Table of Contents Author Guidelines Submit a Manuscript
Case Reports in Obstetrics and Gynecology
Volume 2018, Article ID 8085649, 4 pages
https://doi.org/10.1155/2018/8085649
Case Report

Atrial Fibrillation as a Rare Complication of the Use of Nifedipine as a Tocolytic Agent: A Case Report and Review of the Literature

Department of Obstetrics and Gynecology, University of Toledo, Toledo, OH, USA

Correspondence should be addressed to Nikolina P. Docheva; ude.odelotu@avehcod.anilokin

Received 17 December 2017; Revised 9 March 2018; Accepted 5 April 2018; Published 15 May 2018

Academic Editor: Giampiero Capobianco

Copyright © 2018 Nikolina P. Docheva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Calcium channel blockers are commonly used tocolytic agents on Labor and Delivery units worldwide as part of the management of preterm labor. Despite their overall reassuring safety profile, rare cardiovascular complications have been reported. In this report, we describe the case of threatened preterm labor managed with nifedipine with subsequent development of atrial fibrillation. This type of cardiac arrhythmia may have considerable consequences for both the mother and the fetus. The aim of this case report and comprehensive review of the literature is to raise awareness.

1. Introduction

Normal maternal physiologic adaptations that occur during pregnancy can predispose to cardiac arrhythmias. Some of these adaptations are increased circulating blood volume and cardiac output with subsequent myocardial stretching, reduced systemic vascular resistance, modest decline in blood pressure, high plasma catecholamine concentrations, and adrenergic receptor sensitivity [15]. Studies have shown that the most common arrhythmias in pregnancy are ectopic premature contractions and nonsustained arrhythmias [6, 7]. Atrial fibrillation is rare in pregnancy with prevalence of 2 per 100,000 pregnancies and accounts for 1% of all hospital admissions for arrhythmia in the pregnant patient [7]. Most of the cases described in the literature occur in women with preexisting heart conditions such as congenital heart disease, hyperthyroidism, electrolyte disturbances, or the use of either recreational or prescribed drugs [810]. Atrial fibrillation, in the absence of structural heart disease or known cause, also known as “lone atrial fibrillation,” is even more rare [1016]. We present a case report of a patient without any structural cardiac defects who developed atrial fibrillation following the administration of nifedipine as a tocolytic agent.

2. Case Presentation

A 25-year-old African American woman, Gravida 7, Para 1, Aborta 5, presented at 29 weeks and 2 days with threatened preterm labor. The patient initially sought care at an outside facility where she received 0.25 mg of terbutaline SC for tocolysis and 12 mg IM of betamethasone for lung maturation. The patient was transferred to our tertiary facility with strong, regular uterine contractions. She underwent a transvaginal ultrasonogram which showed a normal cervical length of 3.4 cm. The patient was placed on continuous cardiotocographic monitoring and started on nifedipine (Procardia) 20 mg every 4 hours, with subsequent administration of the second dose of 12 mg IM betamethasone. Her pregnancy was complicated by opioid abuse, normocytic anemia (hemoglobin on admission 9.9 g/dL), and history of low transverse cesarean section for breech presentation. During the course of her hospitalization, she complained of heart palpitations and chest pain that radiated to her neck. On examination, her pulse palpated as irregularly irregular and vitals revealed a tachycardia into the 140 s. A twelve-lead ECG confirmed atrial fibrillation with rapid ventricular response. Cardiology was consulted. The patient was transferred to the intensive care unit and began on diltiazem drip and intravenous metoprolol for rate control. She received a total of six doses of nifedipine during her admission before discontinuation of the medication. Her symptoms occurred within 20 hours from the first dose of nifedipine. Work-up included an echocardiogram, lower extremities venous Doppler, troponin levels, thyroid function test, electrolytes, liver function tests, and a repeat urine drug test. All results were normal apart from borderline magnesium of 1.7 mg/dL (see Table 1 for further results). The patient converted to normal sinus rhythm in less than 24 hours with a CHA2DS2-VASc score of 1 and anticoagulation with 81 mg aspirin was started. After transfer out of the intensive care unit the patient remained in sinus rhythm for the remainder of the hospitalization. Discharge medications included metoprolol 25 mg twice daily for rate control with close outpatient follow-up with MFM and cardiology.

Table 1: Laboratory results.

The pregnancy culminated with a repeat low-transverse cesarean section at 39-week gestation resulting in a live-born male infant with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, and birthweight of 3400 grams. Continuous cardiac monitoring for 24 hours following delivery showed sinus rhythm. Per cardiology recommendations she was continued on metoprolol for prophylactic rate control and 81 mg aspirin in the postpartum period until she was seen as an outpatient. During that visit, metoprolol was discontinued.

