Implantation Most pacemakers are implanted transvenously using the cephalic or sub- clavian vein. An incision is made about 2 cm below the clavicle across the deltopectoral groove. T he cephalic vein is isolated and is often of suf \201 cient caliber to accept two pacing w ires. Alternatively, a guide wire can be introduced followed by introducer sheaths to provide acc ess. Sometimes the cephalic vein is not suitable and the leads have to be introduced via pu ncture of the subclavian vein using the Seldinger technique. The ventricular lead is most c ommonly placed in the RV apex. RV out \202 ow tract or on the septum, an active \201 xat ion lead is required. The atrial lead is placed in the right atrial appendage ideally, but any- where in the RA w ith adequate pacing parameters is acceptable although likely to require an active \201 xa tion lead (Table 9.6). After both leads are placed in acceptable positions, they are then secured and attached to the pulse generator, which is placed either subcu- taneously or beneath the pectoral muscle s. Indications for permanent pacing are listed in Box 9.8. Table 9.6 Acceptable pacing parameters for new leads Atrium Ventricle Threshold* <1.5 V <1.0 V Sensitivity >1.5 mV >4.0 mV Slew rate >0.2 V/sec >0.5 V/sec Impedance 400 \200\2231000 ohms 400 \200\2231000 ohms Using a pulse width of 0.5 ms. PERMANENT PACEMAKERS 399 Box 9.8 Indications for permanent pacing De \201 nite indications \200 Symptomatic third-degree heart block \200 \200 \200 Symptomatic advanced second-degre e heart block Third-degree or advanced second-degree heart block in patients with atrial \201 brillation and bradycardia with pauses of >5 seconds Advanced second-degree heart bloc k with pauses Bifasicular block with intermittent third-degree, second-degree block or alte rnating bundle branch block Trifasicular block with intermittent third-degree or second-deg ree block After STEMI in the presence of persistent high-grade AV block Symptomatic sinus n ode dysfunction Symptomatic chronotropic incompetence Carotid sinus hypersentivity with rec urrent syncope Sustained VT caused by pauses Conditions requiring drugs that result in symp tomatic bradycardia Bradycardia with symptoms Pauses (cid:116)3 seconds Awake ventricular rates <40 bpm \200 \200 (cid:116)3 seconds \200 \200 \200 \200 \200 Relative indications \200 Asymptomatic third degree block with V rate <40 or second degree (type II) with distal hear t block Sinus node dysfunction (SND) with HR <40 and where symptom \200\223 ECG correlation is not available Syncope and SND evident on EPS High-risk patients with long QT syndrome C hronic chronotropic incompetence (HR <40) Neurocardiogenic syncope with signi \201 cant br adycardia on tilt testing Symptomatic HCM with out \202 ow gradient \200 \200 \200 \200 Adapted from ACC/AHA/ \200\231NASPE 2008 Guidelines. J Am Coll Cardiol 2008; 51(21):2085 \200\2232105. CHAPTER 9 Arrhythmias 400 Which pacing modality? The vast majority of patients should have atrial-based pacing (i.e., either AAI or DDD) (see Fig. 9.12). Ventricular-only pacing leads to a greater incidence o f AF and potential pacemaker syndrome. Bradycardic Patient No P waves VVI(R) Permanent AF Yes Sinus bradycardia - Sick sinus syndrome (SSS) No Consider AAI(R) AV conduction abnormal? No Yes 2nd & 3rd degree HB - Bi & trifasicular block - Carotid sinus syncope No DDD(R) LBBB and poor LV function? Yes Biventricular Pacing Figure 9.12 Algorithm to select the optimal pacing mode. COMPLICATIONS OF PACING 401 Complications of pacing Pacemaker syndrome This occurs in patients with intact VA conductio n during VVI pacing. Symptoms include presyncope, syncope, lightheadedness, fatigue, exerci se intolerance, malaise, lethargy, dyspnea, headache, chest pain, and nonspe- ci \201 c sy mptoms. Loss of AV synchrony can decrease cardiac output by 20% at rest. There is atrial contractio n against a closed mitral and tricuspid valve, leading to cannon waves. There is also activ ation of atrial stretch receptors with release of atrial natriuretic peptide (ANP). The treatment is to restore AV synchrony by either reducing the pacing rate or inserting an atrial lead. Endless loop tachycardia (pacemaker-mediated tachycardia [PMT]) This occurs in dual-chamber pacing (VDD, DDD, or DDDR) and is caused by inappropriate sensing of retrograde P waves, w hich trigger a ventricular response. The treatment is to increase the postventricular atria l refractory period (PVARP) to prevent sensing of the retrograde P wave or activate a varie ty of anti-PMT algorithms. Other tachycardias Atrial \202 utter or \201 brillation can cause rapid ventricular pac ing in dual-cham- ber systems by sensing and tracking the atrial rate. To overcome this, th e pacemaker can either mode-switch to VVI or be reprogrammed to DDI so that the atrial rate cannot be tracked. Interference