Lung Transplantation Guidelines Research Articles

INTERNATIONAL SOCIETY FOR HEART AND LUNG TRANSPLANTATION GUIDELINES FOR THE EVALUATION AND CARE OF CARDIAC TRANSPLANT CANDIDATES-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review.

Lung transplantation (LUTX) is often complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping. Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following International Society for Heart and Lung Transplantation (ISHLT) guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases. Among the 1050 papers screened, 25 prospective observational studies were included, with only nine conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44-119)). Most (n=21) compared PGD grade 3 to less severe PGD, but only four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve analysis, yielding a median value of 0.58 (0.51-0.78) in 406 patients (276 double LUTX). Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms and advanced statistical approaches are essential.

Temporarily Reversing Warfarin With Low-Dose 4-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Patients Undergoing an Invasive Procedure.

American Association for Thoracic Surgery and The International Society for Heart and Lung Transplantation (AATS/ISHLT) guidelines recommend warfarin in patients with continuous-flow left ventricular assist devices (LVADs) to reduce the risk of device thrombosis and systemic embolization. Left ventricular assist device patients often undergo elective and emergent procedures that require interrupted anticoagulation. Data and experience vary on the optimal strategy to rapidly reverse warfarin in LVAD patients when an emergent procedure is planned. The purpose of this study was to describe the use of 4-factor prothrombin complex concentrate (PCC4) for warfarin reversal in patients with LVADs undergoing elective and emergent procedures. This retrospective, single-center, cohort review describes the use of PCC4 in patients with LVADs who require warfarin reversal for elective or emergent procedures. The primary outcome was a composite incidence of pump thrombosis, venous thromboembolism, and ischemic stroke within 30 days of PCC4 administration. In total, 14 patients received 17 administrations of PCC4. One patient received 3 administrations, and 1 other patient received 2 administrations during separate encounters. The median dose was 500 units or 6.6 units/kg (range = 4.2-14.1 units/kg). Of the PCC4 administrations, 82% (14/17) were for low bleed risk procedures and 76% (13/17) were for elective procedures. There were no cases of pump thrombosis, venous thromboembolism, or stroke within 30 days of the procedure. Low-dose PCC4 appears to be a safe and effective temporary reversal strategy for patients with LVADs undergoing low-bleed risk elective procedures.

Temporary Mechanical Circulatory Support During Bariatric Surgery: A Novel Bridge to Durable Left Ventricular Assist Device and Cardiac Transplantation.

Advanced heart failure (HF) with comorbid severe obesity presents a unique surgical dilemma: bariatric surgery may help patients meet cardiac transplantation body mass index (BMI) criteria, but poor cardiac function puts them at increased intraoperative risk. Per International Society for Heart and Lung Transplantation (ISHLT) guidelines BMI > 35 is a contraindication for orthotopic heart transplantation. Temporary mechanical circulatory support (MCS) with Impella 5.5 during bariatric surgery, as presented in this report, may help solve this dilemma for some patients. We present three patients with severe obesity and advanced heart failure (HF) who underwent successful bariatric surgery while supported by Impella 5.5 (Abiomed, Inc., Danvers, MA).

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux.

Gastroesophageal reflux is associated with poorer outcomes after lung transplant, likely through recurrent aspiration and allograft injury. Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes, the role of esophageal manometry in the assessment of lung transplant patients remains debated, and the impact of esophageal dysmotility on transplant outcomes is unclear. Of particular interest is ineffective esophageal motility (IEM) and its associated impact on esophageal clearance. To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018. Patients with pre-transplant anti-reflux surgery were excluded. Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing. Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection, defined histologically per International Society of Heart and Lung Transplantation guidelines. Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery, last clinic visit, or death. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between groups. Of 184 subjects (54% men, mean age: 58, follow-up: 443 person-years) met criteria for inclusion. Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis (41%). During the follow-up period, 60 subjects (33.5%) developed acute rejection. The all-cause mortality was 16.3%. Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection [hazard ratio (HR): 1.984, 95%CI: 1.03-3.30, P = 0.04], confirmed on Kaplan-Meier curve. On multivariable analysis, IEM remained independently associated with acute rejection, even after controlling for potential confounders such as the presence of acid and nonacid reflux (HR: 2.20, 95%CI: 1.18-4.11, P = 0.01). Nonacid reflux was also independently associated with acute rejection on both univariate (HR: 2.16, 95%CI: 1.26-3.72, P = 0.005) and multivariable analyses (HR: 2.10, 95%CI: 1.21-3.64, P = 0.009), adjusting for the presence of IEM. Pre-transplant IEM was associated with acute rejection after transplantation, even after controlling for acid and nonacid reflux. Esophageal motility testing may be considered in lung transplant to predict outcomes.