3. Discussion

It is well known that atrial fibrillation predisposes to hemodynamic abnormalities and thromboembolic events leading to significant morbidity and mortality [17]. Pregnancy is a hypercoagulable state [18, 19] with an increased cardiac workload and therefore an increased susceptibility to arrhythmias [15]. Women with a history of any type of arrhythmia prior to pregnancy are at an increased risk of cardiac related morbidity, such as stroke and heart failure, during pregnancy [20]. However, because atrial fibrillation is rare in pregnancy, as are the sequela, it is difficult to adequately study the related adverse events. Lee et al. studied atrial fibrillation in pregnancy; of 264,730 pregnancies, atrial fibrillation was noted in only 157 [21]. The results suggest that older women (≥30 years of age) had higher odds of developing atrial fibrillation, and the odds significantly increased with increasing age [e.g., age 30–34 OR 4.1 95% CI (2.0–9.4), , and age ≥40 OR 5.2 95% CI (2.0–14.10), ]. They also reported an increased prevalence among White and Black women as compared to Asian and Hispanic patients (111.6, 101.7, 45.0, and 34.3 per 100,000, resp.). Moreover, the odds for atrial fibrillation were higher during the third trimester compared to the first trimester of pregnancy [3.2 95% CI (1.5–7.7), ]. In addition, there was no difference in birthweight among fetuses born to mothers with or without atrial fibrillation. However, the rate of admission to the neonatal intensive care unit was higher in the atrial fibrillation group (10.8% versus 5.1%  ) [21].

The case described here-in of threatened preterm labor depicts a common scenario seen in Labor and Delivery units worldwide. Preterm birth affects 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality [22]. Inhibition of uterine contractility with tocolytic agents is central to the treatment for preterm labor. Many different agents are available to inhibit uterine contractions including calcium channel blockers, magnesium sulfate, nonsteroidal anti-inflammatory drugs, beta-adrenergic receptor agonists, and oxytocin antagonists. The choice of a tocolytic agent is largely based on its contraindications. A recent systematic review and meta-analysis of randomized controlled trials ( women) showed that nifedipine was associated with a significant reduction in the risk of preterm delivery within 7 days of starting treatment, when initiated before 34-week gestation, compared with beta-adrenergic receptor agonists. The analysis also showed that there was no difference between the tocolytic efficacy of nifedipine and magnesium sulfate. However, nifedipine had significantly less maternal adverse events than magnesium sulfate and beta-adrenergic receptor agonists [23].

Nifedipine is a dihydropyridine calcium channel blocker that causes smooth muscle relaxation with vasodilatory action in the peripheral vasculature. There is a potential to provoke a compensatory adrenergic drive in order to maintain cardiac output, resulting in reflex tachycardia [24]. As previously mentioned the maternal physiologic adaptations of pregnancy predispose to arrhythmias and the additional effects of nifedipine on the maternal cardiovascular system can increase the risk of developing an arrhythmia. Despite the relatively safe profile of nifedipine, case reports have been published in the literature which described patients developing myocardial infarction [25, 26], severe hypotension leading to fetal demise [27], maternal hypoxia [28], and pulmonary edema associated with nifedipine [29, 30]. Moreover, a study showed cases of nifedipine-associated maternal dyspnea in patients with twin pregnancies underscoring a concern for administering nifedipine in women with compromised cardiovascular conditions which could be due to multiple gestation, maternal hypertension, cardiac disease, or intrauterine infection [24]. Our patient received a total of 6 doses of nifedipine 20 mg and we believe that this predisposed her to develop paroxysmal atrial fibrillation. In addition, she was anemic, further increasing the strain on the myocardium and potentiating the effects of the nifedipine. Parasuraman et al. [31] published the first case report in which a patient with threatened preterm labor was treated with nifedipine and developed atrial fibrillation that responded to DC cardioversion, whereas Cheung et al. [32] described a case of maternal atrial fibrillation after sequential use of nifedipine and atosiban for the treatment of preterm labor. de Heus et al. reported, in a multicenter prospective cohort study, that, among the 542 women treated with nifedipine, 5 (0.9%) had a serious adverse side effect and 6 (1.1%) had a mild adverse side effect [33]. In addition, Khan et al., in a systematic review and meta-regression analysis, evaluated the safety of nifedipine as a tocolytic agent in preterm labor and as an antihypertensive agent in the treatment of hypertension in pregnancy. The results showed that adverse events were the highest among women given more than 60 mg total dose of nifedipine [OR 3.78, 95% CI (1.27–11.2), ] and in reports from case series compared to controlled studies [OR 2.45, 95 CI (1.17–5.15), ] [34]. Outside pregnancy, short acting nifedipine has been associated with increased risk of myocardial infarction and mortality when used to treat hypertension. This is believed to be due to the hypotension and reflex tachycardia that can predispose to an arrhythmia [35]. The FDA states that atrial or ventricular dysrhythmias can occur in less than 1% of patients on short acting nifedipine [36].

