ABC | Volume 114, Nº5, May 2020

Statement Brazilian Cardiology Society Statement for Management of Pregnancy and Family Planning in Women with Heart Disease – 2020 Arq Bras Cardiol. 2020; 114(5):849-942 Methyldopa ( β 2-adrenergic receptor agonist): Non- teratogenic, considered safe and effective in the treatment of gestational hypertensive disease with favorable outcomes in primary and secondary outcomes such as blood pressure control, fetal growth, and prematurity. Warning maternal effects such as postural hypotension, lupus-like syndrome, depression, nasal congestion, drowsiness, and liver toxicity have been reported in 1% of treated cases. 67,68 Hydralazine: direct arteriolar vasodilator for oral or intravenous use in hypertensive emergencies. Adverse effects are maternal symptoms of "like" lupus and fetal thrombocytopenia. 69 Clonidine: alpha-2 agonist has divergent hemodynamic effect in reducing vascular resistance versus reduction in cardiac output, and the consequent impact on fetal growth. Abrupt suspension may cause rebound hypertension. It is not teratogenic. It is available transdermal. 70 Diuretics are indicated in hypervolemia and HF; however, the reduction in plasma volume, cardiac output, and placental flow is the major restriction on diuretic use during pregnancy. Its use during pregnancy has not been related to detrimental effects to the fetus. Furosemide is the most commonly used, while hydrochlorothiazide has been related to lower birth weight, jaundice, and neonatal thrombocytopenia. 71 Beta-blocker: atenolol is not recommended because its use is associated with IUGR and low birth weight newborns. 71 Amlodipine: may be considered second-line treatment without reference to being teratogenic when used in the first trimester of pregnancy. 71 ACEI, ARB, direct renin inhibitors and aldosterone antagonists are contraindicated in pregnancy and should not be prescribed in women who wish to become pregnant. These medications cause renal dysgenesis, oligohydramnios, renal failure, IUGR, neonatal anuria, and fetal death, particularly in the second and third trimesters of pregnancy. 72 However, ACE inhibitors may be used in lactation. Aldosterone antagonists have antiandrogenic effects on the male fetus and are contraindicated in lactation. 52,73 2.5.2. Antiarrhythmic Drugs (Table 10) Adenosine: nucleoside with a half-life of seconds. It is safe, but adverse effects include bradyarrhythmias, dyspnea, chest pain and flushing. 74,75 Beta-blockers : These are the most commonly used drugs during pregnancy. They are not teratogenic. Controlled studies show a higher frequency of neonatal bradycardia and hypoglycemia, as well as a higher risk of prematurity and small newborns for gestational age. 76-78 Atenolol: hydrophilic with renal elimination, is contraindicated by the high risk of IUGR. 79,80 Propranolol is safe; however, depending on the dose, IUGR, hypoglycemia, polycythemia, and hyperbilirubinemia may occur. 81 Metoprolol is well tolerated, with high clearance in the second half of pregnancy. Succinate is safer than tartrate because doses are lower and maybe fractionated. 82,83 Sotalol is associated with point torsades due to QT interval prolongation. Sotalol is higher in breast milk and should be suspended during lactation. In cases of lactation maintenance, electrocardiographic control should be performed in the mother and the newborn. According to ESC Guidelines, 2018, 52 sotalol was contraindicated in pregnancy and lactation because of the risk of sudden maternal-fetal death. The proposal is a replacement for propafenone or flecainide. However, the restriction on the use of sotalol during pregnancy and lactation is still controversial, as the results in controlling complex arrhythmias have been satisfactory in the practice of the specialists. Although there are no adequate studies, sotalol appears to be safer compared to amiodarone. 84-85 Amiodarone : lipophilic, accumulates in skeletal muscle and adipose tissue, with half-life from weeks to months. Warning effects are thyroid dysfunction (causing neonatal hypothyroidism in 17 to 25% of cases) and impaired neurological development. Should be contraindicated in pregnancy. 86-87 Lidocaine : more studied as an anesthetic agent than antiarrhythmic. Sixty percent of it is bound to plasma protein and rapidly entering the maternal circulation and placenta. It may lead to depression of the fetal central nervous system when used at high doses. 73,88 Propafenone : recommended for the prevention of supraventricular tachycardia in patients with Wolff Parkinson White syndrome, atrial tachycardia and atrial fibrillation refractory to nodal blocking agents. 52 Procainamide : associated with maternal lupus syndrome. 89 2.5.3. Drugs in Heart Failure (Table 11) Carvedilol: There is a lack of studies. It is the first choice of cardioselective beta-blocker. It is not teratogenic and has not been associated with IUGR. 90 Bisoprolol : Not associated with an increased risk of miscarriage or fetal malformation when used in the first trimester of pregnancy. However, IUGR cannot be ruled out during prolonged use throughout pregnancy. 52,78 Hydralazine: A drug that replaces ACEI and ARB. 52 Nitrates: Not routinely used and not teratogenic. Low maternal tolerance due to hypotension and headache. 52 Sacubitril / valsartan: is contraindicated during pregnancy and although there are no studies on human milk excretion, there is no recommendation for use during breast-feeding. Ivabradine : Animal studies show its association with malformation, bradycardia and altered fetal growth. 2.5.4. Antiplatelet (Table 12) Aspirin: It is safe at low doses at any stage of pregnancy. 52,91,92 Not teratogenic, risk of maternal and fetal bleeding. Should be discontinued five days before delivery. 52,93,94 Clopidogrel: There are no studies to ensure its use during pregnancy. It does not appear to be teratogenic. The use of clopidogrel should be recommended in very specific cases, as discontinuation of clopidogrel may impair the treatment of the disease for which it is indicated. 93,94 866