INTRODUCTION — Pregnancy is associated with substantial hemodynamic changes, including 30 to 50 percent increases in both cardiac output and blood volume. In patients who are pregnant with a history of heart failure (HF) or other cardiovascular disorders, these demands can lead to clinical decompensation. In addition, patients without a history of cardiovascular disease can develop HF due to diseases acquired during pregnancy, such as peripartum cardiomyopathy. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis".)
In patients with HF who plan to become pregnant, are pregnant, or are breastfeeding, the medications used to treat HF must be adjusted to avoid toxicity to the fetus or infant. The evaluation and management of HF during pregnancy and breastfeeding will be reviewed here.
The general approach to pregnancy in patients with known congenital or acquired heart disease, treatment of peripartum cardiomyopathy, treatment of hypertrophic cardiomyopathy during pregnancy, and overviews of the management of acute and chronic HF are presented separately:
●(See "Acquired heart disease and pregnancy".)
●(See "Pregnancy in women with congenital heart disease: General principles".)
●(See "Peripartum cardiomyopathy: Treatment and prognosis".)
●(See "Treatment of acute decompensated heart failure: General considerations".)
CATEGORIES OF HEART FAILURE — HF is categorized according to acuity of presentation (chronic versus acute) as well as according to whether the left ventricular ejection fraction (LVEF) is reduced (≤40 percent) or preserved. HF is also classified as being predominantly right and/or left sided.
Chronic versus acute conditions — In patients who are pregnant or considering pregnancy, issues related to HF management arise in the following settings:
●Preexisting HF – Patients with a history of chronic HF or other cardiovascular disorders can present in a stable condition either prior to or in the early stages of pregnancy. In such patients, management focuses on the adjustment of chronic medical therapies and monitoring for decompensation.
Conditions that increase the risk of developing HF during pregnancy include cardiomyopathy (eg, dilated cardiomyopathy or hypertrophic cardiomyopathy), mitral stenosis, aortic stenosis, and severe mitral or aortic regurgitation [1,2]. In addition, adult patients with congenital heart disease are at risk of developing HF during pregnancy [1-3]. In adult survivors of pediatric cancer exposed to cardiotoxic chemotherapy or chest irradiation in the past but who are without chemotherapy-related cardiac dysfunction, the incidence of HF or LV dysfunction during pregnancy is rare. However, amongst those that have had a history of chemotherapy-related cardiac dysfunction, the odds of developing HF during and within one year following pregnancy are 47.4-fold higher, according to a meta-analysis [4].
Ischemic heart disease is uncommon in this population. (See "Acquired heart disease and pregnancy" and "Pregnancy in women with congenital heart disease: General principles".)
●Newly recognized or incident HF – Patients can present with decompensated HF during pregnancy or in the peripartum period. Such decompensation can occur in patients with preexisting disease [5], or it can be the result of disease acquired during pregnancy. Because pregnancy can be proarrhythmic, patients with preexisting lesions such as mitral stenosis can develop arrhythmias during pregnancy that precipitate HF. Examples of cardiovascular disorders that can develop during pregnancy include peripartum cardiomyopathy, infective endocarditis, sepsis, and pericardial disease. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis".)
EVALUATION — The nature of the initial evaluation in pregnant patients with (or at risk for) HF varies according to the setting. Risk assessment for maternal cardiovascular complications during pregnancy should utilize the modified World Health Organization classifications [6]. Stable as well as decompensated patients require joint cardiac and obstetric care, including baseline and follow-up maternal transthoracic echocardiograms as well as fetal ultrasound examinations [7].
Stable patient — Patients with a history of HF or other cardiovascular disorders often present in a stable, well-compensated condition prior to or in the early stages of pregnancy. The initial approach to such patients involves assessing the cardiovascular risks associated with pregnancy and discussing these risks with the patient. There are increased risks for both the mother and for the fetus/neonate (low birth weight/prematurity). (See "Acquired heart disease and pregnancy", section on 'Assessing risk' and "Pregnancy in women with congenital heart disease: General principles", section on 'Preconception and prenatal care'.)
A baseline maternal cardiovascular evaluation should include the following:
●A careful history (including review of medication list) and physical examination with consideration of physiologic changes during pregnancy. Findings such as mild pedal edema and presence of a fourth heart sound (S4) may be observed during uncomplicated pregnancy.
●Assessment of New York Heart Association functional class (table 1).
●An electrocardiogram (ECG).
●Echocardiography if not recently performed or if there have been any changes in symptoms or signs of HF.