Non-invasive detection of cardiac allograft rejection among heart transplant recipients using an electrocardiogram based deep learning model.

Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78-0.90] and 95% (19/20; 95% CI: 75-100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61-0.96) and 100% (2/2; 95% CI: 16-100%) sensitivity. An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

Evaluation of Routine Ear, Nose, and Throat Screening in Heart Transplant Candidates: A Retrospective Cohort Study

Patients with end-stage heart failure refractory to medication can be treated with a heart transplant (HTx). These patients are subjected to a preoperative screening procedure according to International Society for Heart and Lung Transplantation guidelines. Additionally, in our hospital, a routine ear, nose, and throat (ENT) screening is performed, directed toward the identification of asymptomatic infections and head and neck neoplasms. There are no studies demonstrating that this screening has additional value in these patients. To investigate the yield of protocolled ENT screening in candidates for HTx, we retrospectively reviewed the medical records of patients who were subjected to the screening procedure between 2012 and 2020. The study population consisted of 251 patients of whom 177 (70.5%) were male with a median age of 52 years (IQR, 45-59 years). Ten patients (4.0%) were diagnosed with an infection (sinus) or a neoplasm, resulting in a number needed to screen of 25. In all cases, ENT consultation or sinus radiography did not influence the decision to list patients for HTx. Furthermore, no major ENT infections or occurrence of de novo head and neck malignant neoplasm were observed during follow-up after HTx. The clinically relevant yield of protocolled ENT screening in candidates for HTx is low. Based on these findings, we believe that only patients with abnormal findings on a routine sinus computed tomography scan and/or specific ENT complaints should be referred to an otorhinolaryngologist.

The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients

David Baran, Tiffany Buda, Adam Cochrane, Maria Crespo Leiro, Anne Dipchand, Brian Feingold, Kathleen Grady, Edward Horn, Maryl Johnson, Donna Mancini, Sean Pinney, Heather Ross, Kari Wujcik, Andreas Zuckermann

Screening for cardiac allograft rejection among heart transplant recipients using an electrocardiogram-based deep learning model

Abstract Background Current approaches utilizing non-invasive methods to screen for cardiac allograft rejection (gene expression profiling and cell free DNA) have yet to be broadly integrated into heart transplant management and have shown limited discrimination (AUCs of 0.68 and 0.77, respectively). Changes in the electrocardiogram (ECG) have been reported at the time of severe cardiac rejection, including low voltages and conduction abnormalities. It remains unknown if subtle ECG changes correlating with cardiac allograft rejection can be detected earlier using machine learning methods. Purpose We sought to develop an artificial intelligence (AI) model to detect cardiac allograft rejection based on the 12 lead ECG. Methods We identified all patients who underwent a heart transplant at 3 hospital sites within a single health system from Jan 1998 through Apr 2021 and extracted digital 12-lead ECG data as well as endomyocardial biopsy pathology results from the electronic medical record. We partitioned our data into a training (80%), validation (10%), and test set (10%) based on a group stratification sampling. Each patient was present in only one set and each set had a positivity rate of 2.6% with 6,074/758/758 ECGs belonging to 1,146/140/141 unique patients in each set respectively. Cardiac allograft rejection was defined as moderate or severe acute cellular rejection based on International Society for Heart and Lung Transplantation (ISHLT) guidelines. A convolutional neural network, using the 12-lead ECG data as input, was trained with hyperparameter optimization for regularization, learning rate adjustments, and class weights. Model performance metrics were based on the test data and estimated using the final model architecture. Results 1,587 heart transplant recipients who had at least one endomyocardial biopsy were evaluated for inclusion. We limited our sample to ECGs performed within 30 days of the biopsy date (7,590 ECGs, representing 1,425 unique patients). Our study population had a median age of 55.8 years and 28.7% were female. The median number of ECG-biopsy pairs per patient was 5. The majority of endomyocardial biopsy results were classified as none or mild rejection (97.1%), and 2.9% had moderate/severe rejection. The ECG-based AI model detected cardiac allograft rejection with an area under the receiver operative curve (AUC) of 0.84 in the test set. The sensitivity, specificity, positive and negative predictive values were 95%, 52.6%. 5.2% and 99.7% respectively. Conclusions An AI-ECG model appears to outperform novel non-invasive laboratory tests (gene expression profiling and cell free DNA) for detecting cardiac allograft rejection and does not require a blood draw or the additional complexities surrounding sample processing. This model relies on a readily available and relatively inexpensive test, the ECG. In addition, AI predictions can be made available within a few minutes following ECG acquisition. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic

