Retrospective Evaluation of COVID-19 Infection and COVID-19 Vaccines in Heart Transplant Patients.

BACKGROUND: Patients who have performed solid organ transplantation in terms of COVID-19 infection are included in the high-risk group. In this study, it was aimed to evaluate the relationship between vaccination and retrospective evaluation of 32 patients who underwent a heart transplant in the clinic and tested positive for SARS-CoV-2 polymerase chain reaction. METHODS: In this study, demographic characteristics of the cases, comorbidities, timing of heart transplantation, immunosuppressive treatments, symptoms of COVID-19 infection, lung imaging findings, follow-up (outpatient/inpatient), treatments, 1-month mortality, and vaccination histories against COVID-19 infection were evaluated. The data obtained from the study were analyzed with SPSS version 25.0. RESULTS: The 3 most common symptoms are cough (37.5%), myalgia (28.1%), and fever (21.8%). COVID-19 infection was severe in 6.2% of the patients, moderate in 37.5%, and mild in 56.2%. Hospitalization was required in 5 patients (15.6%, 1 in the intensive care unit), and the other patients were followed up as an outpatient. Severe COVID-19 infection was seen more in 33% of unvaccinated patients; 93.5% were vaccinated. Nineteen patients (68%) were vaccinated before COVID-19 infection. Our patients received the CoronoVac (Sinovac, China) vaccine. CONCLUSION: COVID-19 infection is more likely to be severe and mortal in patients with heart transplant recipients. It is also crucial to comply with preventive measures other than immunization in this group of patients. This study is the largest series investigating COVID-19 infection in heart transplant recipient patients in our country.

ST-segment elevation myocardial infarction as a COVID-19 manifestation in a recent heart transplant recipient.

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Accelerated Cardiac Allograft Vasculopathy in an Orthotopic Heart Transplant Recipient with Prior COVID-19.

BACKGROUND Cardiac allograft vasculopathy (CAV) is a post-orthotopic heart transplant (OHT) complication driven by intimal smooth muscle proliferation and immune hyperactivity to donor heart tissue. Accelerated CAV leads to allograft failure within 1 year after receiving a normal angiogram result. Viruses can contribute to CAV development, but CAV after SARS-CoV-2 infection has not been reported to date. CASE REPORT A 48-year-old man, 5 years after OHT for non-ischemic cardiomyopathy, was admitted to the Cardiac Care Unit with 3 days of abdominal pain, dyspnea, and palpitations. His medical history included hyperlipidemia and insulin-dependent diabetes. He was compliant with all medications. Two months prior, he had a mild COVID-19 case. An echocardiogram and coronary angiogram 6 and 9 months prior, respectively, were unremarkable. Right and left heart catheterization demonstrated increased filling pressures, a cardiac index of 1.7 L/ml/m², and diffuse vasculopathy most severe in the LAD artery. Flow could not be restored despite repeated ballooning and intra-catheter adenosine. Empiric ionotropic support, daily high-dose methylprednisolone, and plasmapheresis were started. A few days later, the patient had cardiac arrest requiring venoarterial extracorporeal membranous oxygenation. Given CAV's irreversibility, re-transplantation was considered, but the patient had an episode of large-volume hemoptysis and remained clinically unstable for transplant. The patient died while on palliative care. CONCLUSIONS Our patient developed accelerated CAV 2 months after having COVID-19. While CAV has known associations with certain viruses, its incidence after SARS-CoV-2 infection is unknown. Further research is needed to determine if prior SARS-CoV-2 infection is a risk factor for development of CAV in OHT recipients.

Real-world experience of tixagevimab-cilgavimab pre-exposure prophylaxis in orthotopic heart transplant recipients.