●Laboratory tests, including electrolytes and renal function tests if there have been clinical changes or recent adjustments in diuretic regimen. Plasma B-type natriuretic peptide (BNP) level may be helpful in identifying high-risk patients, though data on its specificity in this setting are limited [8]. Median BNP levels during normal pregnancy are approximately twofold those in nonpregnant controls [9], while median BNP levels in a series of pregnant patients with heart disease were over twofold those in pregnant patients without heart disease [8].
●In select cases, cardiovascular magnetic resonance or other cardiac imaging studies may be required (eg, congenital heart disease with right ventricular [RV] dilation/dysfunction).
New or acute heart failure — Patients with new or acute decompensated HF most commonly present with progressive dyspnea or perhaps a persistent cough, which may or may not be associated with chest discomfort. The diagnosis is made using a constellation of clinical signs and symptoms and selected laboratory findings. The general approach to the diagnosis of new or acute decompensated HF is presented in detail separately. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Approach to diagnosis and evaluation of acute decompensated heart failure in adults".)
The initial maternal cardiovascular evaluation usually includes the following:
●A focused history and physical examination with particular attention to evidence of preexisting cardiovascular disease.
●Echocardiography, which may reveal previously undetected structural heart disease (eg, valve abnormalities or congenital heart disease) or worsening LV function.
●An ECG, which may reveal LV or RV hypertrophy, left atrial abnormalities, myocardial ischemia, or atrial fibrillation.
●Laboratory tests, including a complete blood count, electrolytes, and renal function tests. A BNP level may be helpful for risk stratification [8] or if the diagnosis of HF is uncertain (noting that median BNP levels during normal pregnancy are approximately double those in nonpregnant controls). In selected patients, additional tests (eg, arterial blood gas, cardiac troponin levels) may be appropriate. (See "Approach to diagnosis and evaluation of acute decompensated heart failure in adults", section on 'Diagnostic evaluation'.)
●A chest radiograph is not necessary to establish the diagnosis of HF if there is clear clinical evidence of pulmonary edema. If, despite a thorough physical exam, the diagnosis of pulmonary edema is still uncertain, and a chest radiograph is necessary to make that diagnosis, it should be performed with fetal shielding to minimize fetal radiation exposure. (See "Diagnostic imaging in pregnant and nursing patients" and "Approach to diagnosis and evaluation of acute decompensated heart failure in adults", section on 'Chest radiograph'.)
Differential diagnosis — The differential diagnosis for HF symptoms during pregnancy or in the peripartum period includes the following conditions:
●Uncomplicated pregnancy is commonly accompanied by breathlessness, easy fatigability, decreased exercise tolerance, basal rales (that clear with cough or deep breathing) and peripheral edema. Physical examination (elevated jugular venous pressure and persistent rales) and lab findings (eg, evidence of elevated intracardiac pressures and systolic and/or diastolic dysfunction on echocardiography, BNP elevated above levels seen in pregnancy) distinguish benign symptoms and signs of normal pregnancy from HF. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)
●Pulmonary edema due to tocolytic therapy or preeclampsia/eclampsia. These conditions are suggested by the clinical setting of administration of tocolytic therapy (and generally large amounts of intravenous fluids) or evidence of preeclampsia/eclampsia (hypertension plus proteinuria or other characteristic findings). (See "Acute respiratory failure during pregnancy and the peripartum period", section on 'Pulmonary edema'.)
●Amniotic fluid embolism is suggested by abrupt onset of hypotension, hypoxemia, disseminated intravascular coagulation, and coma or seizures. (See "Amniotic fluid embolism".)
●Pulmonary embolism that may be distinguished from HF by physical examination and chest radiograph (if obtained). Of note, acute large pulmonary embolus can cause elevations in BNP or N-terminal pro-BNP (similar to levels seen with HF) and a dilated hypokinetic RV on echocardiogram. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Acute respiratory failure during pregnancy and the peripartum period", section on 'Pulmonary embolism'.)
●Pneumonia is suggested by clinical history and physical examination as well as by chest radiograph (if obtained). (See "Acute respiratory failure during pregnancy and the peripartum period", section on 'Pneumonia' and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)
●Myocardial infarction is diagnosed based upon ischemic symptoms, characteristic ECG abnormalities, and elevations in cardiac biomarkers. (See "Acute myocardial infarction and pregnancy" and "Diagnosis of acute myocardial infarction".)
COUNSELING — Management of a woman with HF (or at risk for HF) contemplating pregnancy includes counseling the patient regarding the expected prognosis and potential risks of pregnancy. The discussion should be based upon an individualized assessment of risk. Counseling should ideally occur prior to pregnancy.