MRI is generally contraindicated in a patient with a pacemaker, as it can cause serious mal function. However, recommendations are changing and MRI-compatible systems are being develo ped. Radiation therapy can damage pacemaker electronics or result in erosion of the generator. T he radiation dose is cumulative. Shielding is mandatory. The pulse generator should be inte rrogated after therapy and may need to be replaced. Cautery pacemaker needs to be checked before and after surgery as the electronics of the ge nerator can be damaged. It should be reprogrammed to a non-sensing mode (VOO) prior to surg ery or have a magnet applied during cautery to force the device to pace (see below). CHAPTER 9 Arrhythmias 402 Magnet response When the pacemaker is within a suf \201 ciently strong magnetic \201 eld , it reverts to its magnet mode. This is non-sensing \201 xed pacing at the device \200 \231s \200\234magnet rate \200\235 usually 70 \200\22380 /min, i.e., DOO (dual chamber) or VOO/ AOO (single chamber). Additional potential complications of pacing include lead malfunction, device recalls, and device infection. Evaluation and management of these problems should be done in consultatio n with a cardiovascular specialist. Pacemaker follow-up The device is interrogated every 6 \200\22312 months. The battery volta ge is measured, and below a critical level the elective replacement indicator (ERI) activat es. There are approximately 6 months between ERI and the dangerous EOL (end of life). The lead(s) function is assessed by checking pacing threshold, sensitivity (the size of sen sed electrogram detected), and pacing impedance. Any change in these parameters could indic ate a problem, e.g., low impedance suggests an internal insulation break, while high impeda nce might suggest a conductor problem. Modern devices store the time and duration of many changes of pace- maker function, which i s helpful for arrhythmia detection. Most can also store electrograms that help in the diagn osis of arrhythmias and pace- maker malfunction. Remote or transtelephonic monitoring may also aid in careful patient follow-up. PACEMAKERS FOR CHRONIC HEART FAILURE 403 Pacemakers for chronic heart failure Cardiac resynchronization therapy (CRT) CRT is a novel treatment for symptomatic heart failure (NYHA Class III \200\223IV). In patients with a ve ntricular conduction delay, coordination of wall motion in the left ventricle can be improv ed by pacing the lateral LV (via the coronary sinus) and septum (via the RV) simultaneously . This improves cardiac output and symptoms. Ventricular \201 lling may be improved by op ti- mizing the AV delay. Current indications \200 \200 \200 \200 \200 \200 NYHA Class III \200\223IV heart failure On optimal medical therapy Sinus rhythm QRS duratio n >120 ms LVEF LVEDD (cid:100)35% (cid:116)55 mm Electrical vs. mechanical dyssynchrony Looking at QRS width on a 12 lead ECG is simple and widely available but is a very crude tool for assessing mechanical dyssynchrony and may exp lain why as many as 30% of patients in clinical trials have not responded to CRT. However, LBBB is more prevalent in CHF and associated with increased mortality. Mechanical dyssynchrony consists of the following: Atrioventricular dyssynchrony Interventr icular dyssynchrony (delay between RV and LV contraction) Intraventricular dyssynchrony (di fferences in regional wall motion) \200 \200 There are various ways to assess mechanical dyssynchrony, including the 12 lead ECG, cardia c MRI, radionuclide ventriculography, and echocar- diography, which is probably the most us eful because of its availability and simplicity. Interventricular dyssynchrony can be measu red by the diffe- rence in the aortic and pulmonary pre-ejection times (measured from the b eginning of the QRS to aortic or pulmonary valve opening). A signi \201 cant difference is 40 ms. Intraventricular dyssynchrony can be assessed using tissue Doppler imaging (TDI), looking a t the time to peak systolic contraction in different segments of the LV, in particular the difference between the septum and the lateral wall. Strain rate in different segments and c olor TDI can reveal signi \201 cant intraventricular dyssynchrony. Implantation The RA and RV leads are inserted by conventional techniques as described earli er. The coronary sinus (CS) is the preferred route for pacing the left ventricle (see Fig. 9.13). Normally, a venogram of the CS is performed using an occlusive balloon and a suitabl e lateral or posterolateral vein identi \201 ed. The unipolar or bipolar LV lead is then i nserted either with a stylet or using an over-the-wire (OTW) technique into a stable positi on with acceptable pacing parameters and no diaphragmatic stimulation. CHAPTER 9 Arrhythmias 404 With increasing evidence for the prevention of sudden cardiac death in patients with heart failure, most