BACKGROUND: Pre-exposure prophylaxis with tixagevimab-cilgavimab (tix-cil) may be associated with cardiovascular adverse events. Also, in vitro studies have reported a reduced activity of tix-cil against emerging SARS-CoV-2 Omicron subvariants. Our study aimed to report the real-world outcomes of tix-cil prophylaxis in orthotopic heart transplant (OHT) recipients METHODS: We retrospectively studied all OHT recipients who received one dose of tix-cil (150-150 mg or 300-300 mg) at Mayo Clinic in Arizona, Florida, and Minnesota, between February 5, 2022 and September 8, 2022. We collected data on cardiovascular adverse events and breakthrough COVID-19 following tix-cil administration. RESULTS: One hundred sixty-three OHT recipients were included. The majority were male (65.6%), and the median age was 61 years (IQR 48, 69). During the median follow-up of 164 days (IQR 123, 190), one patient presented an episode of asymptomatic hypertensive urgency that was managed with outpatient antihypertensive treatment optimization. Twenty-four patients (14.7%) experienced breakthrough COVID-19 at the median of 63.5 days (IQR 28.3, 101.3) after tix-cil administration. The majority (70.8%) completed the primary vaccine series and received at least one booster dose (70.8%). Only one patient with breakthrough COVID-19 required hospitalization. All patients survived. CONCLUSIONS: In this cohort of OHT recipients, no patients developed severe cardiovascular events related to tix-cil. The high incidence of breakthrough COVID-19 could be due to the reduced activity of tix-cil against current circulating SARS-CoV-2 Omicron variants. These results emphasize the need for a multimodal prevention strategy against SARS-CoV-2 in these high-risk patients.

Improved immunogenicity following the third dose of BNT162b2 mRNA vaccine in heart transplant recipients.

OBJECTIVES: The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients. METHODS: This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14-28 days after the third dose. Titres above 50 U/ml were interpreted positive. RESULTS: We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58-70]. At baseline, the median of 27 days (IQR 13-42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4-130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7-6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre. CONCLUSIONS: Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.

Heart Transplantation from COVID-19-Positive Donors: A Word of Caution.

BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

Heart transplantation for COVID-19 myopathy in the United States.

Evidence on characteristics and outcomes of patients undergoing heart transplantation for coronavirus disease 2019 (COVID-19) associated cardiomyopathy is limited to case reports. Of all 6,332 patients aged ≥18 years undergoing heart transplantation from July 2020 through May 2022 in the United Network for Organ Sharing database, 12 (0.2%) patients had COVID-19 myocarditis and 98 (1.6%) patients with the same level of care had non-COVID-19 myocarditis. Their median age was 49 (range 19-74) years. All patients were hospitalized in the intensive care unit and 92.7% (n = 102) were on life support prior to transplantation. No patients with COVID-19 myocarditis required ventilation while waitlisted. Survival free from graft failure was 100% among COVID-19 patients and 88.5% among non-COVID-19 patients at a median of 257 (range 0-427) days post-transplant. These findings indicate that transplantation is rarely performed for COVID-19 related cardiomyopathy in the United States, yet early outcomes appear favorable in select patients.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

Treatment of Pediatric Patients With COVID Infection After Heart Transplantation.

The COVID-19 pandemic that has been ongoing since the beginning of 2020 has forced health care into a difficult struggle for wellness and the lives of patients. International data and our observations show that the course of the disease in these patients is different than in the general population. Symptoms depend on the immunosuppression and severity of viremia. The period of viral replication is much longer. Our observations include 4 pediatric patients post heart transplant who became infected with the coronavirus. One patient was infected in the hospital during perioperative period. Two others required hospitalization because of the severity of symptoms, and 1 was treated on an outpatient basis. The applied treatment included the reduction of immunosuppression, low-molecular-weight heparin, amantadine or remdesivir, steroids, and supplementation with zinc and vitamins C and D. Based on the antigenic tests performed, we determined the period of active replication to be 3 to 8 weeks from the onset of the first symptoms.

Patient selection for heart transplant: balancing risk.

PURPOSE OF REVIEW: Heart failure incidence continues to rise despite a relatively static number of available donor hearts. Selecting an appropriate heart transplant candidate requires evaluation of numerous factors to balance patient benefit while maximizing the utility of scarce donor hearts. Recent research has provided new insights into refining recipient risk assessment, providing additional tools to further define and balance risk when considering heart transplantation. RECENT FINDINGS: Recent publications have developed models to assist in risk stratifying potential heart transplant recipients based on cardiac and noncardiac factors. These studies provide additional tools to assist clinicians in balancing individual risk and benefit of heart transplantation in the context of a limited donor organ supply. SUMMARY: The primary goal of heart transplantation is to improve survival and maximize quality of life. To meet this goal, a careful assessment of patient-specific risks is essential. The optimal approach to patient selection relies on integrating recent prognostication models with a multifactorial assessment of established clinical characteristics, comorbidities and psychosocial factors.

Heart Transplantation as a Result of Pediatric Inflammatory Multisystem Syndrome in an Adolescent.

