Pedigree of a HCM family showing extensive phenotypic heterogeneity. Family member A = G+/HCM− at advanced age, noncardiac cause of death. Family member B = G+/HCM+ SD during exercise. Family member C = G+/HCM+ severe systolic dysfunction. Family member D = index patient of the family, first presentation with SD. Family member E and F = G+/HCM− (HCM hypertrophic cardiomyopathy, MYBPC3 myosin-binding protein C, G+ genotype positive, SD sudden death)
Parasternal long-axis echocardiography of hypertrophic cardiomyopathy patient. (a) Diastolic frame: asterix interventricular septum; square left ventricular posterior wall; arrow mitral valve. (b) Systolic frame: arrow systolic anterior movement of mitral valve
Both supraventricular and ventricular arrhythmias are prevalent in HCM patients. Atrial fibrillation is the most frequent, affecting more than 20 % of patients and associated with an unfavorable outcome . In all HCM patients, it is important to estimate the risk of SCD caused by ventricular arrhythmias and to select patients for prophylactic implantable cardioverter defibrillator (ICD) implantation. The implantation of an ICD for secondary prevention is universally accepted [1, 10]. The selection of patients for primary prevention of SCD with ICD implantation differs between Europe and America. The recent European Society of Cardiology guidelines promote the use of the HCM risk score, in which age, maximal wall thickness, LVOT gradient, left atrial dimension, the presence of ventricular tachycardia on Holter monitoring, unexplained syncope, and family history are used to calculate the SCD risk. A high risk is defined as the risk of SCD ≥6 % at 5 years, warranting ICD implantation [1, 8]. The American guidelines favor evaluation of major risk factors (family history, maximal wall thickness, unexplained syncope, the presence of ventricular tachycardia on Holter monitoring, and an abnormal blood pressure response to exercise) to estimate the SCD risk in order to select high-risk patients .
Echocardiography is the cornerstone of diagnosis in HCM. It is important to assess maximal LV wall thickness, LV systolic and diastolic function, left atrial dimension, and the presence of LVOT obstruction both at rest and during provocation. LVOT obstruction is present at rest in about a third of the patients; this increases to two thirds of the patients with exercise echocardiography . By convention, LVOT obstruction is defined as the presence of a LVOT gradient ≥30 mmHg. LVOT gradient ≥50 mmHg is considered as threshold at which LVOT obstruction becomes hemodynamically important and is generally accepted as the threshold for invasive therapies in symptomatic HCM patients on optimal medical therapy [1, 12]. Provocation of LVOT obstruction with the Valsalva maneuver in different positions (sitting, semi-supine, and in some cases standing) is recommended in all patients (Fig. 11.3). Exercise echocardiography is recommended in symptomatic HCM patients with LVOT gradients <50 mmHg after bedside manoeuvre. The presence and magnitude of LVOT obstruction are important for the management of symptoms and the assessment of the SCD risk .
Provocation of left ventricular outflow tract obstruction (LVOT) with Valsalva. (a) LVOT gradient 7 mmHg at rest. (b) LVOT gradient 80 mmHg during Valsalva
11.2 Pregnancy Outcomes
The most common causes of complications are caused by diastolic dysfunction of the hypertrophied noncompliant LV, LVOT obstruction, and arrhythmias . The maternal mortality rate is very low and limited to those patients with HCM who were significantly symptomatic before pregnancy, had significant impaired LV function before pregnancy, and/or had high LVOT gradient . Most women who experience symptoms during pregnancy are already known with similar symptoms before pregnancy . In pregnant HCM patients, the New York Heart Association (NYHA) class > II and the presence of LVOT obstruction are related with maternal and neonatal events [14, 16, 17]. Patients known with structural heart disease and arrhythmias are more likely to experience complaints during pregnancy .