Finding the Road to Rome in Cardiac Allograft Vasculopathy Imaging Surveillance.

Finding the Road to Rome in Cardiac Allograft Vasculopathy Imaging Surveillance.

Incidence of acute rejection and patient survival in combined heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is indicated for patients with concomitant end-stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor-specific antibodies (DSAs) compared with heart-alone transplantation (HA). We conducted a retrospective analysis of 32 CHLT and 280 HA recipients in a single-center experience. The primary outcome was incidence of ACR based on protocol and for-cause myocardial biopsy. Rejection was graded by the International Society of Heart and Lung Transplantation guidelines with Grade 2R and higher considered significant. Secondary outcomes included the development of new DSAs, cardiac function, and patient and cardiac graft survival rates. Of CHLT patients, 9.7% had ACR compared with 45.3% of HA patients (p<0.01). Mean pretransplant calculated panel reactive antibody (cPRA) levels were similar between groups (CHLT 9.4% vs. HA 9.5%; p=0.97). Among patients who underwent testing, 26.9% of the CHLT and 16.7% of HA developed DSA (p=0.19). Despite the difference in ACR, patient and cardiac graft survival rates were similar at 5years (CHLT 82.1% vs. HA 80.9% [p=0.73]; CHLT 82.1% vs. HA 80.9% [p=0.73]). CHLT reduced the incidence of ACR in the cardiac allograft, suggesting that the liver offers immunoprotection against cellular mechanisms of rejection without significant impacts on patient and cardiac graft survival rates. CHLT did not reduce the incidence of de novo DSA, possibly portending similar long-term survival among cardiac allografts in CHLT and HA.

Predicting Left Ventricular Assist Device Outcomes Utilizing the Stanford Integrated Psychosocial Assessment for Transplant Measure

Objective: Durable mechanical circulatory support is a proven therapy to extend survival for patients with end-stage heart failure (HF). The International Society for Heart and Lung Transplantation guidelines recommend a detailed psychosocial assessment when selecting candidates for durable mechanical circulatory support. Currently, there are no formally validated psychosocial evaluation tools for left ventricular assist device (LVAD) candidacy. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) uses a multidisciplinary algorithm to evaluate the impact of pre-transplant risk factors on post-transplant outcomes. Emerging literature suggests that the SIPAT might be useful for assessing psychosocial risk factors for LVAD outcomes. Methods: A total of 268 consecutive patients (median age 66 years, 84.6% male) with terminal HF were evaluated before LVAD implantation with a SIPAT assessment. Key outcomes included readmission and mortality rates at 30 days and two years. Results: After screening, 234 subjects met the inclusion criteria and were analyzed. The Patient Readiness subscale of the SIPAT was statistically significant in predicting two-year mortality (B = .167, P &lt; .001; Nagelkerke r2 = .106). Scores on the SIPAT did not correlate to 30-day readmission, 30-day mortality, or two-year readmission rates. Discussion: In this study, only the Patient Readiness score was associated with mortality at two-years post-implantation. This research elucidates the potential longer-term impact of psychosocial factors on LVAD outcomes and the SIPAT’s utility in evaluating LVAD candidacy.

