COVID-19 in Early Postoperative Heart Transplantation - Initial Experience

Covid-19/complications; Pandemics; Risk Factors; Severe Acute Respiratory Syndrome; Heart Transplantation; Imunossupression

Introduction

The coronavirus disease (COVID-19) pandemic is rapidly increasing worldwide. Brazil is the country with the second highest number of cases, and it is considered South America’s epicenter.¹

Cardiovascular disease is known to be an important risk factor for infection susceptibility, illness severity, and poor prognosis in COVID-19. Heart transplantation (HT) recipients may have an increased risk due to their comorbidities; however, it has been theorized that immunosuppression might protect them from the cytokine storm responsible for worse outcomes.²,³ On the other hand, infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in HT patients with disease presentation similar to general population, questioning the theorized immunosuppression protective mechanism.⁴-⁶

Herein, we present four cases of COVID-19 during the early postoperative (PO) HT period, with different short-term outcomes, including one death due to respiratory complications.

Case Reports

Case 1

A 51-year-old male patient, on PO day 50, presented chest pain with pleuritic characteristics. His chest computed tomography (CT) showed a ground glass pattern (Figure 1A), and was diagnosed with COVID-19 (Table 1). No specific treatment was required. Transthoracic echocardiography (TTE) showed normal (67%) left ventricle ejection fraction (LVEF). He was discharged home after receiving treatment for minor infectious complications related to immunosuppressive status.

Figure 1
– Chest computed tomography revealing peripheral ground glass opacities in case 1 (A), case 2 (B), case 3 (C) and case 4 (D).

Table 1
– Baseline characteristics and laboratory tests at the time of COVID-19 diagnosis

	Patient 1	Patient 2	Patient 3	Patient 4
Age (years)	55	22	48	31
Sex (male/female)	Male	Female	Male	Male
Heart disease etiology	Chagasic	Dilated	Chagasic	ARVC
INTERMACS	1	2	2	3
Preoperative condition	Inotropic + ECMO	Inotropic + IABP	Inotropic + IABP	Inotropic
Immunosuppression during COVID-19	Corticosteroids + Mycophenolate + Cyclosporine	Corticosteroids + Cyclosporine	Corticosteroids	Corticosteroids + Mycophenolate
LOS pre-HT (days)	14	80	58	143
Cold ischemia time (minutes)	212	261	146	161
LVEF PO HT (%)	67	60	63	65
PO COVID-19 diagnosis (days)	50	45	24	5
COVID-19 presentation	Mild	Moderate	Moderate	Severe

• ARVC: arrhythmogenic right ventricular cardiomyopathy; COVID-19: coronavirus disease 2019; ECMO: extracorporeal membrane oxygenation; HT: heart transplant; IABP: intra-aortic balloon pump; INTERMACS: Interagency Registry for Mechanically Assisted Circulatory Support; LOS: length of stay; LVEF: left ventricular ejection fraction; PO: postoperative.

Case 2

A 22-year-old female patient had primary graft dysfunction requiring extracorporeal membrane oxygenation (ECMO) for recovery. After weaning from ECMO on PO day 7, she presented fever that lead to COVID-19 diagnosis (Table 1). She required oxygen therapy, without mechanical ventilation or specific treatment. CT scan (Figure 1B) showed a ground glass pattern. The patient was discharged after anticoagulation due to minor pulmonary embolism. Last TTE showed 60% LVEF.

Case 3

A 48-year-old male patient, during hospitalization for decompensated heart failure, presented respiratory symptoms and chest CT suggestive of COVID-19; however, this was excluded after 3 negatives tests. Early PO was uneventful until PO day 21 (Figure 1C), when he presented fever and was diagnosed with COVID-19 (Table 1). Supplementary oxygen therapy was required, but not mechanical ventilation. The patient received azithromycin during his COVID-19 treatment. He was discharged with normal LVEF assessed by TTE (63%).

Case 4

A 31-year-old male patient, on PO day 5, presented cough and delirium. Chest CT showed ground glass images in both lungs (Figure 1C) and he tested positive for COVID-19 (Table 1). Supplementary oxygen therapy was needed, and he progressively got worse, requiring mechanical ventilation. The patient received azithromycin during his COVID-19 treatment. Last LVEF assessed by TTE was normal (65%). The patient died on PO day 12 due to acute respiratory failure.