Several reviews have shown that COVID-19 in children is a relatively mild disease. However, a rare complication affecting children and adolescents after COVID-19 has been identified. Pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), which in some cases manifests itself as a hyperinflammatory syndrome with a multiorgan failure, may lead to death. We report a case of a 17-year-old patient who was admitted to the hospital with cardiogenic shock of unknown etiology. The disease was life-threatening, thus necessitating mechanical ventilation, circulatory support, and extracorporeal therapy due to renal and liver dysfunction. The patient tested negative for SARS-CoV-2 Reverse Transcription Polymerase Chain Reaction. Other infectious causes of illness were excluded. However, the patient had a positive IgG antibody test result and high levels of interleukin-6, which helped to diagnose PIMS-TS. Intravenous immunoglobulin and steroid therapies were initiated, unfortunately, with poor outcome. The patient's critical condition, particularly end-stage heart failure, led to mechanical circulatory support implantation and finally orthotopic heart transplantation. After the surgery, the patient's condition improved gradually. PIMS-TS manifests itself with different clinical images and as a state of varying severity, ultimately causing multiorgan dysfunction with shock resembling toxic shock syndrome. Ultimately, myocardial complications of PIMS-TS necessitated heart transplantation in the described patient.

A Case of Heart Transplantation for Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccination.

Vaccines have become the mainstay of management against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) in the absence of effective antiviral therapy. Various adverse effects of COVID-19 vaccination have been reported, including cardiovascular complications such as myocarditis or pericarditis. Herein, we describe clinical records of a 63-year woman with fulminant myocarditis following ChAdOx1 nCoV-19 vaccination that was salvaged by heart transplantation. She complained chest pain, nausea, vomiting, and fever after the second vaccination. After the heart transplantation, the patient died due to necrotizing pneumonia on the 54th day of onset. Fulminant myocarditis is very rare after ChAdOx1 nCoV-19 vaccination but can be fatal.

Patients After Orthotopic Heart Transplantation With COVID-19: Are We Fast Enough With Vaccinations?

BACKGROUND: Patients after orthotopic heart transplantation (HTx) are especially susceptible to infections owing to permanent need for immunosuppression. Vaccinations against COVID-19 have been available since January 2021 and are recommended in organ recipients. AIM: The aim of this study was to analyze COVID-19 susceptibility and mortality in HTx and number of patients with COVID-19 previously vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PATIENTS AND METHODS: We analyzed a whole cohort of 552 patients after HTx who were SARS-CoV-2 positive and remained under surveillance of the transplantation center during March 2020 to September 2021. RESULTS: Among 552 patients after HTx, 10 were COVID-19 survivors prior to transplantation and 103 had SARS CoV-2 infection after transplantation. Mean age of patients with COVID-19 was 55.6 (±14) years, and mean time from transplantation to SARS-CoV-2 infection was 2856 (±2596) days (range, 16-9569 days; interquartile range, 397-4763 days). Among the patients who were COVID-19 positive, 15 were asymptomatic, 10 died, and 51 infections occurred in the era of vaccinations. In the group of patients who were positive for COVID-19 in 2021, 6 received only a single dose of the mRNA vaccine and 3 were vaccinated twice. Among the vaccinated patients with COVID-19, 2 died of severe COVID-19: 1 after a single dose and 1 after 2 standard doses of the vaccine. CONCLUSION: We observed high susceptibility to SARS-CoV-2 infection in the group of patients after HTx. The majority of patients infected in 2021 did not received the vaccine. Vaccination does not fully protect against severe COVID-19 in patients after HTx.

Successful treatment of disseminated Verruconis gallopava infection in a heart transplant recipient: A case report.

PURPOSE: To describe a case of disseminated Verruconis gallopava infection in a cardiac transplant recipient that was successfully treated with oral posaconazole and intravenous anidulafungin. SUMMARY: A 51-year-old male initially presented with pulmonary manifestations, but subsequently developed cutaneous lesions, fungemia, osteomyelitis of the hip requiring excision, and eventually brain abscesses over the course of 3 months. The patient was successfully treated with various antifungal agents throughout his treatment course and was eventually discharged on oral posaconazole and intravenous anidulafungin. He remained on oral posaconazole suppressive therapy and had had no recurrence of fungal infection after 31 months of follow-up. CONCLUSION: On the basis of this case report, intravenous anidulafungin and chronic suppressive therapy with oral posaconazole can successfully treat disseminated V. gallopava infections.

Characteristics and Outcomes of Heart Transplant Recipients With Coronavirus-19 Disease in a High-volume Transplant Center.

BACKGROUND: Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center. METHODS: We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021. RESULTS: Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible. CONCLUSIONS: Major findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.