Analysis of sex-based differences in clinical and molecular responses to ischemia reperfusion after lung transplantation

BackgroundSex and hormones influence immune responses to ischemia reperfusion (IR) and could, therefore, cause sex-related differences in lung transplantation (LTx) outcomes. We compared men’s and women’s clinical and molecular responses to post-LTx IR.MethodsIn 203 LTx patients, we used the 2016 International Society for Heart and Lung Transplantation guidelines to score primary graft dysfunction (PGD). In a subgroup of 40 patients with blood samples collected before LTx (T0) and 6, 24, 48 (T48), and 72 h (T72) after lung reperfusion, molecular response to IR was examined through serial analysis of circulating cytokine expression.ResultsAfter adjustment, women had less grade 3 PGD than men at T48, but not at T72. PGD grade decreased from T0 to T72 more often in women than men. The evolution of PGD (the difference in mean PGD between T72 and T0) was greater in men. However, the evolution of IL-2, IL-7, IL-17a, and basic fibroblast growth factor levels was more often sustained throughout the 72 h in women. In the full cohort, we noted no sex differences in secondary clinical outcomes, but women had significantly lower peak lactate levels than men across the 72 h.ConclusionsMen and women differ in the evolution of PGD and cytokine secretion after LTx: Women have a more sustained proinflammatory response than men despite a greater reduction in PGD over time. This interaction between cytokine and PGD responses warrants investigation. Additionally, there may be important sex-related differences that could be used to tailor treatment during or after transplantation.

Association between continuous-flow left ventricular assist device infections requiring long-term antibiotic use and post-heart transplant morbidity and mortality.

There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD. This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively. We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups. LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant.

MILD PULMONARY HYPERTENSION IN ADVANCED HEART FAILURE PATIENTS IS ASSOCIATED WITH BOTH ABNORMAL RESISTIVE AND PULSATILE LOAD AND LOWER 3-YEAR SURVIVAL

<h3>BACKGROUND</h3> Current guidelines require patients with heart failure (HF) being evaluated for advanced therapies such as heart transplantation or left ventricular assist device (LVAD) implantation to undergo right heart catheterization to identify the presence of pulmonary hypertension (PH). PH that is irreversible is a relative contraindication to heart transplantation and associated with poor prognosis. Based on the International Society for Heart and Lung Transplantation guidelines, reversibility is assessed with a vasodilator challenge if pulmonary artery systolic pressure (PASP) is > 50 mmHg, and either transpulmonary gradient (TPG) is > 15 mmHg or pulmonary vascular resistance (PVR) is > 3 WU. However, the most updated 6th World Symposium on Pulmonary Hypertension defined PH more broadly as to mean pulmonary artery pressure (mPAP) > 20 mmHg. As such, there is an intermediate group of patients with mild PH not meeting the threshold to receive a vasodilator challenge to determine whether mild PH is reversible. Our aim was to assess the hemodynamic characteristics of this group and determine whether they are at risk of worse clinical outcomes. <h3>METHODS AND RESULTS</h3> A retrospective analysis was performed of 175 patients with heart failure who were referred to our centre for right heart catheterization as part of evaluation for candidacy for advanced heart failure therapies. Patients were divided into three groups based on initial hemodynamics: patients with mPAP < 20 mmHg (No-PH, n=57), patients with significant PH meeting current guideline criteria for a vasodilator challenge (PH+V, n=41) and patients with mPAP > 20 mmHg that did not meet the threshold for vasodilator challenge (PH-V, n=77). Compared to the No-PH group, the PH-V group did not have a significantly different stroke volume index or cardiac index, however, they had a significantly higher PVR, indicating greater resistive load, and lower pulmonary artery compliance (PAC), indicating higher pulsatile load (Table). The PH-V group also had significantly higher mean right atrial pressure (mRAP) compared to the No-PH group, suggesting right ventricular decompensation. Composite pre-and post-intervention three-year survival after catheterization appeared lower in both PH+V and PH-V patients compared to the No-PH group (Figure). <h3>CONCLUSION</h3> HF patients assessed for advanced therapies identified as having mild PH have increased pulmonary pulsatile and resistive load, along with elevated right-sided filling pressures, and have increased mortality. Currently, this group does not undergo vasodilator testing to determine PH reversibility. Whether mild PH is modifiable, and its relationship to outcomes after heart transplantation or LVAD implant requires further study.

