Cardiac Transplantation for Peripartum Cardiomyopathy in a Patient With Sickle Cell Disease

Abstract

Background

Cardiac surgery, particularly cardiac transplantation, is considered high risk in patients with sickle cell hemoglobinopathies and rarely reported in the literature.

Case Summary

We present a case of a 33-year-old woman with sickle cell β+ thalassemia and peripartum cardiomyopathy, who presented with sickling crisis and cardiogenic shock requiring temporary mechanical support. The patient ultimately successfully underwent heart transplantation.

Discussion

This case illustrates how careful use of mechanical circulatory support, appropriate perisurgical planning including preoperative exchange transfusion and avoidance of hypothermia, allowed for successful orthotopic heart transplantation in a woman with sickle cell hemoglobinopathy and cardiogenic shock in the postpartum setting.

Take-Home Messages

Cardiac transplantation in patients with hemoglobinopathies is rare but achievable. A tailored perioperative approach, developed by a collaborative multidisciplinary team, can optimize outcomes and lead to successful transplantation in these complex cases.

Graphical Abstract

History of Presentation: How the Patient Was Admitted and Physical Examination

A 33-year-old Black woman with sickle cell β+ thalassemia (Sβ+) presented to our emergency department with acute dyspnea and severe chest, back, and hip pain, described as being similar to a previous sickle cell crisis. She appeared restless. Her temperature was 37.2 °C, blood pressure was 109/80 mm Hg, respiratory rate was 22 breaths/min, oxygen saturation on pulse oximetry was 83% on room air, and heart rate was 116 beats/min. Her physical examination was notable for pulmonary rales and cold distal extremities.

Take-Home Messages

• •This case highlights the challenges with managing acute cardiopulmonary failure in sickle cell disease and stresses the importance of meticulous hemodynamic assessment, judicious use of temporary mechanical support, and thoughtful consideration of advanced cardiac therapies.
• •A multidisciplinary approach with a tailored perioperative strategy that minimizes hemolysis, maintains hemodynamic stability, and avoids hypothermia during cardiopulmonary bypass can allow for successful heart transplantation in sickle cell patients.

Past Medical History

Medical history was significant for childhood asthma, hypertension, and Hb S/β-thalassemia heterozygote sickle cell disease (SCD) (heterozygous positive for the hemoglobin S (Hb S) [c.20a>t] and c.-79a>g pathogenic variants in the beta globin gene) complicated by 2 prior vaso-occlusive crises (VOCs) and bilateral avascular hip necrosis. Three months before the current presentation, she had given birth to her second child in the setting of COVID-19 pneumonia and further complicated by painful VOCs and newly diagnosed heart failure with reduced ejection fraction to 35% consistent with peripartum cardiomyopathy. She had since been on low doses of guideline-directed medical therapy including sacubitril/valsartan, carvedilol, and spironolactone.

Differential Diagnosis

This patient's acute presentation raises several differential diagnoses including VOC with acute chest syndrome, pneumonia with hypoxic respiratory failure, acute decompensated heart failure with reduced ejection fraction, pulmonary embolism, or a combination of the aforementioned.

Investigations

Electrocardiogram results revealed sinus tachycardia (Figure 1). Transthoracic echocardiography depicted severe left ventricular systolic dysfunction with a left ventricular ejection fraction of 15%, a left ventricular end-diastolic diameter of 5.0 cm, and normal right ventricular function (Figure 2). Chest radiograph was consistent with increased vascular congestion. Computed tomography chest/pulmonary embolism study showed pulmonary edema, but no evidence of pulmonary embolism. Laboratory studies revealed microcytic anemia (hemoglobin [Hb]: 8.5 g/dL; baseline: 10-12), a platelet count of 91 k/μL (reference: 150-400), reticulocyte count of 4.0% (reference: 0.8-2.2), elevated plasma-free Hb of 42 mg/dL (reference: <10), haptoglobin of <10 mg/dL (reference: 30-200), an elevated lactic dehydrogenase of 1316 U/L (reference: 120-240), lactic acid of 2.6 mmol/L (reference: <2.5), creatinine of 0.84 mg/dL (reference: <1.20), alanine aminotransferase of 28 U/L (reference: <30), aspartate aminotransferase of 98 U/L (reference: <40), and total bilirubin of 1.6 mg/dL (reference: <1.2). A peripheral smear showed dacrocytes (teardrop cells) along with a decreased platelet estimate. Infectious work-up with blood cultures, respiratory pathogen panel, and urine antigen tests for Legionella pneumophila, due to its regional relevance in New York, and Streptococcus pneumonia, a common cause of severe community-acquired pneumonia, were negative.

Figure 1.

Admission Electrocardiogram

Electrocardiogram demonstrating sinus tachycardia at admission.

