Cardiac Transplant Patients at Higher Risk for COVID-19, Death

Multicenter data from northern Italy, one of the world’s hardest-hit regions in this year’s pandemic, show a doubling of COVID-19 prevalence and related mortality for patients with heart transplants.

“[This] should spur clinicians to immediately refer heart transplant recipients suspected as having SARS-CoV-2 infection to centers specializing in the care of this vulnerable population,” conclude Tomaso Bottio, MD, PhD (University of Padua, Italy), and colleagues in their paper published online today in JACC: Heart Failure. Notably, survival didn’t diverge according to whether patients had their immunosuppressive therapy reduced to deal with the challenges of the virus.

How COVID-19 manifests in people with heart transplants is among a swath of cardiovascular concerns sparked by the disease.

For transplant in particular, Mary Norine Walsh, MD (St. Vincent Hospital, Indianapolis, IN), commenting on the findings for TCTMD, drew parallels to a single-center New York-based report that came out in May in JAMA Cardiology. That earlier experience captured a similar case-fatality rate—around one-quarter of transplant patients infected with SARS-CoV-2—as well as similar breakdowns for gender and risk factors, she said.

Differences, however, are that Italy saw the pandemic arrive earlier than did the United States, Walsh pointed out, and that this latest data set drew from numerous centers.

It’s unsurprising that both reports observed an increased death rate for these immunosuppressed patients susceptible to infectious diseases in general, she continued. “The people who did more poorly had comorbid disease states, like renal failure.” Many also had cardiovascular histories like previous PCI and some degree of cardiac allograft vasculopathy (CAV) in their transplant, Walsh added.

Some things have evolved over the course of 2020, though, so Walsh specified that the Italian study is a “snapshot in time” reflecting earlier strategies. For example, more than 80% of the transplant patients received hydroxychloroquine, a drug that has not panned out as hoped. Other than reducing immunosuppressive therapy, she said, COVID-19 treatment is similar with or without transplant.

Case-Fatality Rate Nearly 30%

Across seven heart transplant centers in northern Italy, Bottio et al saw a total of 47 patients who tested positive for SARS-COV-2 from February to June 2020. Hospitalization was required for 38 patients (mean stay 17.79 days), of whom four were admitted to the ICU. Fourteen people (37%) died. Respiratory failure was the cause of death in all cases apart from one person who died from multiorgan failure.

For all hospitalized patients, the dose of immunosuppressive drugs was reduced. For the nine patients able to quarantine at home, just four (44%) continued their prior immunosuppressive regimen. Survival rates did not differ by immunosuppressive therapy use.

Overall COVID-19 prevalence was twice as high in the transplant patients compared with the general population in the region (18 vs 7 cases per 1,000), as was the COVID-19 case-fatality rate (29.7% vs 15.4%). Since July 1, 2020, the centers saw six new transplant recipients test positive for SARS-CoV-2: five were asymptomatic and self-quarantined, while one is hospitalized for pneumonia.

‘An Overwhelming Emergency’

The fact that COVID-19 prevalence was doubled in the transplant group “is likely the result of the higher susceptibility of heart transplant recipients to infections due to their chronic immunosuppressed state,” investigators say.

The heightened mortality, on the other hand, may be partly due to strained healthcare systems. Thirteen of the 38 hospitalized patients developed acute respiratory syndrome, with 15 (32%) and two (4%) requiring noninvasive and invasive ventilation, respectively. The death rate among patients with primarily pulmonary presentation reached 30%.

“These poor outcomes may be related to the rapidity with which the pandemic spread in northern Italy, leading to a critical shortage of ICU beds over a period of only a few days,” they write. “In these circumstances, heroic efforts were made to manage very ill patients in non–acute-care settings. It is plausible that lack of healthcare resources in the midst of an overwhelming emergency may have contributed to the high mortality rate of our patients’ cohort.”

What didn’t seem to affect death rates, however, was allograft dysfunction/rejection in the context of less immunosuppression, a strategy intended to aid the immune response against the virus and reduce the risk of superinfections in the hospital.

“For future hospitalized heart transplant recipients with COVID-19, our strategy will consist of reduction of immunosuppression and antibiotic prophylaxis, along with the best supportive care available. We believe that in the asymptomatic forms, immunosuppressive therapy may remain unchanged until the first symptoms emerge,” they say.

For Walsh, and for the authors, one caveat “is that they’re only reporting patients they knew were positive. They have no idea if there were asymptomatic positives in their population,” she said, adding, “The whole population hasn’t gotten tested yet, so there may be some asymptomatic [transplant] patients who do well.” Also unclear is how the sex distribution in this COVID-19 cohort compares against northern Italy’s transplant population as a whole, which Walsh said would’ve been interesting to know given that men tend to do worse with COVID.

Caring for transplant patients in the COVID-19 setting is something that comes up “frequently” in her practice, said Walsh. “I live in the Midwest and the COVID numbers are very high. Our hospital is full, as are other hospitals, and we have several cardiac transplant patients who are hospitalized with COVID.” Her strategies for treating these individuals matches up with what the Italian researchers suggest, she noted.

Knowledge gaps still need to be filled. “What we don’t know . . . in cardiac transplant patients is will there be any long-term effects on the graft—just like we’re not sure in the overall population of COVID patients what the sequelae of myocarditis may mean,” she noted. “We won’t know that for a long time.”