COVID-19 Mortality Higher Among Heart Transplant Patients

Batya Swift Yasgur MA, LSW

June 02, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020 and April 24, 2020 and found a case-fatality rate of 25%.

"The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic," senior author Nir Uriel, MD, MSc, professor of medicine, Columbia University Vagelos College of Physicians and Surgeons, New York City, told theheart.org | Medscape Cardiology.

"These patients require extra precautions to prevent the development of infection," said Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.

Similar Presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors write.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 [IQR, 53.5 - 70.5] years; 79% male) to "describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process."

The median time from HT to study period was 8.6 (IQR, 4.2 - 14.5) years. Most patients had numerous comorbidities.

Comorbidities Among Heart Transplant Patients
Condition n %
Hypertension 20 71
Diabetes mellitus 17 61
Obesity 7 25
Chronic kidney disease (stage IV or higher) 10 36
Cardiac allograft vasculopathy 16 57
Pre-existing allograft dysfunction 4 14

"The presentation of COVID-19 was similar to nontransplant patients with fever, dyspnea, cough, and GI [gastrointestinal] symptoms," Urlel reported.

No Protective Effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the intensive care unit (ICU) and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL [IQR, 7.44 - 19.26]; median peak interleukin [IL]-6, 105 pg/mL [IQR, 38 - 296]).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxycholoroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

"Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections," Uriel commented.

"With COVID-19, in which the body's inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect," he continued.

"This case series suggests that this is not the case, although this would need to be confirmed in larger studies," he said.

Low Threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center and five died in an outside institution.

"In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection," Uriel stated.

"In addition, we have restricted these patients' contact with the hospital as much as possible during the pandemic," he said.

However, "there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital," he added.

The authors emphasize that COVID-19 patients "will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent."

Vulnerable Population

Commenting on the study for theheart.org | Medscape Cardiology, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women's Hospital, Boston, suggested that "in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper."

Given that Columbia is "one of the larger heart transplant centers in the US, following probably 1000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate," said Mehra, who is also the executive director of the Center for Advanced Heart Disease, Brigham and Women's Hospital, and professor of medicine, Harvard Medical School.

"We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe," explained Mehra, who was not involved with the study.

Moreover, the patients were "older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart," so "it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability," he said.

Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

He acknowledged, however, that because these are patients with serious vulnerability due to underlying heart disease, "you can't be lackadaisical and need to do everything to decrease this vulnerability."

The authors note that although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Uriel reports no relevant financial relationships. The other authors' disclosures are listed in the publication. Mehra reports no relevant financial relationships.

JAMA Cardiol. Published online May 13, 2020. Full text

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