11.3.1 Antenatal Considerations
Current cardiac medication and its use during pregnancy should be discussed with the patient, as some medications might need to be adjusted to prevent adverse fetal events. The US Food and Drug Administration (FDA) classifies drugs used during pregnancy and breastfeeding from category A (=safest) to X (=known danger) . The medications that are most widely used in HCM patient include beta-blockers, calcium antagonists, disopyramide, amiodarone, diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and vitamin K antagonists (VKA). In HCM patients whose symptoms are controlled by beta-blockers, the medication should be continued during pregnancy (class IIa, level C recommendation) . The fetal events are usually not severe and manageable, including growth retardation, neonatal bradycardia, and hypoglycemia. Monitoring of fetal growth and of neonatal condition is recommended in all pregnant patients on beta-blockers. The use of metoprolol (FDA class C) is preferred over atenolol (FDA class D), because the latter has been associated with more growth retardation. The calcium antagonists verapamil and diltiazem (both FDA class C) can be used during pregnancy when their benefits outweigh the potential risk as it can cause AV block in the fetus. Disopyramide (FDA class C) should be used with caution since it can cause uterine contractions. Amiodarone (FDA class D) is used in HCM for rhythm control in atrial fibrillation and for the treatment of ventricular arrhythmias. Amiodarone can cause growth retardation, fetal thyroid toxicity, bradycardia, and premature birth and should only be used when absolutely necessary. ACE inhibitors and ARBs are contraindicated in women who are pregnant or wish to become pregnant, because of the teratogenic effects on the fetal kidney. Loop diuretics can be used during pregnancy, but aldosterone antagonist should be avoided. All HCM patients with atrial fibrillation have an indication for oral anticoagulants; the use of the CHA2DS2-VASc score is not recommended to calculate the stroke risk (class I, level C recommendation) . In the first trimester, low molecular weight heparin is recommended, because of the risk of embryopathy of VKA. In the second and third trimester, VKA (FDA class D) is recommended. After the 36th week of gestation, low molecular weight heparin is recommended because of the bleeding risk during delivery. The new oral anticoagulants are contraindicated because of proven toxicity in animals and lack of data in humans.
11.3.2 Follow-Up During Pregnancy
Development of heart failure symptoms is relatively uncommon during pregnancy, occurring in <5 % of previously asymptomatic HCM patients and in 15 % of the overall cohort. Clinical deterioration is twice as common in patients with LVOT obstruction compared to those without . Beta-blockers (metoprolol) should be started in women who develop symptoms during pregnancy (class I, level C recommendation). Loop diuretics may be necessary to limit fluid retention . The 2011 ESC guidelines on the management of cardiovascular disease during pregnancy also advise to consider beta-blockers in all HCM patients with more than mild LVOT obstruction or a maximal wall thickness exceeding 15 mm, but this is not recommended in the more recent ESC HCM guideline [1, 13]. The latter recommends starting beta-blockers in women who develop symptoms during pregnancy . Women with arrhythmias before pregnancy are more likely to experience arrhythmias during pregnancy, but pregnancy alone does not seem to significantly increase the risk of arrhythmia [16, 17]. Cardioversion for poorly tolerated atrial fibrillation should be considered during pregnancy; this should be performed in centers with the ability for cardiac monitoring and emergency caesarean section (class IIa, level C recommendation) .
G+/HCM− women are in WHO class I and don’t need specific cardiac follow-up during their pregnancy after HCM is excluded by ECG and echocardiography before or shortly after conception.
Pregnant HCM patients who are in WHO class II are at low to moderate risk and should be assessed each trimester. Those in WHO class III have a high risk of complications and should be followed twice a month in specialized centers, by a multidisciplinary team. This team should consist of cardiologists, obstetricians, and anesthesiologists in experienced maternal-fetal medicine units. HCM patients that are in WHO class IV should be advised against pregnancy, but if they are pregnant and don’t consider termination follow-up should be arranged according to those women who are in class III .
During follow-up, special attention should be paid to symptoms and signs of heart failure and arrhythmias, LV function, and LVOT obstruction. Echocardiography should be performed each trimester and when new symptoms occur.
11.3.3 Management During Labor and Delivery
By the end of the second trimester, the multidisciplinary team should make a delivery plan. During labor cardiac output is increased by catecholamine-induced increase in heart rate and stroke volume. Tachycardia will shorten the LV diastolic filling period, decreasing preload and increasing LVOT obstruction. Venous return is impaired by the performance of the Valsalva manoeuvre with maternal pushing during labor and delivery and this might also increase LVOT obstruction. During labor the patient should be positioned in a lateral decubitus position in order to attenuate the hemodynamic impact of uterine contractions.
Substantial blood loss during delivery can lead to reduction of venous return and a relative increase in LVOT obstruction. In a recent paper describing the association of cardiomyopathy with adverse cardiac events during delivery, one fifth of the HCM patients experienced either heart failure or arrhythmias at delivery .