Substance Use-Associated Mortality among Heart Donors after the COVID-19 National Emergency Increased but Did Not Affect Peri-Transplant Outcomes.

INTRODUCTION: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. METHODS: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. RESULTS: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). CONCLUSION: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

Heart transplant in a Sars-CoV-2 positive recipient: Management protocol of the world's first case.

The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in China at the end of 2019 has developed into a global outbreak, and COVID- 19 is an ongoing major public health issue. During the pandemic, transplant programs had to devise strategies to deal with the possibility of COVID-19-positive donors and recipients. We describe the case of a heart transplant recipient who tested positive with the SARS- CoV2 swab upon admission to our Unit of Cardiac Surgery when a suitable donor became available. Given his clinical status of end-stage heart failure and the absence of imaging and clinical signs suggestive of COVID-19, and his having been vaccinated with three doses, we decided to proceed with the transplant.

Analysis of clinical cases of new coronavirus infection in patients with a history of heart transplantation

There is a description of two clinical cases of a new coronavirus infection COVID-19 in patients with a history of heart transplantation. Patients who receive immunosuppressants for life are at risk of developing infectious diseases. This requires the vigilance of doctors, especially in the face of a pandemic of a new coronavirus infection. Adequate and timely started therapy increases the effectiveness of treatment and reduces the risk of complications. The complex participation of different specialists is necessary to determine the tactics of treatment, correct pathogenetic and suppressive therapy.Copyright © 2021 Sovero Press Publishing House. All rights reserved.

Effect of the UNOS policy change on rates of rejection, infection and hospital readmission following heart transplantation.

BACKGROUND: The 2018 adult heart allocation policy sought to improve waitlist risk stratification, reduce waitlist mortality and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Post-transplant complications are significantly higher in patients on tMCS before transplantation, and early post-transplant complications impact long-term mortality. We sought to determine if policy change affected early post-transplant complication rates of rejection, infection and hospitalization. METHODS: We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between 11/1/2016 to 10/31/2017 and post-policy (POST) between 11/1/2018 to 10/31/2019. We used a multivariable logistic regression analysis to assess the effect of policy change on post-transplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis. RESULTS: The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p=0.8), hospitalization (p=0.69), and hospitalization due to rejection (p=0.76) and infection (p=0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p=0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras. CONCLUSION: The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early post-transplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term post-transplant mortality.

OPTN/SRTR 2021 Annual Data Report: Heart.

The past 5 years have posed challenges to the field of heart transplantation. The 2018 heart allocation policy revision was accompanied by anticipated practice adjustments and increased use of short-term circulatory support, changes that may ultimately serve to advance the field. The COVID-19 pandemic also had an impact on heart transplantation. While the number of heart transplants in the United States continued to increase, the number of new candidates decreased slightly during the pandemic. There were slightly more deaths following removal from the waiting list for reasons other than transplant during 2020, and a decline in transplants among candidates listed as status 1, 2, or 3 compared with the other statuses. Heart transplant rates decreased among pediatric candidates, most notably among those younger than 1 year. Despite this, pretransplant mortality has declined for both pediatric and adult candidates, particularly candidates younger than 1 year. Transplant rates have increased in adults. The prevalence of ventricular assist device use has increased among pediatric heart transplant recipients, while the prevalence of short-term mechanical circulatory support, particularly intra-aortic balloon pump and extracorporeal membrane oxygenation, has increased among adult recipients.

The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.

Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.

Severity of SARS-CoV-2 Omicron variant infection in heart transplant recipients.

SARS-CoV-2 Omicron variant was first detected in France mid-November 2021 in wastewater treatment plants while cases started to increase at the beginning of December. The maximum incidence occurred in mid-January 2022. The Omicron wave spread rapidly throughout France in general population with lower case-fatality rate compared with previous waves. Little is known about infection with Omicron variant in heart transplant (HT) recipients. In this study, we examined incidence and mortality rate of COVID-19 in the general population and among 1,263 HT recipients during the period from June, 2021 to February, 2022, described characteristics of HT recipients infected with SARS-CoV-2 during Omicron (December 1st, 2021-February 7, 2022) and Delta (June 1st- November 30, 2021) periods, and compared hospital course of HT recipients with Omicron and Delta variant infection. Our findings contrast with the reported lower severity for Omicron variant infection compared with Delta variant infection in immunocompetent individuals.

Elevated Levels of Neutrophil-to Monocyte Ratio Are Associated with the Initiation of Paroxysmal Documented Atrial Fibrillation in the First Two Months after Heart Transplantation: A Uni-Institutional Retrospective Study.