The Impact of Narrowing Perioperative Antibiotic Prophylaxis for Left-Ventricular-Assist Device Implantation

Background: Left-ventricular-assist device (LVAD)–related infections occur in 20%–40% of LVAD recipients and may result in up to 10% of LVAD-related deaths. Optimal surgical infection prophylaxis for LVAD implantation is not well defined. Our institution historically used a 4-drug surgical infection prophylaxis regimen of fluconazole, ciprofloxacin, rifampin, and vancomycin as recommended by the device manufacturer. In January 2020, a 2-drug surgical infection prophylaxis regimen of vancomycin and cefazolin was implemented to reduce broad-spectrum antibiotic use while preserving gram-positive coverage. The primary objective of this study was to compare LVAD-associated infection rates before and after changing surgical infection prophylaxis. Methods: A retrospective review of patients who underwent LVAD implantation between January 2018 and January 1, 2021, was performed. Definitions of LVAD-associated infections and non-LVAD infections were based on the International Society for Heart and Lung Transplantation guidelines. Infection rates at 2 weeks and 30 days after implantation and 30-day mortality were compared between the 4-drug surgical infection prophylaxis regimen (January 2018–December 2019) and the 2-drug regimen (January 2020–January 2021). Additional data collected included demographics, cause of cardiomyopathy, type of infection, and causative organism. Results: In total, 51 patients were in the 4-drug surgical infection prophylaxis group and 23 patients were in the 2-drug surgical infection prophylaxis group. Baseline characteristics between the groups were similar. The cause of cardiomyopathy in both groups was predominantly nonischemic (67% vs 70%, = .81), and most patients received a Heartmate III device (84% vs 100%, P = .06). There was no statistical difference between infection rates in the 4-drug and 2-drug prophylaxis groups at 2 weeks or 30 days (Table 1). The 30-day mortality rate was 4% in the 4-drug group versus 13% in the 2-drug group (P = .17). No deaths were due to infections. Gram-negative and fungal LVAD–associated infections were rare: 4% versus 4% (P = .99) for gram-negative infections and 2% versus 0% (P = .99) for fungal infections. The most commonly isolated organisms were Staphylococcus aureus and coagulase-negative Staphylococcus in both groups. Pneumonia was the most common infection in both groups (Figure 1). Conclusions: We did not observe a significant increase in infection or mortality with narrowing of perioperative antibiotics. However, these results should be interpreted cautiously given the small sample size. Larger studies are needed to confirm these findings.Funding: NoDisclosures: None

Incidence of primary graft dysfunction is higher according to the new ISHLT 2016 guidelines and correlates with clinical and molecular risk factors.

BackgroundPrimary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients.MethodsIn this retrospective study, we extracted data from the medical records of 127 patients who underwent lung transplantation between 1/1/2016–12/31/2018. PGD was defined as PGD3 present at 48 and/or 72 hours post-reperfusion. We used the 2005 and the updated 2016 guidelines to assess clinical risk factors, outcomes, and baseline biomarkers for PGD.ResultsOn the basis of the 2016 and 2005 guidelines, we identified PGD in 37% and 26% of patients, respectively. PGD was significantly associated with extracorporeal life support, large body mass index, and restrictive lung disease using the 2016 but not the 2005 guidelines. Based on the 2016 guidelines, pretransplant levels of several biomarkers were associated with PGD; using the 2005 guidelines, only increased interleukin-2 levels were significantly associated with PGD. No preoperative biomarkers were associated with PGD using either guidelines after adjusting for clinical variables. Postoperative morbidity and 1-year mortality were similar regardless of guidelines used.ConclusionsOur findings suggest that refinements in the PGD scoring system have improved the detection of graft injury and associated risk factors without changing its ability to predict postoperative morbidity and mortality.