Specifically, patients with a preexisting dilated cardiomyopathy should be informed about the risk of deterioration during pregnancy and peripartum, which is dependent upon the severity of systolic dysfunction [10]. Since the risk of maternal mortality is very high during pregnancy for patients with dilated cardiomyopathy with LVEF <30 percent, avoidance of pregnancy is advised. For those patients at very high risk who become pregnant, termination of pregnancy should be discussed with the patient [10-12].
Cardiac transplant recipients are generally advised to avoid pregnancy during the first year after transplantation when the risk of rejection is greatest and immunosuppressive therapy most aggressive. (See "Heart transplantation in adults: Pregnancy after transplantation".)
Discussion of prognosis with patients with peripartum cardiomyopathy is discussed separately. (See "Peripartum cardiomyopathy: Treatment and prognosis", section on 'Prognosis'.)
MANAGEMENT GOALS — Management goals for pregnant patients with HF and for patients with HF contemplating pregnancy are similar to those in nonpregnant patients. These include the following:
●Relief of symptoms.
●Optimizing hemodynamic status. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults".)
●When possible, continuation (or initiation) of chronic therapies that improve long-term outcomes (including mortality) in patients with chronic cardiovascular disorders (eg, beta blocker therapy to treat HF with reduced ejection fraction and antihypertensive therapy in patients with hypertension).
●Treatment of precipitating factors (eg, anemia, arrhythmias, infection, thyroid disorders).
General discussions of the treatment of acute and chronic HF are presented separately [13]. (See "Treatment of acute decompensated heart failure: General considerations".)
TREATMENT REGIMENS
Chronic heart failure — Components of therapy for chronic HF include lifestyle modification, review of drugs, vaccinations (pneumococcal and annual influenza), pharmacologic therapy, and device therapy (including cardiac resynchronization therapy and/or implantable cardioverter-defibrillator therapy).
●HFrEF – Drugs used to treat chronic HF with reduced ejection fraction (HFrEF) during pregnancy include diuretics, beta blockers, hydralazine plus nitrate, and digoxin. (See 'Drugs' below.)
•During pregnancy, clinical HF including pulmonary congestion is treated with a diuretic. (See 'Diuretics' below and "Use of diuretics in patients with heart failure".)
•Beta blockers are generally continued during pregnancy in patients with chronic HFrEF who are taking a beta blocker as part of a chronic regimen to improve long-term outcomes. (See 'Beta blockers' below.)
•For pregnant patients with symptoms of HF, hydralazine plus isosorbide dinitrate is a reasonable alternative to vasodilators contraindicated in pregnancy. (See 'Vasodilators' below.)
•For pregnant patients with symptoms of HF due to systolic dysfunction that persist despite diuresis and vasodilator therapy, digoxin can be used to treat symptoms. (See 'Digoxin' below.)
We avoid the following agents due known toxicities and effects or the absence of safety data:
•Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and sacubitril-valsartan are contraindicated. (See 'Avoid angiotensin inhibition' below.)
•We avoid mineralocorticoid receptor antagonists. (See 'Aldosterone antagonists' below.)
•We avoid sodium-glucose co-transporter 2 (SGLT2) inhibitors during pregnancy given the absence of human safety data supporting use during pregnancy. (See 'Sodium-glucose co-transporter 2 inhibitors' below.)
If indicated, implantation procedures for cardiac resynchronization therapy and/or implantable cardioverter-defibrillator therapy are performed prior to or following pregnancy, if possible, to avoid the risk of radiation to the fetus. (See "Diagnostic imaging in pregnant and nursing patients".)
●HFpEF – For the treatment of HF with preserved ejection fraction (HFpEF), we avoid the use of mineralocorticoid receptor antagonists, sacubitril-valsartan, and SGLT2 inhibitors. (See 'Aldosterone antagonists' below and 'Sodium-glucose co-transporter 2 inhibitors' below and 'Avoid angiotensin inhibition' below.)
Acute heart failure — Components of therapy for acute HF include supplemental oxygen therapy and pharmacologic therapy (including diuretic therapy in patients with clinical HF including those with pulmonary edema). (See "Treatment of acute decompensated heart failure: Specific therapies".)
For pregnant patients with severe decompensated HF and stable or elevated blood pressure, we suggest the addition of intravenous vasodilator therapy with nitroglycerin to the medical regimen. In selected cases, the cautious use of nitroprusside may be an appropriate alternative to nitroglycerin. Hemodynamic and fetal monitoring should be employed, as appropriate. (See 'Vasodilators' below and "Treatment of acute decompensated heart failure: Specific therapies", section on 'Vasodilator therapy'.)
