Peripartum Cardiomyopathy as the Initial Manifestation of Undiagnosed Sickle Cell Disease: A Case Report

Abstract

Peripartum cardiomyopathy (PPCM) occurring in the context of sickle cell disease (SCD) is exceedingly rare, particularly as the initial presentation of undiagnosed SCD. We report the case of a 39-year-old African primigravida at 36 weeks of gestation who presented with a 1-week history of heart failure symptoms. Her antenatal course was largely uneventful apart from severe anemia, for which she was transfused 2 units of whole blood followed by prescription of hematinics. Laboratory investigations revealed hemolytic anemia, a positive sickling test, and confirmatory hemoglobin electrophoresis demonstrating 93% sickle hemoglobin and 4.1% hemoglobin fetal, establishing a new diagnosis of homozygous SCD. Transthoracic echocardiography revealed a severely reduced left ventricular ejection fraction (LVEF 26%) and dilated left heart chambers, consistent with a diagnosis of PPCM. She was admitted to the maternity intensive care unit and managed by a multidisciplinary team, with stabilization on supportive therapy. At 38 weeks, she underwent a successful elective cesarean section, followed by an uneventful postpartum recovery. She was discharged 9 days postpartum in a stable condition (New York Heart Association Class II) on guideline-directed medical therapy and enrolled in outpatient follow-up. At 6 months, follow-up echocardiography showed partial recovery of cardiac function with an LVEF of 38%. She continues to be monitored by cardiology and hematology teams. This case highlights the critical importance of considering underlying hemoglobinopathies in pregnant patients presenting with unexplained heart failure, especially in regions where SCD is endemic.

Introduction

While access to medical care and public health interventions remains limited and uneven, sub-Saharan Africa (SSA) accounts for over three-quarters of global sickle cell disease (SCD) births, with up to 90% of affected infants dying before their fifth birthday.^{1 -4} With over one-fifth of the population carrying the sickle cell trait and 1.2% affected by the disease, Tanzania ranks as the fourth most prevalent nation for SCD worldwide, following Nigeria, the Democratic Republic of Congo, and India.^{5 -7} Generally, most SCD diagnoses are made in early childhood. However, in resource-constrained settings like SSA, limited newborn screening programs and inadequate diagnostic facilities pose significant challenges, resulting in some cases being diagnosed in adulthood, despite the high disease burden.^{8 -10}

The increased physiological demand for oxygen and nutrients during pregnancy exacerbates the underlying pathophysiology of SCD, posing substantial challenges for both the mother and fetus. A systematic review and meta-analysis has shown that pregnancies in women with the homozygous sickle cell disease (HbSS) genotype are associated with a 2- to 6-fold increased relative risk of preeclampsia, intrauterine growth restriction, preterm delivery, stillbirth, and maternal mortality compared to women without SCD. ¹¹ Furthermore, although cases of acute chest syndrome, sickle cell anemia, acute bone pain crises, and acute thoracic syndrome presenting during pregnancy as the initial manifestation of SCD have been documented, diagnosing SCD during pregnancy remains relatively uncommon.^{12 -16} Moreover, documented cases of peripartum cardiomyopathy (PPCM) occurring in SCD, let alone as the initial presentation of undiagnosed SCD, are exceedingly rare.^17,18 We report the case of a 39-year-old primigravida from Tanzania who presented with PPCM as the initial manifestation of previously undiagnosed SCD.

Case Description

A 39-year-old African primigravida at 36 weeks of gestation presented with a 1-week history of progressive easy fatigability, generalized edema, exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and nocturnal cough. Her antenatal course was largely uneventful until this episode, except for anemia (Hb 6.2 g/dL) diagnosed at 28 weeks of gestation during her first antenatal visit. She received 2 units of whole blood and was prescribed a 1-month course of hematinics (ferrous sulfate and folic acid). A follow-up visit was scheduled after 4 weeks, but she did not attend.

On examination, she was dyspneic at rest (New York Heart Association [NYHA] Class IV) with a respiratory rate of 31 breaths per minute, pulse rate of 133 beats per minute, blood pressure of 98/56 mmHg, and oxygen saturation of 91% on room air. She had marked bilateral pitting pedal edema, jugular venous distention, and bilateral basal crepitations. Cardiovascular examination revealed a laterally displaced apex beat at the sixth intercostal space along the anterior axillary line and an audible S3 gallop.