Figure 2.

Initial Transthoracic Echocardiography on Presentation

(A) Parasternal long-axis view and (B) 4-chamber view. Severe diffuse left ventricular hypokinesis, severely decreased left ventricular ejection fraction of 15%, and left ventricular end-diastolic diameter of 5.0 cm with normal right ventricular function are shown.

Within hours of initial presentation, the patient clinically deteriorated with increasing lethargy, weakness, persistently cold extremities, declining blood pressure to 70/44 mm Hg, and elevated creatinine (1.84 mg/dL), transaminases (alanine aminotransferase: 62 U/L; aspartate aminotransferase: 204 U/L), and total bilirubin (1.8 mg/dL), indicating shock, that is hypotension with end-organ dysfunction. To further evaluate her hemodynamic profile and guide management, a pulmonary artery catheter was placed. Right heart catheterization revealed severely elevated biventricular filling pressures and low cardiac output (Table 1).

Table 1.

Hemodynamic Data During Right Heart Catheterization

	Resultsa
Heart rate, beats/min	129
SBP/DBP/MAP, mm Hg	115/80/94
RAP, mm Hg	14
RVP, mm Hg	35/14
s/d/mPAP, mm Hg	35/25/29
PCWP, mm Hg	25
Fick CO, L/min	3.4
Fick CI, L/min/m2	1.7
PVR, WU	1.2
SVR, dynes·s·cm−5	2,141
PAPi	0.7
RVSWI	0.2

CI = cardiac index; DBP = diastolic blood pressure; Fick CO= Fick cardiac output; MAP = mean arterial pressure; PAPi = pulmonary artery pulsatility index; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RAP = right atrial pressure; RVP = right ventricular pressure; RVSWI = right ventricular stroke work index; s/d/mPAP = systolic/diastolic/mean pulmonary arterial pressure; SBP= systolic blood pressure; SVR = systemic vascular resistance; WU = Woods units.

^aRight heart hemodynamics were measured on dobutamine 2.5 μg/kg/min.

Management (Medical/Interventions)

Due to clinical concern for cardiogenic shock, the patient was started on dobutamine 2.5 μg/kg/min for circulatory support and noninvasive ventilation with bilevel positive airway pressure support even before right heart catheterization, confirming our suspicion. Subsequently, she required intubation for progressive hypoxemic respiratory failure and developed refractory hypotension despite 3 high-dose vasopressors, prompting venoarterial extracorporeal circulatory mechanical support (VA-ECMO) cannulation.

Persistent hemolysis (Hb: 7.5 g/dL; platelet count: 64 K/μL; lactic dehydrogenase: 1600 U/L; Hb S: 64.7%) led to the initiation of red cell exchange (RCE) transfusion, reducing Hb S to 17.0%. Over the next 72 hours, pressor requirements improved with return of pulsatility and improvement in oxygenation. After a successful trial of VA-ECMO flow reduction during decannulation readiness assessment, VA-ECMO was decannulated 5 days later¹; however, her biventricular function remained severely depressed. She continued to require intravenous inotropic support to maintain organ perfusion and was unable to tolerate any guideline-directed medical therapy for heart failure. Due to inotrope-dependent advanced heart failure, inability to tolerate guideline-directed medical therapy, and low likelihood of recovery, the care team initiated discussions around candidacy for heart replacement therapies.

Her hospital course was complicated by a subsegmental pulmonary embolism with concomitant pulmonary infarct noted on imaging. Given concerns for hemocompatibility-related adverse events with left ventricular assist devices in the setting of SCD, heart transplant was deemed the best option. Due to severe deconditioning, she required 8 weeks of inpatient rehabilitation to improve frailty before transplant listing. Once stable, she was listed as United Network for Organ Sharing status 3, and in anticipation of transplantation, an RCE transfusion was performed 48 hours before activating her on the transplant list, which yielded a Hb S of 15.7%, Hb of 12.1 g/dL, and hematocrit of 33%.

A suitable organ became available within 72 hours on the transplant list, likely due to the candidate's small size and favorable blood type. Although additional transfusions were planned to reduce Hb S to <10% during cardiopulmonary bypass (CPB) priming, hemodynamic instability during anesthesia induction necessitated emergent CPB initiation precluding further RCE to achieve Hb S <10%. Careful precautions were taken to avoid hypothermia during CPB to minimize the risk of sickling.

The patient successfully underwent transplantation with an ischemic time of 276 minutes, CPB time of 128 minutes, and cross-clamp time of 59 minutes. Posttransplant echocardiography showed near-normal biventricular function, and her postoperative recovery was unremarkable, with no rejection, infection, or hematologic complications.