biventricular pacemakers will include a de \201 brillator. A thorascopic app roach to LV lead placement has also been used. Future directions There is evidence of mechanical dyssynchrony in some patients with heart failure and a narrow QRS who may bene \201 t from CRT. Patients who have had AV nodal ablation for symptomatic AF have bet- ter exercise tolerance with biventricular pacing than with RV pacing alone. Pacing the apex of the RV is not the optimal site for ventricular function, and high septal or His pacing may improve hemodynami cs. Figure 9.13 Location of the coronary sinus (CS) prior to placing a left ventricular lead. S hown is a \202 uoroscopic image of the heart from the RAO projection. There is an active \201 xation lead in the conventional right atrial appendage (RAA) and a lead in the right ventricular apex. Dye has been injected from below retrogradely up the CS to demonstrate t he lateral left ventricular branches, from where pacing stimuli can capture the ventricle. 405 Chapter 10 Heart disease in pregnancy Basic principles 406 Physiological changes in pregnancy 407 Normal \201 ndings in pregnan cy 409 General considerations in pregnancy 410 Pulmonary hypertension and pregnancy 411 Mar fan \200\231s syndrome and pregnancy 413 Valvular heart disease in pregnancy 414 Mitral ste nosis and pregnancy 415 Other valve lesions 416 Mechanical heart valves in pregnancy 417 Is chemic heart disease 419 Hypertrophic obstructive cardiomyopathy (HOCM) 420 Peripartum card iomyopathy 421 Arrhythmias in pregnancy 423 Cardiac arrest in pregnancy 424 Endocarditis pr ophylaxis 425 CHAPTER 10 Heart disease in pregnancy 406 Basic principles Cardiac disease in pregnancy is rare in the United States, Europe, and the developed world, but it is common in developing countries. In the United States, rheumatic heart disease is now extremely rare in women of childbearing age. Women with congenital heart disease who have undergone corrective or palliative surgery in childhood and survive into adulthood are encoun- tered more frequently. These women may hav e complicated pregnancies. Women with mechanical prosthetic valves face dif \201 cult deci sions regard- ing anticoagulation during pregnancy. Ischemic heart disease is becoming more common in pregnancy as the mean age of pregnancy in creases and the smoking epidemic continues. Dissection of the aorta and its branches occurs more commonly in preg- nancy and postpartum. Pregnancy may cause a speci \201 c dilated c ardiomy- opathy \200\224peripartum cardiomyopathy. Because of signi \201 cant physiological changes in pregnancy, symptoms such as palpitatio ns and signs such as an ejection systolic murmur are very common and innocent \201 ndings . The care of the pregnant and parturient woman with heart disease requires a multidisciplina ry approach and formulation of an agreed-on and documented management plan encompassing man agement of both planned and emergency delivery. This chapter covers the most important cardiac conditions relevant to pregnancy. PHYSIOLOGICAL CHANGES IN PREGNANCY 407 Physiological changes in pregnancy Cardiac output increases early in pregnancy, reaching a maximum by the mid second trimester and plateaus at 30% \200\22350% above pre-pregnancy lev - els. This is achieved by an increase in both stoke volume, as a result of increased blood volume, and heart rate (Table 10.1). There is peripheral vasodilation and a fall in systemic and pulmonary vascular resistance ( Fig. 10.1). The pregnant uterus can require up to 18% of cardiac output. Oxygen consumption increases throughout pregnancy and reaches 30% above pre-pregnancy levels by the time of d elivery. Although there is no increase in pulmonary capillary wedge pressure (PCWP), serum colloid o ncotic pressure is reduced. The colloid oncotic pressure \200\223pulmonary capillary wedge pressure gradient is reduced by 28%, making pregnant women particularly susceptible to pulm onary edema. Pulmonary edema will be precipitated if there is either an increase in car- di ac preload (such as infusion of \202 uids) or increased pulmonary capillary permeability (such as in pre-eclampsia), or both. In late pregnancy in the supine position, pressure of the gravid uterus on the inferior ven a cava causes a reduction in venous return to the heart and a consequent fall in stroke vol ume and cardiac output. Turning from the lateral to the supine position may result in a 25% reduction in cardiac output. Pregnant women should therefore be nursed in the left or righ t lateral position whenever possible. If the mother has to be kept on her back, the pelvis should be rotated so that the uterus drops forward, and cardiac output and uteroplacental b lood \202 ow are optimized. Reduced car- diac output is associated with reduction in uter ine blood \202 ow and thus in placental perfusion; this can compromise