BACKGROUND: Heart transplantation represents the treatment for patients with end-stage heart failure (HF) being symptomatic despite optimal medical therapy. We investigated the role of NMR (neutrophil-to-monocyte ratio), NLR (neutrophil-to-lymphocyte ratio), NPR (neutrophil-to-platelet ratio), NWR (neutrophil-to-white cells ratio), MLR (monocyte-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), MWR (neutrophil-to-white cells ratio), and LWR (lymphocyte-to-white cells ratio) at the same cut-off values previously studied, to predict complications after heart transplant within 2 months after surgery. METHODS: From May 2014 to January 2021, was included 38 patients in our study from the Cardiovascular and Transplant Emergency Institute of Târgu Mureș. RESULTS: Preoperative NMR > 8.9 (OR: 70.71, 95% CI: 3.39-1473.64; p = 0.006) was a risk factor for the apparition of post-operative paroxysmal atrial fibrillation (Afib). In contrast, preoperative MWR > 0.09 (OR: 0.04, 95% CI: 0.003-0.58; p = 0.0182) represented a protective factor against AFib, but being the risk of complications of any cause (OR: 14.74, 95% CI: 1.05-206.59, p = 0.0458). CONCLUSION: Preoperative elevated levels of NMR were associated with the apparition of documented AFib, with high levels of MWR as a protective factor. High MWR was a risk factor in developing complications of any cause in the first 2 months after heart transplantation.

Rapid triage and transition to telehealth for heart transplant patients in the COVID-19 pandemic setting.

BACKGROUND: In the setting of the COVID-19 pandemic, a rapid uptake of telehealth services was instituted with the aim of reducing the spread of disease to vulnerable patient populations including heart transplant recipients. METHODS: Single-center, cohort study of all heart transplant patients seen by our institution's transplant program during the first 6 weeks of transition from in-person consultation to telehealth (23 March - 5 June 2020). RESULTS: Face-to-face consultation allocation strongly favored patients in the early post-operative period (34 vs. 242 weeks post-transplant; p < 0.001). Telehealth consultation dramatically reduced patient travel and wait times (80 min per visit saved in telehealth patients). No apparent excess re-hospitalization or mortality was seen in telehealth patients. CONCLUSIONS: With appropriate triage, telehealth was feasible in heart transplant recipients, with videoconferencing being the preferred modality. Patients seen face-to-face were those triaged to be higher acuity based on time since transplant and overall clinical status. These patients have the expected higher rates of hospital re-admission, and therefore should continue to be seen in person.

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.

Use of REGEN-COV in children after heart transplantation for treatment and post-exposure prophylaxis of COVID-19.

COVID-19 pandemic continues to evolve and new variants like Delta and Omicron have been discovered. REGEN-COV is a recombinant human monoclonal antibody to the spike protein of SARS-CoV-2 which received emergency use authorisation for treatment and post-exposure prophylaxis in patients with high risk of progression to severe disease. We review our experience with use of REGEN-COV in paediatric heart transplant patients.

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.

Risks of paxlovid in a heart transplant recipient.

The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.

Atrial Flutter in Particular Patient Populations.

"Despite being one of the best understood cardiac arrhythmias, the clinical meaning of atrial flutter varies according to the specific context, and its optimal treatment may be limited by both the suboptimal response to rate/rhythm control drugs and by the complexity of the underlying substrate. In this article, we present a state-of-the-art overview of mechanisms, prognostic impact, and medical/interventional management options for atrial flutter in several specific patient populations, including heart failure, cardiomyopathies, muscular dystrophies, posttransplant patients, patients with respiratory disorders, athletes, and subjects with preexcitation, aiming to stimulate further research in this challenging field and facilitate appropriate patient care."

Veno-venous ECLS rescue for a heart transplant recipient with COVID-19, a case report.

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).

Patterns and outcomes of COVID-19 donor utilization for heart transplant.