Laboratory evaluation revealed findings consistent with hemolytic anemia, including a hemoglobin level of 6.7 g/dL, elevated reticulocyte count (7.8%), hyperbilirubinemia (total bilirubin 3.5 mg/dL), and increased lactate dehydrogenase (710 U/L). Peripheral blood smear demonstrated sickled red blood cells. A sickling test was positive, and confirmatory prenatal hemoglobin electrophoresis revealed 93% sickle hemoglobin and 4.1% hemoglobin fetal, leading to a new diagnosis of HbSS. Echocardiography (ECHO) revealed a severely reduced left ventricular ejection fraction (LVEF 26%), dilated left heart chambers (left ventricular internal dimension in diastole 62.8 mm, left atrium diameter 46.9 mm), severe functional mitral and tricuspid regurgitation, moderate pulmonary hypertension (right ventricular systolic pressure 58 mmHg), and moderate pericardial effusion. These findings confirmed the diagnosis of PPCM.

Given the complexity of her condition, a multidisciplinary team comprising cardiology, hematology, and obstetric specialists was assembled in the national hospital setting. She was admitted to the maternity intensive care unit and initiated on supportive management, including propped-up positioning, oxygen supplementation, intravenous furosemide (60 mg twice daily), dopamine infusion (5 mcg/kg/min), metoprolol (50 mg daily), and transfusion with 2 units of packed red blood cells. The patient gradually improved, with stabilization of respiratory symptoms and hemodynamic parameters.

Due to persistent cardiac dysfunction, an elective cesarean section was performed at 38 weeks of gestation, resulting in favorable maternal and fetal outcomes. She was discharged 9 days postpartum in a stable condition (NYHA Class II) on guideline-directed medical therapy and scheduled for outpatient cardiology follow-up.

At 6 months postpartum, repeat ECHO demonstrated partial recovery of left ventricular function, with an LVEF of 38%. She remains under ongoing multidisciplinary follow-up with cardiology and hematology teams at the tertiary teaching hospital.

Discussion

SCD and PPCM are 2 distinct clinical entities that disproportionately affect individuals of African descent, with both conditions demonstrating higher prevalence in Black populations. The physiological demands of pregnancy particularly during the peripartum period when hemodynamic stress reaches its peak may unmask underlying cardiovascular or hematologic conditions such as SCD. Given their overlapping hematologic and cardiovascular complications, the coexistence of SCD and PPCM during pregnancy may result in severe, potentially life-threatening outcomes. Although literature directly linking the 2 conditions remains limited, shared pathophysiological features, including endothelial dysfunction, microvascular damage, hypercoagulability, increased thrombotic risk, and heightened cardiac workload, suggest a plausible interplay that could predispose women with SCD to the development of PPCM. ¹¹

The case we presented exhibited typical features of heart failure in pregnancy; however, further evaluation revealed hemolytic anemia and a positive sickling test, ultimately confirming previously undiagnosed SCD. Through chronic anemia, recurrent vaso-occlusive crises, and iron overload, SCD can impair myocardial perfusion and contribute to the development of PPCM. As each condition independently increases the risk of maternal and fetal morbidity and mortality, their coexistence may exert synergistic deleterious effects on the cardiovascular system, while also complicating both diagnosis and management. Given that multidisciplinary care involving cardiologists, hematologists, and obstetricians is essential for optimizing outcomes, early identification of underlying hemoglobinopathies is crucial to guide appropriate management, particularly in high-risk individuals.

Irrespective of the underlying etiology, sustained severe anemia can lead to a chronic high-output cardiac state characterized by compensatory tachycardia, increased stroke volume, and eventual cardiac chamber enlargement. ¹⁹ Patients with severe anemia may exhibit symptoms that overlap with those of PPCM, such as edema, elevated jugular venous pressure, dyspnea, and orthopnea. However, anemia-related high-output failure is typically characterized by preserved systolic function, in contrast to PPCM, which is marked by a significantly reduced ejection fraction. ²⁰ Although sustained anemia may have contributed to the clinical presentation in this case, the severe systolic dysfunction (EF 26%) combined with pronounced structural alterations is more consistent with PPCM than with anemia-related heart failure alone.

Considering the scarcity of documented cases, particularly PPCM in the context of undiagnosed SCD,^17,18 this case report adds to the limited body of literature and calls for increased awareness among healthcare providers. Furthermore, while this report suggests a potential interplay between SCD and PPCM, rigorous studies are needed to elucidate causality and inform the development of tailored clinical guidelines.

Conclusion

This rare case of PPCM as the initial presentation of previously undiagnosed SCD underscores the importance of maintaining a high index of suspicion for underlying hemoglobinopathies when evaluating heart failure in pregnancy, particularly in regions where SCD is endemic. As both PPCM and SCD independently contribute to adverse maternal and fetal outcomes, and may synergistically worsen prognosis, comprehensive multidisciplinary evaluation and timely integrated management are crucial to optimizing clinical outcomes and informing long-term care strategies.