the fetus. Labor is associated with further increases in cardiac output (15% in the \201 rst stage a nd 50% in the second stage). Uterine contractions lead to autotransfusion of 300 \200\22350 0 mL of blood back into the circulation. The sympathetic response to pain and anxiety furth er elevate heart rate and blood pressure. Cardiac output is increased more during contracti ons than between contractions. Following delivery, there is an immediate rise in cardiac output due to the relief of infer ior vena cava obstruction and contraction of the uterus that empties blood into the systemi c circulation. Cardiac output increases by 60% \200\22380% followed by a rapid decline to p re-labor values within about 1 hour of delivery. Peripheral vascular resistance also rises. Transfer of \202 uid from the extravascular space increases venous return and stroke volu me further. Those women with cardiovascular compro- mise are therefore most at risk for pul monary edema during the second stage of labor and the immediate postpartum period. CHAPTER 10 Heart disease in pregnancy 408 Table 10.1 Physiological changes in cardiovascular system in pregnancy Cardiac output i 40% i Stroke volume i Heart rate 10 \200\22320 beats/min d Blood pressure First and second trimester l Third trimester l Central venous pressure l Pulmonary capillary wedge pressure (PCWP) d Systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) 25% \200\22330% d Serum colloid osmotic pressure 10% \200\22315% ) n m i ) l ) l m m / I ( ) m p b ( ( ( t u p t u o c a d r a C 8 e m u o v e m u o v l e t a r l a m s a l P e k o r t S t r a e H 90 i 3750 90 Plasma volume 3500 3250 80 6 3000 80 70 2750 Heart rate Cardiac output and stroke volume 2500 2250 70 60 4 Non- pregnant 24 28 32 36 4 8 12 16 20 Post- delivery Gestation (weeks) Figure 10.1 Physiological changes in pregnancy. Systemic and pulmonary vascular resistance fall during pregnancy. Blood pressure may fall in the second trimester, rising slightly in late pregnancy. Note that the cardiac output and stroke volume peak by 16 weeks gestation. Reprinted with permission from Throne SA (2004). Heart 90(4):450 \200\223456. NORMAL FINDINGS IN PREGNANCY 409 Normal \201 ndings in pregnancy On examination Findings may include the following: \200 \200 Bounding/collapsing pulse. Prominent a- and v-waves Ejection systolic murmur (present in ov er 90% pregnant women. May be quite loud, and audible all over the precordium) Third heart sound Relative sinus tachycardia Atrial and ventricular ectopy Peripheral edema Bibasilar r ales \200 \200 \200 \200 On ECG These \201 ndings are partly related to changes in the position of the heart: \200 \200 \200 \200 Atrial and ventricular ectopy Q wave (small) and inverted T wave in lead III ST-segment dep ression and T-wave inversion inferior and lateral leads. QRS-axis leftward shift Investigations \200 The amount of radiation received by the fetus during a maternal CXR is negligible and CXRs should never be withheld if clinically indicated in pregnancy. The fetus should be shielded . Transthoracic (TTE) and transesophageal (TEE) echocardiograms are also safe with the usua l precautions to avoid aspiration. MRIs are safe in pregnancy. Routine investigation with e lectrophysiological studies and angiography are normally postponed until after pregnancy bu t should not be withheld in, e.g., acute coronary syndromes. \200 CHAPTER 10 Heart disease in pregnancy 410 General considerations in pregnancy The heart has relatively less reserve than that of the respiratory system. Women with heart disease may not be able to increase their cardiac out- put adequately to cope with pregnancy and delivery. The outcome and safety of pregnancy are related to the following: Presence and severity of pulmonary hypertension Presence of cyanosis Hemodynamic signi \201 cance of the lesion (MR and AI are well tolerated whereas AS and MS are more likely to cause problems) Functional class as determined by the level of activity that leads to dyspnea (New York Heart Associat ion [NYHA])1 \200 \200 Cardiac events such as stroke, arrhythmia, pulmonary edema, and death complicating pregnanc ies are predicted by the following2: \200 \200 \200 \200 \200 A prior cardiac event or arrhythmia NYHA classi \201 cation >II Cyanosis Left ventricular ejection fraction <40% Left heart obstruction (mitral valve area <2 cm cm2, aortic valve gr adient >30 mmHg) 2, aortic valve area <1.5 Women with congenital heart disease are at increased risk of having a baby with congenital heart disease and should therefore be offered detailed scanning for fetal cardiac anomalies . Women with cyanosis (oxygen saturation <80% \200\22385%) have an increased risk of intraute rine growth restriction, fetal loss, and thromboembolism secondary to the reactive polycyth emia. Their chance of a livebirth in one study was <20%.3,4 In addition, there is a signi \201 cant mortality risk to the mother. Women with the above risk factors for adverse cardiac or obstetric events should be managed and counseled by a multidisciplinary team including cardiologists with expertise in pregna ncy, obstetricians, fetal medicine specialists, and pediatricians. Regular antenatal visits and judicious monitoring to avoid or treat expe- diently any anemi a or infection or cardiac decompensation are essential. There should be early involvement o f obstetric anesthesiologists and a carefully documented plan for delivery. 