The role of cardiopulmonary exercise testing in a contemporary heart failure population

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiopulmonary exercise testing (CPET) is used for risk stratification in patients with chronic heart failure (CHF). However, there is a lack of information regarding CPET prognostic power in patients under new HF therapies such as sacubitril/valsartan, Mitraclip, IV iron or SGLT2 inhibitors. The aim of this study was to evaluate the prognostic value of CPET parameters in a contemporary subset of patients with optimal medical and device therapy for CHF. Methods Retrospective evaluation of patients with CHF submitted to CPET in a tertiary center. Patients were followed up for 24 months for the composite endpoint of cardiac death, urgent heart transplantation or left ventricular assist device. CPET parameters, including peak oxygen consumption (pVO2) and VE/VCO2 slope, were analysed and their predictive power was measured. HF events were stratified according to cut-off values defined by the International Society for Heart and Lung Transplantation (ISHLT) guidelines: pVO2 of ≤12 mL/Kg/min and VE/VCO2 slope of &amp;gt;35. Results CPET was performed in 204 patients, from 2014 to 2018. Mean age was 59 ± 13 years, 83% male, with a mean left ventricular ejection fraction of 33 ± 8%, and a mean Heart Failure Survival Score of 8.6 ± 1.3. The discriminative power of CPET parameters is displayed in the Table. In patients with pVO2 ≤12 mL/Kg/min, the composite endpoint occurred in 18% of patients. A pVO2 value of ≤12 mL/Kg/min had a positive predictive power of 18% while pVO2 &amp;gt;12 had a negative predictive power of 93%. Regarding VE/VCO2 slope &amp;gt;35, the composite endpoint occurred in 13% of patients. A VE/VCO2 slope value of &amp;gt;35 had a positive predictive power of 13% while VE/VCO2 slope &amp;lt;35 had a negative predictive power or 94%. Conclusion Using ISHLT guideline cut-off values for advanced HF therapies patient selection, there was a reduced number of HF events (&amp;lt;20%) at 24 months in patients under optimal CHF therapy. While pVO2 and VE/VCO2 slope are still valuable parameters in risk stratification, redefining cut-off values may be necessary in a modern HF population. Discriminative power of CPET parameters Parameters HR; 95% CI AUC p-value Peak VO2 0.824 (0.728-0.934) 0.781 0.001 Percent of predicted pVO2 0.942 (0.907-0.978) 0.774 0.002 VE/VCO2 slope 1.068 (1.031-1.106) 0.756 0.008 Cardiorespiratory optimal point 1.118 (1.053-1.188) 0.746 0.004 PETCO2 maximum exercise 0.854 (0.768-0.950) 0.775 0.003 Ventilatory Power 0.358 (0.176-0.728) 0.796 0.002 HR Hazard ratio, AUC: Area under the curve, PETCO2: end-tidal CO2 pressure

Understanding the Impact of Hypertension on Left Ventricular Assist Device Pump Function and Thrombotic Risk.

Understanding the Impact of Hypertension on Left Ventricular Assist Device Pump Function and Thrombotic Risk.

Markers of Immune Function in Heart Transplantation: Implications for Immunosuppression and Screening for Rejection.

Recent developments in high-throughput DNA and RNA sequencing technologies have facilitated the development of noninvasive assays to monitor heart transplant rejection. In this review, we summarize existing assays employed for the surveillance of allograft rejection, as well as promising future directions for such tests in the molecular biology field. The AlloMap genome expression profiling assay remains the only noninvasive test for rejection surveillance and is incorporated into the International Society of Heart and Lung Transplantation guidelines. Other efforts have focused on messenger RNA (mRNA), microRNA (miRNA), and donor-derived cell-free DNA (dd-cfDNA) as potential viable biomarkers. Mitochondrial pathways in allograft necroptosis and inflammation signaling may represent a novel direction for future research endeavors. Although endomyocardial biopsy remains the gold standard, several converging areas of molecular biology could soon yield successful alternative methods of heart transplant rejection monitoring, with the distinct advantage of avoiding procedural complications.