Beta blocker therapy in pregnant patients with acute decompensated HFrEF is managed in the same manner as in nonpregnant patients with decompensated HFrEF. Beta blockers are not initiated in the setting of acute decompensated HFrEF. Similarly, patients on chronic beta blocker therapy who develop acute decompensated HFrEF often have the dose reduced or therapy withheld during initial treatment. (See 'Beta blockers' below and "Treatment of acute decompensated heart failure: General considerations".)
Pregnant patients with severe decompensated HFrEF and hypotension may benefit from intravenous inotropic therapy. (See 'Inotropes' below and "Inotropic agents in heart failure with reduced ejection fraction".)
Refractory heart failure — For patients with acute or chronic HF that is refractory to treatment, specialized strategies include intravenous inotropic therapy and temporary mechanical circulatory support. (See "Management of refractory heart failure with reduced ejection fraction".)
Limited experience with pregnancy and delivery in patients with LV assist devices has been described [14]. Concerns include maternal and fetal risks such as thromboembolism and the need for anticoagulation and the risk of bleeding exacerbated by the occurrence of acquired von Willebrand syndrome.
Experience with pregnancy after cardiac transplantation has grown. Cardiac transplant recipients are generally advised to avoid pregnancy during the first year posttransplantation when the risk of rejection is greatest and immunosuppressive therapy most aggressive. (See "Heart transplantation in adults: Pregnancy after transplantation".)
DRUGS — Due to the unique issues related to pregnancy and lactation, each medication to treat HF must be carefully considered in these clinical settings [15]. Since there are changes in the volume of distribution and glomerular filtration rate during pregnancy, dosing of certain medications may need to be increased during pregnancy.
The following discussion addresses the role of medications commonly used for the treatment of HF during pregnancy and lactation.
Avoid angiotensin inhibition — Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and sacubitril-valsartan, which are part of the standard long-term therapeutic regimen in nonpregnant patients with HF with reduced ejection fraction (HFrEF), are contraindicated during pregnancy. These drugs are associated with a high risk of adverse effects in the fetus, with risks during all trimesters of pregnancy, particularly the second and third trimesters. Consequences include fetal renal failure and even neonatal death [16-18]. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)
In treating a woman with HF who already taking an ACE inhibitor, ARB, or angiotensin receptor-neprilysin inhibitor (ARNI), two key questions should be addressed:
●When should chronic ACE inhibitor, ARB, and ARNI therapy be discontinued (ie, when planning to conceive or only after pregnancy is confirmed)?
•Due to the risks of embryopathy associated with ACE inhibitor, ARB, or ARNI use during pregnancy, we recommend discontinuation of these medications when a woman with chronic stable HF is attempting conception. Clinical follow-up and echocardiography are suggested following the discontinuation of any of these agents in a patient to determine whether clinical status, LV dilation, or LVEF has worsened. If the LVEF drops after discontinuation of ACE inhibitor therapy, the risk of pregnancy should be reconsidered.
•If an ACE inhibitor, ARB, or ARNI is inadvertently taken during the first trimester, immediate discontinuation of the medication with subsequent monitoring including fetal ultrasound is recommended [10].
●When should ACE inhibitor, ARB, or ARNI therapy be replaced with hydralazine plus nitrate therapy? (See 'Hydralazine plus nitrate' below.)
Levels in breast milk of ACE inhibitors are low and not expected to cause adverse effects in breastfed infants [19]. An ACE inhibitor that has been studied in breast milk and/or breastfed infants (such as enalapril, captopril, quinapril, or benazepril) is preferred. There are no data on ARB or ARNI safety during breastfeeding, and therefore we do not recommend using an ARB or ARNI during breastfeeding. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Drug options during breastfeeding'.)
Beta blockers — Beta-adrenergic blocking agents, such as extended-release metoprolol, carvedilol, and bisoprolol, are important components of the treatment regimen for patients with chronic HF due to systolic dysfunction.
During pregnancy — Much of what is known about the use of beta blockers in pregnancy is from data on its use to treat hypertension in pregnant patients. These agents are generally safe and effective during pregnancy, although there may be an increased rate of fetal growth restriction when they are administered [20,21]. In general, agents that are beta-1 selective (eg, metoprolol) are preferable, since these agents are less likely to interfere with beta-2 mediated uterine relaxation and peripheral vasodilation. However, atenolol should not be used during pregnancy since its use is associated with fetal growth restriction [10,22].
Continuation of chronic beta blocker therapy in stable asymptomatic patients with HFrEF who are pregnant is suggested, assuming that there is no discernible adverse effect on the fetus. Fetal growth should be monitored by ultrasound. Beta blockers are not associated with an increased risk of congenital anomalies, although occasional cases of neonatal apnea, hypotension, bradycardia, and hypoglycemia have been reported, especially after prolonged use of propranolol. Infants born to mothers treated with beta blockers should be observed for 72 to 96 hours after parturition.