BACKGROUND: The outcomes following COVID-19 positive donor (CPD) utilization for heart transplant are unknown. METHODS: UNOS database was analyzed for heart transplants performed from the declaration of COVID-19 pandemic until September 30, 2022. RESULT: Since the onset of pandemic, there were 9876 heart transplants reported. COVID-19 antigen or NAT results were available in 7698 adult donors within 14 days of donation, of which 177 (2.3%) were positive. There was no difference in recipient demographics, including age (COVID positive donor vs. negative: 55 vs. 56 years, p = .2) and BMI. Listing status 1 and 2 were similar in both groups (7% vs. 10% and 48% vs. 49% respectively, p = .4). Durable and temporary mechanical support were similar in both groups pre-transplant (both groups 33%, p = .9). There was no difference in days on the waitlist (median 31 days, p = .9). Simultaneous renal transplant rates were similar (11% vs. 10%, p = .9). CPD utilization has increased since the onset of the pandemic, and the adoption is present across most UNOS regions. Post-transplant, there was no difference in length of stay (median 16 vs. 17 days, p = .9) and acute rejection episodes prior to discharge (3% vs. 8%, p = .1). In survival analysis of 90-day follow up, number of deaths reported were comparable (5% in both groups, p = .9) Follow-up LVEF was comparable (62% vs. 60%, p = .4). CONCLUSION: Active COVID-19 infection in donors did not affect survival or rejection rates in the short-term post-heart transplant.

Low acceptance rate of COVID-19 vaccination and reduced quality of life among heart transplant recipients during the COVID-19 pandemic.

OBJECTIVES: To investigate the impact of the current coronavirus disease 2019 (COVID-19) pandemic on the quality of life (QoL) and status of COVID-19 vaccination in heart transplant recipients (HTRs). METHODS: Patients who underwent allogeneic heart transplants between June 2006 and December 2019, who survived were selected from a follow-up registration form at our center. Data were collected using questionnaires in 2021, the QoL survey was conducted using the MOS 36-item Short-Form Health Survey (SF-36) and compared to the same time frame in 2019. The patients were divided into two groups: post-epidemic (A) and pre-epidemic (B) groups. We also recorded whether the participants had been vaccinated against COVID-19 (Beijing Sinovac COVID-19 vaccine). All the data obtained were analyzed. RESULTS: There were 88 patients who participated in the study. Only 12 (13.6%) were vaccinated. In terms of SF-36 scale assessments, after the outbreak of the COVID-19 pandemic, Group A scored lower in vitality [52.5(49.0, 58.0) vs. 75.0(69.0, 79.0), p < .001], social functioning [54.0(50.5, 58.0) vs. 74.0(67.5, 78.0), p < .001], role emotional [58.5(55.0, 62.0) vs. 67.0(63.0, 71.0), p < .001], and mental health [58.5(55.0, 62.0) vs. 76.0(72.0, 79.0), p < .001]. In Group A the mental component summary (MCS) significantly decreased [222.0(214.5, 230.0) vs. 289.0(277.5, 299.5), p < .001]. The PCS and MCS of HTRs who had been vaccinated against COVID-19 were significantly higher than those who had not [PCS: 283.5(280.0, 287.0) vs. 276.0(271.0, 279.0), p < .001; MCS: 245.0(141.5, 254.0) vs. 220.0(213.5, 226.5), p < .001]. CONCLUSION: Low acceptance levels of COVID-19 vaccination were observed in the HTRs. The QoL of the HTRs decreased after the COVID-19 pandemic.

Humoral and cellular immune response after severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccination in heart transplant recipients: An observational study in France.

Introduction: Heart transplant (HT) recipients have a high risk of developing severe COVID-19. Immunoglobulin G antibodies are considered to provide protective immunity and T-cell activity is thought to confer protection from severe disease. However, data on T-cell response to mRNA vaccination in a context of HT remains limited. Methods: In 96 HT patients, a IFN-γ release assay and an anti-Spike antibody test were used to evaluate the ability of SARS-CoV-2 mRNA vaccines to generate cellular and humoral immune response. Blood samples were collected few weeks to 7 months after vaccination. Multiple fractional polynomial and LASSO regression models were used to define predictors of T-cell response. Results: Three to five months after vaccination, three doses of vaccine induced a positive SARS-CoV-2 T-cell response in 47% of recipients and a positive humoral response in 83% of recipients, 11.1% of patients remained negative for both T and B cell responses. Three doses were necessary to reach high IgG response levels (>590 BAU/mL), which were obtained in a third of patients. Immunity was greatly amplified in the group who had three vaccine doses plus COVID-19 infection. Conclusion: Our study revealed that T and B immunity decreases over time, leading us to suggest the interest of a booster vaccination at 5 months after the third dose. Moreover, a close follow-up of immune response following vaccination is needed to ensure ongoing immune protection. We also found that significant predictors of higher cellular response were infection and active smoking, regardless of immunosuppressive treatment with mycophenolate mofetil (MMF).