al. Contractile reserve in patients with peripartumcardiomyopathy and recovered left ventricular function. Am J ObstetGynecol 1997 • In summary, some women who recover LV function after an initial episode of PPCM will have significant decline in LV function during a subsequent pregnancy • These women should be counseled about the potential risks prior to pregnancy • Carefully monitored for signs of ventricular dysfunction if they choose to become pregnant again Outcomes in cardiomyopathy is related to etiology • Predictors of persistent LV dysfunction at follow-up: • LVEF ≤30 % • Fractional shortening <20 % • LVEDD ≥6 cm • Elevated cardiac troponin T • Baseline LVEF has limited sensitivity for prediction of improvement in individual patients • Severely depressed baseline LVEF – Not an indication for premature use of aggressive therapies (VAD and cardiac transplantation) • PPCM is associated with significant extracardiac morbidity • Study of 182 women • One-third of patients with transplantation-free survival had residual brain damage as a result of CVA or cardiopulmonary arrest Goland S et al. Clinical profile and predictors of complications in peripartumcardiomyopathy. J Card Fail 2009 Prognosis Maternal outcome • The largest series of 123 cases of PPCM • Cardiac transplantation rate : 4% • Mortality rate : 10 % (mean follow-up of 2 yrs) • ICD – 3% • PPI – 2% • Among who did not die or require transplantation • Mean LVEF increased from 28% at diagnosis to 46 % • Recovery to an LVEF > 50% occurred in 54% of patients • Degree of recovery was greatest in those with a baseline LVEF >30% • Almost all of the recovery of LV function occurred by 6 months after diagnosis Elkayam U et al. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation 2005 Following heart transplantation • Only anecdotal reports of successful pregnancy in patients post transplantation for PPCM • In addition to the problems related to pregnancy after heart transplantation • May be at risk for graft failure due to recurrent disease • These women should be strongly advised to avoid future pregnancy

  42. Risks of prosthetic valves in pregnancy • Variety of complications • Structural failure of the valve, Infection, HF, Thromboembolism and bleeding due to anticoagulation • Overall incidence of complications in appropriately managed, nonpregnant patients with prosthetic valves is ̴3 %/yr • Mechanical heart valves  Increased incidence of thromboembolic events during pregnancy • Therapeutic anticoagulation throughout pregnancy is essential • Absence of adequate prospective controlled trials -- preferred anticoagulant regimen is uncertain Bioprosthetic valves : Do not require anticoagulation, independent of position (unless there are other thromboembolic risk factors) Significantly higher incidence of valve failure than mechanical valves Particular concern for young women

  43. Bioprosthetic valves in pregnancy North RA et al. Long-term survival and valve-related complications in young women with cardiac valve replacements. Circulation 1999 • Evaluation of the risk of pregnancy • Natural history study of 232 young women with prosthetic valves • 55 to 60 % in each of these groups had at least one pregnancy • 73 had a bioprosthesis and 72 a homograft • Structural valve deterioration and valve loss: More common with bioprosthetic valves • The 10 year rate of valve loss (valve replacement or valve-related death) • bioprosthetic : 82% • homografts : 28 % • The risk of valve deterioration: mitral >> aortic or tricuspid site (Seven fold) • 10 year patient survival: • bioprosthetic : 84% • homograft valves : 96% • The rate of valve loss was not higher for those who had completed a pregnancy • Similar findings Jamieson WR et al. Pregnancy and bioprostheses: influence on structural valve deterioration. Ann ThoracSurg 1995 • 237 women ≤35 years of age with bioprostheses • 52 of the women had 94 pregnancies • At 10 years • structural valve deterioration : 55 vs 46% • valve-related mortality : 8 vs 7 % • Pregnancy group did not have a significantly higher rate of events • Durability of pulmonary autografts in pregnant women • Limited data • No evidence of valve deterioration in two reports of 55 pregnancies in 29 women Structural failure of bioprosthetic valves • 30 -35% of heterograft and 10 - 20% of homograft prostheses fail within 10 -15 years of implantation • Leaflet degeneration  Severe regurgitation • Progressive valve calcification  Significant stenosis • Does pregnancy accelerate deterioration of bioprosthetic valves? • Initial studies: YesVongpatanasin W et al. Prosthetic heart valves. N Engl J Med 1996Sbarouni E et al. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994 • Recent studies : No Avila WS et al. Influence of pregnancy after bioprosthetic valve replacement in young women: a prospective five-year study. J Heart Valve Dis 2002

