Introduction

Managing heart failure (HF) during pregnancy and breastfeeding presents unique challenges due to physiological changes that can exacerbate HF symptoms. Increased blood volume and cardiac output, particularly in the late second and early third trimesters, can place additional strain on the heart. For pregnant patients with pre-existing HF, or those with new-onset HF during pregnancy, these changes necessitate careful adjustments in management.^1,2 The primary goal is to maintain cardiac stability in the birthing parent while minimizing fetal risk, requiring a careful balance of medications to effectively control HF symptoms without adversely affecting fetal development.

Medication Use in Pregnancy

1. Angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), and angiotensin receptor–neprilysin inhibitors (ARNIs).^1-4
   1. Contraindicated due to risk of fetal kidney and skeletal abnormalities, growth restriction, and other complications.
2. Beta-blockers.^1-5
   1. Labetalol, carvedilol, propranolol, and metoprolol. Safe during pregnancy.
   2. Bisoprolol. Limited safety data compared with other agents.
   3. Atenolol. Avoid due to associations with fetal growth restriction, fetal bradycardia, and hypoglycemia.
3. Mineralocorticoid-receptor antagonists (MRAs)/aldosterone antagonists.^1-4
   1. MRAs. Avoid due to fetal antiandrogenic effects.
4. Sodium glucose cotransporter-2 inhibitors (SGLT2is).^1-4,6
   1. Avoid due to insufficient data on safety during pregnancy. Some data from animal studies suggest impact on fetal growth.
5. Hydralazine and nitrates.^1-4
   1. Hydralazine. Safe in pregnancy, although there are limited safety data.
   2. Nitrates. Use with caution because there are limited safety data in pregnancy.
      Note: Combinations of hydralazine/nitrates are typically vasodilators of choice in HF with reduced or preserved ejection fraction (after addition of labetalol and nifedipine).
6. Diuretics.^1,2,4
   1. Loop diuretics. Generally safe for use and are the preferred class of diuretics. Overuse may cause dehydration and electrolyte imbalances.
   2. Thiazide diuretics. Limited safety data and should be used with caution.
7. Adjunct therapies.
   1. Glucagon-like peptide-1 (GLP-1) agonists.⁶ Avoid due to insufficient safety data during pregnancy. Results of limited preliminary studies suggest risk of cardiac/congenital malformation with use of GLP-1 agonists or insulin.
   2. Vericiguat.⁷ Avoid during pregnancy. Preliminary assessments in animals showed maternal use was associated with fetal malformations and spontaneous abortion.
   3. Ivabradine.⁴ Avoid during pregnancy. Limited data; animal studies noted fetal harm associated with maternal use.
   4. Digoxin.^1,2,4 Generally safe; dosing may require adjustment during pregnancy.
8. Inotropes and other vasodilators.
   1. Inotropes (milrinone, dobutamine, and dopamine).^1,2 Reasonable to consider in severe HF if the benefits outweigh the potential risks, despite limited data supporting use.
   2. Nitroprusside. Avoid due to potential risk of fetal cyanide toxicity. If intravenous (IV) afterload reduction is required, consider nicardipine or hydralazine as alternatives.
   3. Nitroglycerin. Caution advised because limited data are available. IV nitroglycerin is recommended for use in pregnant patients with pre-eclampsia when severe hypertension is associated with pulmonary edema/acute decompensation. Of note, IV formulations may result in cervico-uterine relaxation.

Medication Use During Breastfeeding

1. ACEis, ARBs, and ARNIs.^1-5,8
   1. ACEis (enalapril, benazepril, and captopril). Safe during breastfeeding because they appear in low levels in breast milk and have poor oral bioavailability in infants.
   2. ARBs and ARNIs. Caution advised because limited data are available. Some data suggest candesartan and ARNIs may be safe with minimal transfer to breast milk, although they are not yet recommended for use by the manufacturers.
2. Beta-blockers.^1-5
   1. Labetalol, carvedilol, and metoprolol. Safe during breastfeeding.
   2. Bisoprolol. Can pass into breast milk and cause effects in infants, although unlikely at typical birthing parent doses. Recommend caution with preference given to other beta-blockers.
   3. Atenolol. Avoid due to higher levels in breast milk and potential effects on infants, including neonatal hypotension, tachypnea, cyanosis, and hypothermia.
3. MRAs/aldosterone antagonists.^1-4,9
   1. Spironolactone. Safe during breastfeeding.
   2. Eplerenone. Limited data, but some evidence exists that it is minimally secreted into breast milk. Use with caution.
   3. Finerenone. Avoid due to insufficient safety data during breastfeeding.
4. SGLT2is.^1-4,6
   1. Avoid due to insufficient data on safety during breastfeeding.
5. Hydralazine and nitrates.^1-4
   1. Hydralazine. Safe during breastfeeding; minimal secretion into breast milk.
   2. Nitrates. Limited data on use during breastfeeding, although generally thought to be safe when used with caution.
6. Diuretics.^1,2,4
   1. Loop diuretics. Considered safe and are the preferred diuretic class if needed. High doses can reduce milk production.
   2. Thiazide diuretics. Limited safety data available compared with other agents; use with caution.
7. Adjunct therapies.
   1. GLP-1 agonists.^6,10 Avoid during breastfeeding due to lack of safety data, although some preliminary evidence suggest minimal secretion into breast milk.
   2. Vericiguat.⁷ Avoid during breastfeeding due to lack of safety data.
   3. Ivabradine.⁴ Avoid during breastfeeding due to lack of safety data.
   4. Digoxin.^1,2,4 Safe during breastfeeding with minimal secretion into breast milk.
8. Inotropes and other vasodilators.
   1. Inotropes (milrinone, dobutamine, and dopamine).^1,2 Reasonable to consider in severe HF if the benefits outweigh the potential risks, despite limited data. Dopamine may decrease breast milk production.
   2. Nitroprusside. Avoid during breastfeeding because metabolites can be excreted into breast milk, which can act as a direct neonatal toxin and risk development of hypothyroidism. If IV afterload reduction is required, consider nicardipine or hydralazine, which are considered safe during breastfeeding.
   3. Nitroglycerin. Avoid during breastfeeding due to lack of safety data.

Conclusion

Managing HF during pregnancy and breastfeeding demands a nuanced and individualized approach, balancing the potential risks and benefits of medication use. Treatment plans should be customized to prioritize the safety of both the birthing parent and the fetus/neonate/infant. Although certain medications are contraindicated, others may be safely administered with careful monitoring (Table 1). As medical research expands the arsenal of HF therapies, engaging in discussions between patients and providers is essential because preliminary evidence often recommends caution or avoidance of medications in pregnancy/lactation. Additional research into cardiac disease in pregnancy and subsequent updates to clinical guidelines are vital in refining clinical understanding of the safest and most effective management strategies for HF in these unique populations. Effective collaboration among health care providers and informed decision-making by patients are crucial to achieving successful outcomes.

Table 1: HF Medication Recommendations in Pregnancy and Breastfeeding

^a Monitor for electrolyte derangements and dehydration
^b Monitor for decreased breast milk production
^c Benefits outweigh risks
ACEIs = angiotensin-converting enzyme inhibitors; ARBs = angiotensin-receptor blockers; ARNIs = angiotensin receptor–neprilysin inhibitors; GLP-1 = glucagon-like peptide-1; IV = intravenous; MRAs = mineralocorticoid-receptor antagonists; SGLT2is = sodium glucose cotransporter-2 inhibitors.

References

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