Importance of Transplant Era on Post-Heart Transplant Predictive Models: A UNOS Cohort Analysis.

BACKGROUND: The application of posttransplant predictive models is limited by their poor statistical performance. Neglecting the dynamic evolution of demographics and medical practice over time may be a key issue. OBJECTIVES: Our objective was to develop and validate era-specific predictive models to assess whether these models could improve risk stratification compared to non-era-specific models. METHODS: We analyzed the United Network for Organ Sharing (UNOS) database including first noncombined heart transplantations (2001-2018, divided into four transplant eras: 2001-2005, 2006-2010, 2011-2015, 2016-2018). The endpoint was death or retransplantation during the 1st-year posttransplant. We analyzed the dynamic evolution of major predictive variables over time and developed era-specific models using logistic regression. We then performed a multiparametric evaluation of the statistical performance of era-specific models and compared them to non-era-specific models in 1000 bootstrap samples (derivation set, 2/3; test set, 1/3). RESULTS: A total of 34 738 patients were included, 3670 patients (10.5%) met the composite endpoint. We found a significant impact of transplant era on baseline characteristics of donors and recipients, medical practice, and posttransplant predictive models, including significant interaction between transplant year and major predictive variables (total serum bilirubin, recipient age, recipient diabetes, previous cardiac surgery). Although the discrimination of all models remained low, era-specific models significantly outperformed the statistical performance of non-era-specific models in most samples, particularly concerning discrimination and calibration. CONCLUSIONS: Era-specific models achieved better statistical performance than non-era-specific models. A regular update of predictive models may be considered if they were to be applied for clinical decision-making and allograft allocation.

Management of infectious disease syndromes in thoracic organ transplants and mechanical circulatory device recipients: a Delphi panel.

PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.

Association of Arterial Carbon Dioxide Tension Following In-Hospital Cardiac Arrest With Survival and Favorable Neurologic Outcome.

BACKGROUND: In-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. The objective of this study was to study the association of arterial carbon dioxide tension (PaCO2) on survival to discharge and favorable neurologic outcomes in adults with IHCA. METHODS: The study population included 353 adults who underwent resuscitation from 2011 to 2019 for IHCA at an academic tertiary care medical center with arterial blood gas testing done within 24 hours of arrest. Outcomes of interest included survival to discharge and favorable neurologic outcome, defined as Glasgow outcome score of 4-5. RESULTS: Of the 353 patients studied, PaCO2 classification included: hypocapnia (PaCO2 <35 mm Hg, n = 89), normocapnia (PaCO2 35-45 mm Hg, n = 151), and hypercapnia (PaCO2 >45 mm Hg, n = 113). Hypercapnic patients were further divided into mild (45 mm Hg < PaCO2 ≤55 mm Hg, n = 62) and moderate/severe hypercapnia (PaCO2 > 55 mm Hg, n = 51). Patients with normocapnia had the highest rates of survival to hospital discharge (52.3% vs. 32.6% vs. 30.1%, P < 0.001) and favorable neurologic outcome (35.8% vs. 25.8% vs. 17.9%, P = 0.005) compared those with hypocapnia and hypercapnia respectively. In multivariable analysis, compared to normocapnia, hypocapnia [odds ratio (OR), 2.06; 95% confidence interval (CI), 1.15-3.70] and hypercapnia (OR, 2.67; 95% CI, 1.53-4.66) were both found to be independently associated with higher rates of in-hospital mortality. Compared to normocapnia, while mild hypercapnia (OR, 2.53; 95% CI, 1.29-4.97) and moderate/severe hypercapnia (OR, 2.86; 95% CI, 1.35-6.06) were both independently associated with higher in-hospital mortality compared to normocapnia, moderate/severe hypercapnia was also independently associated with lower rates of favorable neurologic outcome (OR, 0.28; 95% CI, 0.11-0.73), while mild hypercapnia was not. CONCLUSIONS: In this prospective registry of adults with IHCA, hypercapnia noted within 24 hours after arrest was independently associated with lower rates of survival to discharge and favorable neurologic outcome.

Sixth monovalent XBB.1.5 vaccine elicits robust immune response against emerging SARS-CoV-2 variants in heart transplant recipients.

Continued circulation of severe acute respiratory syndrome coronavirus 2 has driven the selection of variants with improved ability to escape preexisting vaccine-induced responses, posing a persistent threat to heart transplant recipients (HTRs). The immunogenicity and safety of the updated XBB.1.5-containing monovalent vaccines are unknown. We prospectively enrolled 52 HTRs who had previously received a 5-dose ancestral-derived monovalent and bivalent messenger RNA (mRNA) vaccination schedule to receive the monovalent XBB.1.5 vaccine. Immunogenicity was evaluated using live virus microneutralization assays. The XBB.1.5 monovalent vaccine elicited potent and diverse neutralizing responses and broadened the reactivity spectrum to encompass newer strains, with the highest increase in neutralization activity being more pronounced against XBB.1.5 (15.8-fold) and JN.1 (13.3-fold) than against BA.5 (6.7-fold) and wild-type (4-fold). Notably, XBB.1.5 and JN.1 were resistant to neutralization by prevaccination sera. There were no safety concerns. Our findings support the updating of coronavirus disease 2019 vaccines to match antigenically divergent variants and exclude ancestral spike-antigen to protect HTRs.

Ten-year follow-up cohort of the everolimus versus azathioprine multinational prospective study focusing on intravascular ultrasound findings.

BACKGROUND: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated. METHODS: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year. RESULTS: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002). CONCLUSIONS: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.