1 McCaffrey FM, Sherman FS (1995). Pregnancy and congenital heart disease: the Magee Women \200\231s Hospital. J Matern Fetal Med 4:152 \200\223159. 2 Siu SC, Sermer M, Colman, et al . (2001). Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 104:515 \200\223521. 3 Presbitero P, Somerville J, Stone S, et al. (1994). Preg nancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation 89:267 3 \200\2232676. 4 Weiss, BM, Zemp L, Seifert B, Hess OM (1998). Outcome of pulmonary vascul ar disease in preg- nancy. J Am Coll Cardiol 31:1650 \200\2231657. PULMONARY HYPERTENSION AND PREGNANCY 411 Pulmonary hypertension and pregnancy Pulmonary vascular disease, whether secondary to a rev ersed large left-to- right shunt such as a VSD (Eisenmenger \200\231s syndrome) or lung or connective tissue disease (e.g., scleroderma) or due to primary pulmonary hyperten- sion, i s extremely dangerous in pregnancy. Women known to have pulmonary vascular disease should be advised from an early age to avoid pregnancy and be given appropriate contracep- tive advice. Maternal mortality is 40%.1 The danger relates to \201 xed pul- monary vascular resistance (PVR) and an inability to inc rease pulmonary blood \202 ow with refractory hypoxemia. Most deaths can be attributed to thromboembolism, hypovolemia, or pre-eclampsia. Pulmonary hypertension is de \201 ned as a nonpregnant elevation of mean (not systolic) pu lmonary artery pressure (cid:116)25 mmHg at rest or 30 mmHg on exercise in the absence of a left-to-right shunt. Pulmonary artery sys- tolic (not mean) pressure is usually estimated by using Doppler ultrasound to measure the regurgitant jet velocity across the tricuspid va lve. This should be considered a screening test. There is no agreed-upon relation between the mean pulmonary pres- sure and the estimated sy stolic pulmonary pressure. If the systolic pul- monary pressure estimated by Doppler is tho ught to indicate pulmonary hypertension, a specialist cardiac opinion is recommended. If th ere is pul- monary hypertension in the presence of a left-to-right shunt, the diagnosis of pulmonary vascular disease is particularly dif \201 cult and further investi- gation inclu ding cardiac catheterization to calculate pulmonary vascular resistance is likely to be nec essary. Pulmonary hypertension as de \201 ned by Doppler studies may also occur in mitral stenosis and with large left-to-right shunts that have not reversed. Although such women may not ha ve pulmonary vascular disease and a \201 xed PVR (or this may not have been established p rior to pregnancy), they have the potential to develop it and require very careful monitori ng with serial echocardiograms. Management \200 In the event of unplanned pregnancy, a therapeutic termination should be offered.1 Elective termination carries a 7% risk of mortality, hence the importance of avoiding pregnancy if possible. If such advice is declined, multidisciplinary care, elective admission for bed re st, oxygen, and thromboprophylaxis are recommended.2 There is no evidence that monitoring t he pulmonary artery pressure pre- or intrapartum improves outcome. Indeed, insertion of a p ulmonary artery catheter increases the risk of thrombosis, which may be fatal in such women .3 1 Yentis SM, Steer PJ, Plaat F (1998). Eisenmenger \200\231s syndrome in pregnancy: materna l and fetal mortality in the 1990s. Br J Obstet Gynaecol 105:921 \200\223922. 2 Avila WS, G rinberg M, Snitcowsky, et al. (1995). R. Maternal and fetal outcome in pregnant women with Eisenmenger \200\231s syndrome. Eur Heart J 16:460 \200\223464. 