Discussion

The pandemic of SARS-CoV-2 infection is dramatically increasing worldwide.¹ Elective surgeries have been cancelled and ward/ICU beds dedicated to pre- and postoperative care have been designated for patients with COVID-19. Cardiac surgeons and cardiologists are facing serious issues in making decisions to treat surgical patients in this period, since it is necessary to balance the risk of cardiovascular death due to delayed intervention, the risk of operating a patient in incubation or asymptomatic period of COVID-19 infection, and the risk of being infected during hospitalization after cardiac surgery.⁷

Concerning patients with heart failure, the challenge is even greater, because, due to cardiac decompensation, these patients frequently require long hospitalizations, which increase the risk of COVID-19. From 2010 to 2018, 44% of patients were hospitalized at the time of HT.⁸ During the pandemic, many HT centers are reassessing their waiting lists, prioritizing patients with lower life expectancy or hospitalized patients who have contraindications for durable left ventricular assist device (LVAD).⁹ Unfortunately, this strategy is not feasible for all centers due to a lack of resources, especially during the pandemic.

Our HT recipients include mostly hospitalized and prioritized patients, and durable LVAD was not possible. Most of our patients who underwent HT during the last 10 years were hospitalized at the time of HT. Despite all the preventive measures taken during hospitalization according to institutional protocols, these patients are at high risk of being infected by SARS-CoV-2.

According to the staging classification proposed by Siddiqi and Mehra, only one of our patients had severe COVID-19.¹⁰ The first three patients presented with mild and moderate forms, not requiring specific or intensive care treatment. Only two patients received azithromycin. The last patient died due to acute respiratory failure. Based on our limited experience and other published reports, COVID-19 may have similar presentation in HT recipients during the early PO phase (from mild to severe forms), whether compared to HT recipients in the late PO period or to the general population.⁴-⁶

To our knowledge, this case series is the first to report results in HT recipients developing COVID-19 during the early PO period, and our experience has shown similar disease presentations compared to non-HT recipients previously reported. Larger series are required to better understand this hypothesis. It currently seems that HT should be considered for patients who cannot be discharged home in centers where durable LVAD are not available, considering individual risks and benefits, weighed for each patient and local situation.

Referências

• ¹
  World Health Organization.(WHO). Coronavirus disease 2019 (COVID-19): situation report - 154. 2020. [Internet] [Cited in 2020 Jun23] Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200622-covid-19-sitrep-154.pdf?sfvrsn=d0249d8d_2
  » https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200622-covid-19-sitrep-154.pdf?sfvrsn=d0249d8d_2
• ²
  Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17:259-60.
• ³
  Aghagoli G, Gallo Marin B, Soliman LB, Sellke FW. Cardiac involvement in COVID-19 patients: Risk factors, predictors, and complications: A review. J Card Surg. 2020 Apr 19 . doi: https://doi.org/10.1111/jocs.14538
  » https://doi.org/10.1111/jocs.14538
• ⁴
  Li F, Cai J, Dong N. First cases of COVID-19 in heart transplantation from China. J Heart Lung Transplant. 2020;39(5);496-7.
• ⁵
  Holzhauser L, Lourenco L, Sarswat N, Kim G, Chung B, Nguyen AB. Early Experience of COVID-19 in Two Heart Transplant Recipients - Case Reports and Review of Treatment Options. Am J Transplant. 2020. 20(10):2916-22,
• ⁶
  Latif F, Farr MA, Clerkin KJ, Habal M, Takeda K, Naka Y, et al. Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease.JAMA Cardiol. 2020 May 13;e202159. Online ahead of print
• ⁷
  Haft JW, Atluri P, Alawadi G, Engelman D, Grand EM, Hassen A, et al. on behalf of the Society of Thoracic Surgeons COVID-19 Taskforce and the Workforce for Adult Cardiac and Vascular Surgery, Adult cardiac surgery during the COVID-19 Pandemic: A Tiered Patient Triage Guidance Statement. Ann Thorac Surg. 2020;110(2):697-700.
• ⁸
  International Society for Heart and Lung Transplantion. International Thoracic Organ Transplant (TTX) Registry Data - 2019. [Internet] [Cited in 2020 Jan 12] Available at https://ishltregistries.org/registries/slides.asp?year=2019
  » https://ishltregistries.org/registries/slides.asp?year=2019
• ⁹
  DeFilippis EM, Farr MA, Givertz MM. Challenges in Heart Transplantation in the Era of COVID-19. Circulation. 2020. 141(25):2048-61.
• ¹⁰
  Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states - A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5);405-7.

• Study Association
  This study is not associated with any thesis or dissertation.

• Sources of Funding.There was no external funding source for this study.

Publication Dates

• Publication in this collection
  03 Feb 2021
• Date of issue
  Jan 2021

History

• Received
  04 Aug 2020
• Reviewed
  09 Sept 2020
• Accepted
  09 Sept 2020