  44. Prosthetic valves – pregnacy care Delivery • Whenever possible, delivery should be planned • Modality should be discussed with the obstetricians, hematologists and anesthetists • Vaginal delivery is preferred in most cases • Cesarean delivery should be reserved • Specific obstetrical indications • Significant cardiovascular disease that places the woman at additional risk during labor Prior to conception • Preconception counseling • Informed discussion about the maternal and fetal risks associated with available anticoagulation options • Risk of life threatening thromboembolic events and a thrombotic stroke exists regardless of the anticoagulant regimen utilized • Continue oral anticoagulation until pregnant (Risk of warfarinembryopathy is low in the first 6 weeks of gestation) • Prompt pregnancy test if menses are delayed

  45. Prosthetic valve thrombosis during pregnancy  • Valve thrombosis -- a life-threatening complication • The procoagulant state of pregnancy increases the risk • Depends upon the type and location of the prosthetic valve • Mechanical valves >> Bioprosthetic valves or homografts • Older mechanical valves >> Newer generation mechanical valves • Mitral position Other factors • H/o prior thromboembolic event • AF • Multiple prosthetic valves • Risk appears to be increased with UFH and LMWH (lesser degree) compared to warfarin

  46. Prosthetic valve thrombosis during pregnancy  • Experience is limited • Controlled data do not exist • Published reports are mostly from case series • Heparin may be considered for small, nonobstructive thrombi • For obstructive valve thrombosis, the treatment options are surgical thrombectomy and thrombolysis • No direct comparisons between surgery and thrombolysis exist

  47. Management of valve thrombosis during pregnancy  • Both surgery and thrombolysis carry substantial fetal and maternal risks • Series of 10 women treated for 12 episodes of valve thrombosis • Surgery (4 cases) • Thrombolysis (7 cases) • Heparin (1 case) Sahnoun-Trabelsi I et al. [Prosthetic valve thrombosis in pregnancy. A single-center study of 12 cases]. Arch Mal Coeur Vaiss 2004

  48. Cardiac surgery and thrombolysis during pregnancy • Weiss BM et al. Outcome of cardiovascular surgery and pregnancy: a systematic review of the period 1984-1996. Am J ObstetGynecol 1998 • Review of cardiac surgery during pregnancy • 70 patients • Perioperative maternal mortality – 6% • Fetal mortality - 30% • Turrentine MA et al. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. ObstetGynecolSurv 1995 • Review of thrombolysis during pregnancy • 172 patients • Maternal mortality – 1.2% • Hemorrhagic complications – 8% • Fetal mortality - 5.8% • Both of these series included patients treated for a variety of conditions at a number of centers over an extended period of time (12 years for the surgical series and 34 years for thrombolysis)

  49. Pregnancy after cardiac transplantation Preconception care • Preconception counseling • Reason for the mother's cardiac transplant • Risk of recurrence in mother (PPCM) or offspring (CHD) • Timing of pregnancy • Avoid during the first year post transplantation • Risk of rejection is greatest • Immunosuppressive therapy - Most aggressive • Contraception during this period is important (fertility is not affected by medications) The AST consensus conference recommedations for timing of pregnancy: • No rejection in the past year • Adequate and stable graft function • No acute infections that might impact the fetus • Maintenance immunosuppression at stable dosing • A multidisciplinary care team should be available throughout pregnancy and the postpartum period • Escalating number of female heart transplant recipients of childbearing age • Overall increase in heart transplantation in adults • Aging pediatric heart transplant population • 1988 - First report of pregnancy after heart transplantation • Pregnancy - generally been discouraged by most heart transplantation centers • Potential risks to the prospective mother • Possible teratogenic effects from immunosuppressive drugs

  50. Maternal physiology and the heart transplant recipient

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