3 Rosenthal E, Nelson-Pierc y C (2000). Value of inhaled nitric oxide in Eisenmenger syndrome during pregnancy (letter) . Am J Obstet Gynecol 183:781 \200\223782. CHAPTER 10 Heart disease in pregnancy 412 Vasodilators given to reduce the pulmonary artery pressure will (with the exception of inha led nitric oxide and prostacyclin), inevitably result in a concomitant lowering of the syst emic pressure, exacerbating hypoxemia and affecting fetal perfusion. There is no evidence t hat abdominal or vaginal delivery or regional vs. general anesthesia improves outcome in pr egnant women with pulmonary hypertension. Maternal mortality is extremely high whatever mea sures are taken. Most fatalities occur during delivery or the \201 rst week postpartum. MARFAN \200\231S SYNDROME AND PREGNANCY 413 Marfan \200\231s syndrome and pregnancy Eighty percent of Marfan patients have some cardiac involvement, most commonly mitral valve prolapse and regurgitation. Pregnancy increases th e risk of aortic rupture or dissection, usually in the third trimester or early postpartum. The adverse affects of hormonal and physiologic changes on the abnor- mal aorta result in a n unpredictable maternal risk of aortic dissection or rupture. Progressive aortic root dila tion and an aortic root dimension >4 cm are associated with increased risk (10%). Those wit h aortic roots >4.6 cm should be advised to delay pregnancy until after aortic root repair. 1 Conversely, in women with minimal cardiac involvement and an aortic root <4 cm, pregnancy o utcome is usually good,2 although those with a family history of aortic dissection or sudde n death are also at increased risk. Genetic counseling is vital prior to pregnancy. Management \200 B \200 \200 Monthly echocardiograms if documented aortopathy Blockers for those with hypertension or aortic root dilation Vaginal delivery for those wit h stable aortic root measurements but elective cesarean section with regional anesthesia if there is an enlarged or dilating aortic root* Associated with neonatal complications (prematurity, respiratory distress, IUGR, intraventr icular hemorrhage, death). 1 Lipscomb KJ, Clayton Smith J, Clarke B, et al. (1997). Outcome of pregnancy in women with Marfan \200\231s syndrome. Br J Obstet Gynaecol 104:201 \200 \223206. 2 Rossiter JP, Repke JT, Morales AJ, et al. (1995). A prospective longitudinal eva luation of pregnancy in the Marfan syndrome. Am J Obstet Gynecol 173(5):1599 \200\2231606. CHAPTER 10 Heart disease in pregnancy 414 Valvular heart disease in pregnancy Valvular heart disease affects 1% of pregnancies and m ay be associated with an increased risk of adverse maternal, fetal, and neonatal outcomes. High-risk features include the following: \200 \200 Impaired LV function (EF <40%) Left-sided valve stenoses* (atrial stenosis [AS] with valve area <1.5 cm or mitral stenosis [MS] with valve area <2.0 cm2) Previous maternal cardiovasc ular event (CCF, TIA, CVA), or Symptoms* (NYHA class II or higher) Risk increases with each additive factor; see Box 10.1. 2 \200 Box 10.1 Classi \201 cation of valvular heart disease risk in pregnancy Low maternal and fetal risk \200 Asymptomatic AS with mean gradient <50 mmHg and normal LV function AR, NYHA Class I/II and normal LV function MR, NYHA Class I/II and normal LV function MV prolapse with no MR or wit h mild \200\223moderate MR and normal LV. Mild \200\223moderate MS (MV area >1.5 cm severe pulmonary hypertension Mild \200\223moderate PS \200 \200 \200 2, gradient <5 mmHg), no High maternal and fetal risk \200 \200 \200 \200 \200 Severe AS with or without symptoms AR and NYHA Class III or IV symptoms MS with NYHA Class II or higher MR with NYHA Class III or IV symptoms AV disease, MV disease, or both, resulti ng in severe pulmonary hypertension (PA pressure >75% systemic pressure) AV disease, MV dis ease, or both, with LV dysfunction (LVEF <40%) Maternal cyanosis Reduced functional status (NYHA Class III or IV) \200 \200 High maternal risk \200 \200 \200 Impaired LV systolic function (LVEF <40%) Previous heart failure Previous CVA or TIA High neonatal risk \200 \200 \200 \200 Maternal age <20 or >35 years Use of anticoagulant therapy throughout pregnancy Smoking dur ing pregnancy Multiple gestations Adapted from Reimold SC, Rutherford JD (2003). Valvular heart disease in pregnancy. N Engl J Med 349(1):52 \200\22359. MITRAL STENOSIS AND PREGNANCY 415 Mitral stenosis and pregnancy Mitral stenosis (MS) is important in pregnancy; although it i s asymptomatic at pregnancy onset, women may deteriorate secondary to tachycardia, arrhythm ias, or the increased cardiac output. The most common compli- cation is pulmonary edema sec ondary to increased left atrial pressure, and precipitated by increased heart rate or incre ased volume (such as occurs early in the third trimester or during the third stage of labor or following injudicious intravenous \202 uid therapy).1 The risk is increased with severe MS (mitral valve area <1 cm2), moder- ate or severe sympt oms prior to pregnancy, and in those diagnosed late in pregnancy.1 Management Women with severe mitral stenosis should be advised to delay pregnancy until aft er valvotomy or, if the valve is not amenable to valvotomy, until after mitral valve replac ement. B-Blockers decrease heart rate, increase diastolic \201 lling time,2 and decrease the risk of pulmonary edema. Diuretics should be continued in pregnancy. If medical therapy fails, or for those with sev ere mitral stenosis, balloon mitral valvotomy may be safely and successfully used in pregna ncy if the valve is