Beta blockers are not initiated in the setting of acute decompensated HFrEF. Similarly, patients on chronic beta blocker therapy who develop acute decompensated HFrEF often have the dose reduced or therapy withheld during initial treatment. Once the patient with an episode of acute decompensation has stabilized, chronic beta blocker therapy may be initiated, usually after several days. (See "Treatment of acute decompensated heart failure: General considerations".)
During nursing — The excretion of beta blockers into breast milk appears to be higher for drugs with low protein binding. Risk of accumulation of beta blocker in infants rises with degree of renal excretion. Despite these variations, the amount of beta blocker that would be ingested by a nursing infant is generally small and measured serum beta blocker levels in breastfed infants have generally been very low or undetectable, with limited exceptions (eg, atenolol) [19,23].
Among the three beta blockers recommended to treat stable HFrEF, we suggest use of extended-release metoprolol in nursing mothers, based upon the following considerations:
●Though metoprolol (which is 10 percent protein bound and 40 percent renally excreted) is excreted into breast milk, breastfed infants have had very low or undetectable serum levels [19,23]. Limited studies on the use of metoprolol during breastfeeding have reported no adverse reactions in breastfed infants.
●Since carvedilol is highly protein bound (95 percent) and has low renal excretion (1 percent), carvedilol likely presents a low risk for accumulation in breastfed infants [19]. However, since published experience with carvedilol during breastfeeding is lacking, other agents are preferred when nursing a newborn or preterm infant.
●Since bisoprolol has relatively low protein binding (30 percent) and moderately high renal excretion (50 percent), it presents a moderately high risk for accumulation in breastfed infants [19]. Since there is little published experience with bisoprolol during breastfeeding, other agents are preferred when nursing a newborn or preterm infant.
Although some studies suggest that atenolol may also be beneficial in HFrEF, we avoid atenolol use in nursing mothers. Atenolol is 10 percent protein bound and thus relatively extensively excreted into breast milk [19,23]. It is also extensively renal excreted (85 percent), which presents a high risk for accumulation in infants. Therefore, other agents are preferred while nursing a newborn or preterm infant.
When a nursing mother is taking a beta blocker, the infant should be observed for evidence of beta blockade (bradycardia) and it is prudent to consult the managing pediatrician.
Aldosterone antagonists — The aldosterone antagonists spironolactone and eplerenone, which compete with aldosterone for the mineralocorticoid receptor, prolong survival in selected patients with HF. However, in animal studies, the antiandrogen effects of spironolactone caused feminization of the male fetus. There are neither data nor clinical experience to support the safety of these agents during pregnancy. Thus, we suggest that these agents not be used during pregnancy.
Limited data suggest that spironolactone use is acceptable during breastfeeding since the maternal diuretic effect is unlikely to be potent enough to affect lactation, and the dose to the breastfeeding infant is low [19]. In patients with HF who are breastfeeding, we do not use eplerenone; data are lacking on the use of eplerenone during breastfeeding.
Sodium-glucose co-transporter 2 inhibitors
During pregnancy — Sodium-glucose co-transporter 2 (SGLT2) inhibitors should be avoided during pregnancy. There are inadequate safety data in pregnant patients to determine the drug-associated risk for major birth defects or miscarriage. Based on animal studies, adverse effects on renal development may be seen in a timeline that correlates with the second and third trimesters of human pregnancy.
During nursing — We do not administer SGLT2 inhibitors to patients who are breast feeding. It is not known whether either of these agents is present in breast milk, and, therefore, both drugs should be avoided in lactating patients due to the potential for serious adverse effects on the nursing infant.
Digoxin — Digoxin is generally safe in pregnancy, despite anecdotal reports of adverse effects [24,25]. Dosing may need to be increased to achieve a therapeutic effect during pregnancy. The decision to do so should be based upon the perceived adequacy of the therapeutic effect rather than purely on serum levels [26]. Transplacental passage of digoxin has been documented and this pharmacokinetic property has been used for the in-utero treatment of fetal tachyarrhythmias [27].
During pregnancy, digoxin can be particularly useful for two reasons:
●The use of conventional HF therapies is limited.
●The increased physiologic demands of pregnancy can exacerbate HF symptoms.
Similar to nonpregnant patients, the indications for digoxin in pregnant patients include:
●The persistence of symptoms (such as fatigue, dyspnea, and exercise intolerance) despite optimal treatment with agents safe for use during with pregnancy.