This case report provides a lesson for physicians in the field of high risk obstetrics. Caution must be taken when administering tocolytic agents such as nifedipine. Even though the medication is overall safe and the aforementioned side effects are rare, there is a small subset of patients that develop severe side effects such as atrial fibrillation, which may lead to significant maternal and fetal morbidity.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

References

  1. W. M. Barron, S. K. Mujais, M. Zinaman, E. L. Bravo, and M. D. Lindheimer, “Plasma Catecholamine Responses to Physiologic Stimuli in Normal Human Pregnancy,” Obstetric Anesthesia Digest, vol. 154, no. 1, pp. 80–84, 1986. View at Publisher · View at Google Scholar
  2. J. H. McAnulty, M. J. Morton, and K. Ueland, “The heart and pregnancy,” Current Problems in Cardiology, vol. 13, no. 9, pp. 594–665, 1988. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Hunter and S. C. Robson, “Adaptation of the maternal heart in pregnancy,” British Heart Journal, vol. 68, no. 6, pp. 540–543, 1992. View at Publisher · View at Google Scholar · View at Scopus
  4. G. J. Gilson, S. Samaan, M. H. Crawford, C. R. Qualls, and L. B. Curet, “Changes in hemodynamics, ventricular remodeling, and ventricular contractility during normal pregnancy: a longitudinal study,” Obstetrics & Gynecology, vol. 89, no. 6, pp. 957–962, 1997. View at Publisher · View at Google Scholar · View at Scopus
  5. J. G. Ouzounian and U. Elkayam, “Physiologic changes during normal pregnancy and delivery,” Cardiology Clinics, vol. 30, no. 3, pp. 317–329, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Shotan, E. Ostrzega, A. Mehra, J. V. Johnson, and U. Elkayam, “Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope,” American Journal of Cardiology, vol. 79, no. 8, pp. 1061–1064, 1997. View at Publisher · View at Google Scholar · View at Scopus
  7. J.-M. Li, C. Nguyen, J. A. Joglar, M. H. Hamdan, and R. Page, “Frequency and outcome of arrhythmias complicating admission during pregnancy: Experience from a high-volume and ethnically-diverse obstetric service,” Clinical Cardiology, vol. 31, no. 11, pp. 538–541, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. P. Szekely and L. Snaith, “Atrial fibrillation and pregnancy,” British Medical Journal, vol. 1, no. 5237, pp. 1407–1410, 1961. View at Publisher · View at Google Scholar · View at Scopus
  9. L. T. A. Dicarlo-Meacham and L. J. Dahlke, “Atrial fibrillation in pregnancy,” Obstetrics & Gynecology, vol. 117, no. 2, pp. 489–492, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Sauvé, É. Rey, and A. Cumyn, “Atrial Fibrillation in a Structurally Normal Heart during Pregnancy: A Review of Cases From a Registry and From the Literature,” Journal of Obstetrics and Gynaecology Canada, vol. 39, no. 1, pp. 18–24, 2017. View at Publisher · View at Google Scholar · View at Scopus
  11. R. M. Gowda, G. Punukollu, I. A. Khan et al., “Lone atrial fibrillation during pregnancy [9],” International Journal of Cardiology, vol. 88, no. 1, pp. 123-124, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. K. M. Kuczkowski, “New onset transient lone atrial fibrillation in a healthy parturient: Déjà vu [9],” International Journal of Cardiology, vol. 97, no. 2, p. 339, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. C.-H. Lin and C.-N. Lee, “Atrial fibrillation with rapid ventricular response in pregnancy,” Taiwanese Journal of Obstetrics and Gynecology, vol. 47, no. 3, pp. 327–329, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. C. A. Walsh, T. Manias, and C. Patient, “Atrial fibrillation in pregnancy,” European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 138, no. 1, pp. 119-120, 2008. View at Publisher · View at Google Scholar
  15. L. Cacciotti, G. S. Camastra, and G. Ansalone, “Atrial fibrillation in a pregnant woman with a normal heart,” Internal and Emergency Medicine, vol. 5, no. 1, pp. 87-88, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. C. J. Sengheiser and K. C. Channer, “Recurrent atrial flutter and fibrillation in pregnancy,” BMJ Case Reports, vol. 2011, 2011. View at Google Scholar · View at Scopus
  17. C. T. January et al., “Correction to 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society,” Circulation, vol. 136, no. 16, pp. e269–e270, 2017. View at Publisher · View at Google Scholar