suitable. Percutaneous balloon valvotomy carries a risk of major compli cations of about 1%, whereas for surgical valvotomy the \201 gures are closed valvot- omy , fetal mortality 5% \200\22315%, maternal 3%; open valvotomy, fetal mortality 15% \200\223 33%, maternal 5%. Women with mitral stenosis should avoid the supine and lithotomy positions as much as possi ble for labor and delivery. Fluid overload must be avoided, and even in the presence of oli guria, without signi \201 cant blood loss, the temptation to give intravenous colloid must be resisted. If pulmonary edema occurs it should be treated in the usual way with oxygen and diuretics. Introduction or reintroduction of a B-blocker may be useful to slow the heart rate. 1 Desai DK, Adanlawo M, Naidoo DP, et al. (2000). Mitral stenosis in pregnancy: a four-year experi- ence at King Edward VIII Hospital. Br J Obstet Gynaecol 107:953 \200\223958. 2 al Kasab SM, Sabag T, al Zaibag M, et al. (1990). Beta-adrenergic receptor blockade in the man age- ment of pregnant women with mitral stenosis. Am J Obstet Gynecol 163:37 \200\22340. CHAPTER 10 Heart disease in pregnancy 416 Other valve lesions Mitral regurgitation MR is usually due to mitral valve (MV) prolapse. I t is well tolerated as systemic vascular resistance is low in pregnancy. LV function is imp ortant in assessing risk (normal function carries a good prognosis). The most likely time for problems is immediately after delivery, because of autotransfusion , increased venous return, and increased peripheral vas- cular resistance. Aortic stenosis AS is usually congenital. If it is severe or symptomatic, advise the patien t to defer pregnancy until this is surgically corrected. If the patient is already pregnant and symptomatic early on, consider termination of the pr egnancy. Surgical replacement and balloon valvulo- plasty are both associated with signi \201 cant risks. Aortic regurgitation AR is usually well tolerated as reduced systemic vascular resistance i n pregnancy reduces the regurgitant volume. Vasodilators and diuretics are usually suf \201 cient treatment (stop ACE inhibitors and replace with nifed- ipine, hydralazine, etc.) . Risks are the same as those for MR. MECHANICAL HEART VALVES IN PREGNANCY 417 Mechanical heart valves in pregnancy The optimal management of women with prosthetic mechan ical heart valve replacements in pregnancy is controversial since the interests of the moth er and the fetus are in con \202 ict. These women require lifelong antico- agulation (see Box 10.2), and this must be continued in pregnancy because of the increased risk of thrombo sis. Warfarin is associated with warfarin embryopathy if given between 6 and 12 weeks gestation1 and with increased risks of miscarriage, stillbirth, and fetal intracerebral hemorrhage.2 There is some evidence that the adverse effects of warfarin are related to the dose require d to maintain the INR >2, with doses in excess of 5 mg being associated with higher risks o f teratogenesis, miscarriage, and stillbirth.3 Heparin and low-molecular-weight heparin, even in full anticoagulant doses, are associated with increased risks of valve thrombosis and embolic events1 \200\2234 but are not associat ed with fetal malformations and offer greater \202 exibility as delivery nears. Management There are three basic options: \200 Continue warfarin throughout pregnancy, stopping only for delivery. This is the safest opti on for the mother.1,2 Replace the warfarin with high-dose unfractionated or low-molecular- weight heparin from 6 to 12 weeks gestation to avoid warfarin embryopathy and then resume w arfarin and switch back to heparin as delivery nears. Use high-dose unfractionated or low-m olecular-weight heparin throughout pregnancy. The option is chosen will depend on several factors: \200 The type of mechanical valve. The risk of thrombosis is less with the newer bilea \202 et valves (e.g., CarboMedics) than with the \201 rst- generation ball and cage (e.g., Starr \200\223Edwards) or second-generation single tilting disc (e.g., Bjork \200\223Shiley) valv es. The position of the valve replacement. Valves in the aortic rather than the mitral posi tion are associated with a lower risk of thrombosis.4,5 The number of mechanical valves The dose of warfarin required to maintain a therapeutic INR Any previous history of embolic ev ents \200 \200 Whichever management option is chosen, warfarin should be discontin- ued and substituted wi th heparin for 10 days prior to delivery to allow 1 Chan WS, Anand S, Ginsberg JS (2000). Anticoagulation of pregnant women with mechanical h eart valves. Arch Intern Med 160:191 \200\223196. 2 Sadler L, McCowan L, White H, et al. (2 000). Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves. Br J Obstet Gynaecol 107:245 \200\223253. 