●For control of the ventricular rate in HF patients with atrial fibrillation who cannot achieve adequate control on beta blockers alone.
During nursing — Digoxin levels in breast milk are low; the dose to a breastfed infant is small and no adverse effects have been reported in newborns [19]. If an intravenous dose of digoxin is administered to a nursing mother, avoidance of breastfeeding for two hours will lessen the dose ingested by the infant.
Ivabradine — Given lack of evidence of safety during pregnancy and nursing, we suggest avoiding ivabradine use in pregnant or nursing patients.
Vericiguat — We do not use vericiguat in patients who are pregnant, who seek to become pregnant, or who are breastfeeding.
Diuretics — Diuretics are given for HF during pregnancy for symptomatic relief of pulmonary edema (eg, paroxysmal nocturnal dyspnea or exertional dyspnea) and also for marked peripheral edema. For treatment of HF, loop diuretics are generally preferred over thiazide diuretics and potassium-sparing diuretics. (See "Use of diuretics in patients with heart failure".)
Treatment with loop diuretics (without waiting for response to sodium restriction) is recommended for patients with any degree of pulmonary congestion. Potential maternal complications of loop diuretic use are similar to those of nonpregnant patients and include volume contraction, metabolic alkalosis, decreased carbohydrate tolerance, hypokalemia, hyponatremia, hyperuricemia, and pancreatitis. Potential risks to the fetus are related to the potential for intravascular volume contraction and reduced placental perfusion.
A thiazide diuretic may be added if volume cannot be adequately controlled with a loop diuretic alone. However, there are reports of bleeding disorders and hyponatremia among neonates of patients who have taken thiazide diuretics during pregnancy [28].
Volume contraction caused by diuretics might decrease lactation [19]. No information is available on the use of loop diuretics during breastfeeding. Moderate doses of thiazide diuretics (eg, up to 50 mg daily of hydrochlorothiazide) are acceptable during lactation.
Vasodilators — Vasodilator therapy improves cardiac output in moderate to severe HF and slows the rate of myocardial deterioration at all stages by inducing afterload reduction.
Hydralazine plus nitrate — Because ACE inhibitors, ARBs, and sacubitril-valsartan are contraindicated in pregnancy, the combination of hydralazine plus nitrate (isosorbide dinitrate) is the vasodilator therapy of choice during pregnancy. Hydralazine has been used for many years in the treatment of hypertension during pregnancy and appears to be safe for both the mother and fetus [5,29,30].
The combination of hydralazine plus nitrate (isosorbide dinitrate) is the vasodilator therapy of choice in pregnant patients with HF [7,10]. The evidence for hydralazine plus nitrate therapy for HFrEF is not as strong as the evidence for ACE inhibitor therapy. Therefore, we suggest that hydralazine not be routinely started when ACE inhibitor, ARB, or ARNI therapy is discontinued in patients who are clinically stable and normotensive. Hydralazine plus nitrate therapy should be used instead of ACE inhibitors, ARBs, or ARNI in pregnant patients with HF who are hypertensive, have severe LV systolic dysfunction, or have evidence of congestion and decompensated HF.
Limited data on breast milk and breastfed infant serum levels suggest that use of hydralazine is acceptable in nursing mothers [19]. Evidence is lacking on use of isosorbide dinitrate during breastfeeding. Since we usually restart ACE inhibitor therapy postpartum, we seldom use hydralazine plus nitrate to treat HF in nursing mothers.
Intravenous agents — A separate issue is the use of intravenous vasodilators (eg, nitroglycerin and nitroprusside) in pregnant patients with decompensated HF, particularly if associated with hypertension. Intravenous afterload reduction should be undertaken with great care in this setting given the risk of deterioration of the fetal heart rate with rapid and profound drop in maternal blood pressure. Continuous fetal monitoring is recommended if viability has been achieved.
Nitroglycerin or nitroprusside — In pregnant patients with decompensated HF, particularly those with hypertension, cautious use of intravenous nitroglycerin can be attempted [31]. A need for pronounced afterload reduction is a reason to consider nitroprusside rather than nitroglycerin. Examples of such settings include hypertensive emergency, acute aortic regurgitation, acute mitral regurgitation, aortic dissection, or acute ventricular septal defect. However, nitroprusside should be used only when all other interventions have failed and when it is essential for maternal well–being. Even under these conditions, the dose and duration of therapy should be minimized due to the metabolism of this agent to thiocyanate and cyanide, which has resulted in fetal cyanide poisoning in animal models [32]. Experience with nitroglycerin and nitroprusside in pregnant patients comes largely from treatment of hypertensive emergencies. (See "Drugs used for the treatment of hypertensive emergencies", section on 'Nitroprusside' and "Treatment of hypertension in pregnant and postpartum patients", section on 'Nitroprusside' and "Treatment of acute decompensated heart failure: Specific therapies".)