  18. K. A. Bremme, “Haemostatic changes in pregnancy,” Best Practice & Research Clinical Haematology, vol. 16, no. 2, pp. 153–168, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Franchini, “Haemostasis and pregnancy,” Thrombosis and Haemostasis, vol. 95, no. 3, pp. 401–413, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. S. C. Siu, M. Sermer, J. M. Colman et al., “Prospective multicenter study of pregnancy outcomes in women with heart disease,” Circulation, vol. 104, no. 5, pp. 515–521, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Lee, W. Chen, Z. Zhang et al., “Atrial Fibrillation and Atrial Flutter in Pregnant Women—A Population‐Based Study,” Journal of the American Heart Association, vol. 5, no. 4, p. e003182, 2016. View at Publisher · View at Google Scholar
  22. R. Romero, S. K. Dey, and S. J. Fisher, “Preterm labor: one syndrome, many causes,” Science, vol. 345, no. 6198, pp. 760–765, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Conde-Agudelo, R. Romero, and J. P. Kusanovic, “Nifedipine in the management of preterm labor: a systematic review and metaanalysis,” American Journal of Obstetrics & Gynecology, vol. 204, no. 2, pp. 134.e1–134.e20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. H. P. Van Geijn, J. E. Lenglet, and A. C. Bolte, “Nifedipine trials: Effectiveness and safety aspects,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 112, no. 1, pp. 79–83, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. S. G. Oei, S. K. Oei, and H. A. Brölmann, “Myocardial infarction during nifedipine therapy for preterm labor,” The New England Journal of Medicine, vol. 340, no. 2, p. 154, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Verhaert and R. van Acker, “Acute myocardial infarction during pregnancy,” Acta Cardiologica, vol. 59, no. 3, pp. 331–339, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. A. J. Van Veen, M. J. Pelinck, M. G. Van Pampus, and J. J. H. M. Erwich, “Severe hypotension and fetal death due to tocolysis with nifedipine,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 112, no. 4, pp. 509-510, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Hodges, A. Barkehall-Thomas, and C. Tippett, “Maternal hypoxia associated with nifedipine for threatened preterm labour,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 111, no. 4, pp. 380-381, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. O. M. Abbas, A. H. Nassar, N. A. Kanj, and I. M. Usta, “Acute pulmonary edema during tocolytic therapy with nifedipine,” American Journal of Obstetrics & Gynecology, vol. 195, no. 4, pp. e3–e4, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. M. S. Kutuk, M. T. Ozgun, S. Uludag, M. Dolanbay, and A. Yildirim, “Acute pulmonary failure due to pulmonary edema during tocolytic therapy with nifedipine,” Archives of Gynecology and Obstetrics, vol. 288, no. 4, pp. 953-954, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. R. Parasuraman, M. M. Gandhi, and N. H. Liversedge, “Nifedipine tocolysis associated atrial fibrillation responds to DC cardioversion,” BJOG: An International Journal of Obstetrics & Gynaecology, vol. 113, no. 7, pp. 844-845, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. C. S.-Y. Cheung, T. K.-T. Li, and C.-P. Lee, “Maternal atrial fibrillation after sequential use of nifedipine and atosiban for treatment of preterm labor: Case report,” European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 166, no. 2, p. 229, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. R. de Heus, B. W. Mol, J. H. Erwich et al., “Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study,” BMJ, vol. 338, no. mar05 2, pp. b744–b744, 2009. View at Publisher · View at Google Scholar
  34. K. Khan, J. Zamora, R. F. Lamont et al., “Safety concerns for the use of calcium channel blockers in pregnancy for the treatment of spontaneous preterm labour and hypertension: A systematic review and meta-regression analysis,” The Journal of Maternal-Fetal and Neonatal Medicine, vol. 23, no. 9, pp. 1030–1038, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. C. D. Furberg, B. M. Psaty, and J. V. Meyer, “Nifedipine: Dose-related increase in mortality in patients with coronary heart disease,” Circulation, vol. 92, no. 5, pp. 1326–1331, 1995. View at Publisher · View at Google Scholar · View at Scopus
  36. “PROCARDIA® (nifedipine) CAPSULES For Oral Use”.