Discussion: Association With Current Guidelines/Position Papers/Current Practice

We present a successful heart transplant case involving a 33-year-old woman with CS, sickling crisis, and underlying peripartum cardiomyopathy, and Sβ+.

SCD results from mutations in the β-globin gene, leading to the production of Hb S, which promotes sickling under stress conditions. In Sβ+, reduced but present production of normal hemoglobin (Hb A) generally results in a milder clinical course compared with more severe forms like Sβ0 thalassemia or homozygous hb S. Despite this, patients with Sβ+ remain at risk for complications,² particularly in the context of major surgeries. We identified only 4 case reports of heart transplants in adults with SCD/sickle cell trait (Supplemental Table 1), but none involving Sβ+, underscoring the unique nature of our case and the limited evidence available to guide management decisions. Considering these gaps in the literature, our case presented several clinical challenges that required careful consideration.

To begin with, the patient's presentation had multiple potential differential diagnoses and prompt right heart catheterization helped recognize and manage cardiogenic shock (CS) in a timely manner. Although it is unclear whether sickling or cardiac decompensation occurred first, we suspect that CS precipitated the sickling crisis. Hypoperfusion in SCD can cause erythrocytes to sickle, adhere to the endothelium, and trigger complement and coagulation cascades, leading to inflammatory response.³ This interplay creates a vicious cycle of worsening perfusion and increased sickling, further complicating hemodynamic stability (Figure 3). Additionally, although VA-ECMO is routinely used for CS, its use in patients with SCD is challenging due to exaggerated bleeding and clotting risks. During a VOC, platelets are hyperactive due to elevated cytokines (interleukin-1β and interleukin-6), and sickle cell-endothelial interactions activate coagulation, causing a disseminated intravascular coagulation-like state.⁴ Mechanical circulatory support, especially VA-ECMO, can amplify these hemostatic challenges.⁵ However, the severity of this young patient's refractory shock led our team to initiate VA-ECMO to support end organs, unload the heart, and allow time to reverse the sickling via RCE (Figure 3). Finally, cardiac transplantation in individuals with SCD or sickle cell trait is rare due to the risk of sickling crises triggered by factors associated with CPB (eg, hypothermia, hypoxia, hypoperfusion, acidosis).⁶ Hypothermia can be mitigated by using normothermic CPB and maintaining the circuit at 38 °C.⁷ Additionally, priming the CPB circuit with red blood cells, alongside crystalloids and colloids, helps maintain an optimal hematocrit. Although there is no consensus on safe Hb S levels for surgery, it is recommended to reduce Hb S to <30% for major procedures and even <5% for cardiac surgery, typically achieved through RCE before surgery.^7,8 However, performing full RCE at the time of transplant is often impractical due to medical complexities and the unpredictability of organ availability. Furthermore, blood typing and matching should consider antibodies against RhC, RhE, and Kell antigens.⁹ A key takeaway from our case is that exchange transfusion at the time of cardiac transplantation may not be feasible due to sudden hemodynamic instability on induction. Recognizing this challenge, we think that lowering Hb S levels before transplantation is highly advisable, despite the difficulty in predicting the exact timing of the procedure and the potential need for repeat exchange transfusion.

Figure 3.

Vaso-Occlusive Crisis and Cardiogenic Shock Overlap

Vicious cycle of worsening perfusion and increased sickling. Mechanical circulatory support is essential to support end organs and unload the heart while allowing time to reverse the sickling via red cell exchange. Hb = hemoglobin; MCS = mechanical circulatory support; RCE = red cell exchange.

In our patient's case, multidisciplinary coordination was central to both decision-making and perioperative management. Before listing for transplant, hematology and transfusion medicine developed and implemented RCE protocols to reduce Hb S to the target range of 10% to 20%. Cardiac anesthesia, surgery, and perfusion services worked in close collaboration to mitigate intraoperative hypothermia and to minimize vasopressor use and CPB duration. Heart failure, critical care, and pharmacy teams played a key role in optimizing the patient's hemodynamic status and managing early postoperative care.

This shared, team-based planning approach led to the successful execution of the transplant. The patient's history of mild Sβ+ disease and only 2 prior VOC episodes also contributed to the collective decision to proceed with transplantation.

Follow-Up

The patient had an uneventful postoperative course and was discharged to a rehabilitation center 22 days posttransplant. Her Hb S levels rose to her baseline of 50% to 60% over 2 to 3 months after transplant. At 2-year posttransplant follow-up, she remains well without any episodes of VOC, rejection, or cardiac allograft vasculopathy.

Conclusions

Mechanical circulatory support and heart transplantation can be viable options for select sickle cell patients with careful planning. This first reported heart transplant in an Sβ+ patient highlights the critical role of a multidisciplinary approach in overcoming the challenges of mechanical support and transplantation.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.