Since thiocyanate is excreted into breast milk and cyanide may also enter breast milk, nursing should be avoided if nitroprusside therapy is required [19]. Since intravenous use of nitroglycerin has not been studied during breastfeeding [19], nursing should be avoided when intravenous nitroglycerin is used.
Inotropes — Patients with acute decompensated HF and systolic dysfunction who are hypotensive or who remain in pulmonary edema despite oxygen, diuresis, and, if tolerated, vasodilators, may benefit from intravenous inotropic support. As each of these medications has slightly different properties, in a seriously ill pregnant woman, the selection of a specific agent should be based upon the clinical scenario. (See "Inotropic agents in heart failure with reduced ejection fraction".)
Dobutamine is a beta agonist with both inotropic and vasodilator properties. Dopamine has an inotropic effect and variable effects on the peripheral vasculature, depending upon the dose administered. Like dobutamine, the phosphodiesterase inhibitors such as milrinone have vasodilatory properties. Drugs with both inotropic and vasodilatory properties address the two hemodynamic problems that most commonly lead to low cardiac output in severe HF (ie, poor cardiac contractility, peripheral vasoconstriction).
No information is available on the use of dopamine or dobutamine during breastfeeding [19]. Intravenous dopamine infusion may decrease milk production, but this has not been directly studied.
Vasopressors — Vasopressors (eg, norepinephrine and phenylephrine) are usually avoided in patients with HF, since such patients usually have high systemic vascular resistance at baseline and further peripheral vasoconstriction may impair cardiac output. In pregnant patients, vasopressors carry the additional risk of impairing uterine blood flow. In critically ill, hypotensive patients, however, blood pressure may need to be supported. There are few data to guide selection of an appropriate vasopressor in a pregnant woman. Animal studies suggest that dopamine may have less deleterious effects on uterine blood flow than norepinephrine or phenylephrine. (See "Critical illness during pregnancy and the peripartum period", section on 'Vasopressors'.)
No information is available on the use of dopamine, norepinephrine, or phenylephrine during breastfeeding [19]. These drugs may decrease milk production.
Anticoagulants — The role of anticoagulation to manage thromboembolic risk in pregnant patients with HF is uncertain. Both pregnancy and HF are independently associated with an increased risk of thromboembolic phenomena. Venous thromboembolism complicates between 1 in 500 and 1 in 2000 pregnancies and is more common postpartum than antepartum [33,34]. This tendency probably reflects the hypercoagulable state of pregnancy. (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment".)
Indications for anticoagulation in patients with HF during pregnancy include systemic embolism or presence of a mechanical prosthetic heart valve. HF and/or low ejection fraction is not generally accepted as an indication for anticoagulation. This approach to patients who are pregnant is consistent with our approach to nonpregnant patients. (See "Antithrombotic therapy in patients with heart failure".)
However, the 2018 European Society of Cardiology guidelines suggest that anticoagulation may have role in patients who are pregnant with HFrEF; this recommendation is based on limited evidence [7,10].
Choosing a specific anticoagulation regimen for a pregnant or breastfeeding woman is challenging due to the potential teratogenic effects and dosing complexities of the various agents. These issues are discussed in detail separately. (See "Use of anticoagulants during pregnancy and postpartum".)
DELIVERY — Management of delivery in patients with heart disease is discussed separately. (See "Acquired heart disease and pregnancy", section on 'Management of labor and delivery'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of cardiovascular diseases during pregnancy" and "Society guideline links: Heart failure in adults".)
SUMMARY AND RECOMMENDATIONS
●Evaluation of heart failure during pregnancy
•Patients with a history of heart failure (HF) or cardiac disorders that put them at risk for HF should undergo a thorough initial evaluation prior to or in the early stage of pregnancy. (See 'Evaluation' above.)
•Patients who develop signs or symptoms of HF during pregnancy should undergo an initial evaluation similar to that generally recommended for patients with suspected HF. B-type natriuretic peptide (BNP) level may be helpful for risk stratification or if the diagnosis of HF is uncertain. A chest radiograph is not necessary to make the diagnosis of HF. (See 'New or acute heart failure' above and "Heart failure: Clinical manifestations and diagnosis in adults".)