3 Cotrufo M, De Feo M, De S anto L, et al. (2002). Risk of warfarin during pregnancy with mechan- ical valve prostheses . Obstet Gynecol 99:35 \200\22340. 4 Meschengieser SS, Fondevilla CG, Santarelli MT, et al. (1999). Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart 82 :23 \200\22326. 5 Elkayam U (1999). Pregnancy through a prosthetic heart valve. J Am Coll C ardiol 33:1642 \200\2231645. CHAPTER 10 Heart disease in pregnancy 418 clearance of warfarin from the fetal circulation. For delivery itself, heparin therapy is i nterrupted. Warfarin is recommenced postpartum. In the event of bleeding or the need for urgent deliver y in a fully anticoagulated patient, warfarin may be reversed with fresh frozen plasma (FFP ) and vitamin K, and heparin with protamine sulfate. Vitamin K should be avoided if possibl e since it renders the woman practically unable to anticoagulate with warfarin after delive ry. Women with prosthetic valve replacements all require antibiotic endo- carditis prophylaxis for delivery regardless of the mode of delivery.6,7 Urgent vaginal delivery should be avoided in a woman anticoagulated with Coumadin because of risk of fetal intracerebral hemorrhage. Box 10.2 Anticoagulation in pregnancy Unfractionated heparin \200 Often given in early and late pregnancy in patients with mechanical heart valves and valvul ar heart disease with AF. Used early in pregnancy, as it is not teratogenic. In peripartum period it is used for rapid control (and reversal) of anticoagulation in case emergency del ivery undertaken. Not as effective as other forms of anticoagulation Side effects: \200 ( monitor FBC), osteoporosis, alopecia hemorrhage (fetal and maternal), thrombocytopenia Low-molecular-weight heparin \200 Effective anticoagulant. Easier to monitor dosage schedule. Less likely to cause thrombocyt openia (but does still occur) \200 Side effects: maternal and fetal hemorrhage Warfarin \200 Effective oral anticoagulant. Studies show it to be more effective than unfractionated hepa rin at preventing valve thrombosis. \200 Side effects: avoid during this period if at all possible (use heparin). hemorrhage, teratogenic in \201 rst trimester, therefore Aspirin \200 Occasionally used in high-risk patients (AF, LV dysfunction, previous emboli) or those with previous prosthetic valve thrombosis \200 Side effects: hemorrhage, prolonged labor, low birth weight (in high doses), constriction o f ductus, fetal renal dysfunction, and hemostatis abnormalities 6 Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy (1982). Lancet 2:1323 \200\2231326. 7 Dajani AS, Taubert KA, Wilson W, et al. (1997). Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 277:1794 \200\2231801. ISCHEMIC HEART DISEASE 419 Ischemic heart disease The risk factors for myocardial infarction (MI) in pregnancy are the same as for the nonpregnant woman. The risk is increased in multigravid women and in those who smoke, and in women with diabetes, obesity, hyperten- sion, and hypercholesterolemia. Infarction most commonly occurs in the third trimester and affects the anterior wall of the heart.1 Maternal death rate is 20%. In pregnancy the underlying etiology is more likely to be due to nonatherosclerotic con- ditions (such as coronary artery thrombosis or dissectio n) than in the nonpregnant woman.2 Management \200 \200 Management of acute MI is as for the nonpregnant woman. Angiography should not be withheld if clinically indicated. The fetus should be shielded. Intravenous and intracoronary thromb olysis and percutaneous transluminal coronary angioplasty and stenting have all been succes sfully performed in pregnancy. B-blockers are safe in pregnancy. Both aspirin and There are less data for clopidogrel and glycoprotein IIb/IIIa inhibitors, although there are case re ports of their successful use. Statins should be discontinued for the duration of pregnancy as they are associated with an increased risk of malformations.2 ACE inhibitors and ARBs a re similarly contraindicated during pregnancy. \200 1 Roth A, Elkayam U (1996). Acute myocardial infarction associated with pregnancy. Ann Inte rn Med 125:751 \200\223757. 2 Edison RJ, Muenke M (2004). Central nervous system and limb a nomalies in case reports of \201 rst trimester statin exposure. N Engl J Med 350:1579 \200\2231582. CHAPTER 10 Heart disease in pregnancy 420 Hypertrophic obstructive cardiomyopathy (HOCM) The danger in pregnancy relates to left vent ricular out \202 ow tract obstruc- tion that may be precipitated by hypotension or hypovol emia. Provided these are avoided, pregnancy is usually well tolerated. Management B-Blockers should be continued in pregnancy or initiated for symptomatic women.1 Epidural anesthesia/analgesia carries the risk of vasodilation and hypo- tension with conse quent increased left ventricular out \202 ow tract obstruc- tion. Any hypovolemia will hav e the same effect and should be rapidly and adequately corrected.