●Counseling – Management of a woman with HF (or at risk for HF) contemplating pregnancy includes counseling the patient regarding the expected prognosis and potential risks of pregnancy. The discussion should be based upon an individualized assessment of risk utilizing the modified World Health Organization classification of maternal cardiovascular risk. Counseling should ideally occur prior to pregnancy. (See 'Counseling' above.)
●Treatment regimens – Patients with HF during pregnancy should be treated according to current major society guidelines for HF generally, except for avoiding contraindicated medications such as angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. We also suggest avoiding use of ivabradine during pregnancy, given lack of evidence of safety during pregnancy. For similar reasons, we suggest avoiding sodium-glucose co-transporter 2 (SGLT2) inhibitors. (See 'Chronic heart failure' above.)
•Drugs used to treat chronic HF with reduced ejection fraction (HFrEF) during pregnancy include diuretics, beta blockers, hydralazine plus nitrate, and digoxin. (See 'Drugs' above.)
-During pregnancy, clinical HF including pulmonary congestion is treated with a diuretic. (See 'Diuretics' above and "Use of diuretics in patients with heart failure".)
-Beta blockers are generally continued during pregnancy in patients with chronic HFrEF who are taking a beta blocker as part of a chronic regimen to improve long-term outcomes. (See 'Beta blockers' above.)
-For pregnant patients with symptoms of HF, hydralazine plus isosorbide dinitrate is a reasonable alternative to vasodilators contraindicated in pregnancy. (See 'Vasodilators' above.)
-For pregnant patients with symptoms of HF due to systolic dysfunction that persist despite diuresis and vasodilator therapy, digoxin can be used to treat symptoms. (See 'Digoxin' above.)
•Acute decompensated HF during pregnancy is managed with supplemental oxygen therapy and pharmacologic therapy (including diuretic therapy in patients with clinical HF including those with pulmonary edema). (See 'Acute heart failure' above and "Treatment of acute decompensated heart failure: Specific therapies".)
-For pregnant patients with severe decompensated HF and stable or elevated blood pressure, we suggest the addition of intravenous vasodilator therapy with nitroglycerin to the medical regimen (Grade 2C). In selected cases, the cautious use of nitroprusside may be an appropriate alternative to nitroglycerin. Hemodynamic and fetal monitoring should be employed, as appropriate. (See 'Vasodilators' above and "Treatment of acute decompensated heart failure: Specific therapies", section on 'Vasodilator therapy'.)
-Beta blocker therapy in pregnant patients with acute decompensated HFrEF is managed in the same manner as in nonpregnant patients with decompensated HF. Beta blockers are not initiated in the setting of acute decompensated HFrEF. Similarly, patients on chronic beta blocker therapy who develop acute decompensated HF often have the dose reduced or therapy withheld during initial treatment. (See 'Beta blockers' above and "Treatment of acute decompensated heart failure: General considerations".)
-Pregnant patients with severe decompensated HFrEF and hypotension may benefit from intravenous inotropic therapy. (See 'Inotropes' above and "Inotropic agents in heart failure with reduced ejection fraction".)
•Treatment of HF with preserved ejection fraction (HFpEF) during pregnancy remains empiric and includes control of systolic and diastolic hypertension, control of pulmonary congestion and peripheral edema with diuretics, and control of heart rate if elevated.
-Antihypertensive agents that may be used to treat HFpEF during pregnancy include beta blockers and heart rate limiting calcium channel blockers.
-Digoxin is not indicated in patients with HFpEF.
•For patients with refractory HF, specialized strategies include intravenous inotropic therapy, mechanical circulatory support (eg, left ventricular [LV] assist device), and cardiac transplantation. Limited data are available on LV assist device use during pregnancy. Cardiac transplant recipients are generally advised to avoid pregnancy during the first year posttransplantation when the risk of rejection is greatest and immunosuppressive therapy most aggressive. (See "Heart transplantation in adults: Pregnancy after transplantation".)
●Drugs to avoid during pregnancy – Drugs that should not be used in patients who are pregnant or who are planning to become pregnant include:
•ACE inhibitors, ARBs, and sacubitril-valsartan (see 'Avoid angiotensin inhibition' above)
•Mineralocorticoid receptor antagonists (see 'Aldosterone antagonists' above)
•SGLT2 inhibitors (see 'Sodium-glucose co-transporter 2 inhibitors' above)
•Ivabradine (see 'Ivabradine' above)
•Vericiguat (see 'Vericiguat' above)
●Anticoagulation – Indications for anticoagulation in patients with HF during pregnancy include standard indications for anticoagulation, such as evidence of systemic embolism or presence of a mechanical prosthetic heart valve. HF and/or low ejection fraction are not an indication for anticoagulation. (See 'Anticoagulants' above.)
