Time Of Heart Transplantation Research Articles

Abstract 16120: Efficacy of an Electronic Medical Record Alert System in Identifying Cardiac Implantable Electronic Device Infection

Introduction: Cardiac Implantable Electronic Device infection (CIED-I) is common, morbid, and frequently under recognized. Electronic Medical Record (EMR) based alerts have been proposed as a solution to improve detection of CIED-I. Hypothesis: Development of a real-time EMR algorithm to identify CIED-I can improve recognition of patients with CIED-I. Methods: An EMR (Epic, Verona, WI) alert system to identify inpatients with CIED-I was developed based on the presence of CIED and positive blood cultures. The presence of CIED was determined using patient problem list, structured data elements describing device implantation, and prior device interrogation. Alerts were generated each time a patient with CIED had a positive blood culture. We examined patients admitted between January 2020 - March 2023. Identified patients were adjudicated manually to confirm: (1) the presence of CIED and (2) true bacteremia versus contaminant based on patient and microbiological characteristics. Results: The algorithm generated 255 alerts, corresponding to 100 unique patients over 142 hospitalizations. Of these alerts, 213 appropriately identified 88 unique patients with positive blood cultures and CIEDs, resulting in an alert specificity of 84% and patient specificity of 88%. The remaining 42 (16.6%) alerts occurred in 10 patients who no longer had CIED due to prior CIED extraction (6 at the time of heart transplant and 4 with extraction without reimplantation) as well as 2 patients with erroneous blood culture identification (one positive syphilis antibody test and one lab documentation error). In patients with appropriate alerts, 27 patients had 4/4 positive blood culture bottles, 5 patients had 3/4, 10 patients had 2/4, 41 patients had 1/4, 2 patients had 2/2, and 1 patient had 1/2. The positive predictive value of the algorithm to identify true bacteremia was 0.65 (138/213). Conclusions: The algorithm has high specificity to identify patients with possible CIED infection. Improving the accuracy of device detection, by incorporating radiology imaging or history of extraction, could further improve specificity. Positive predictive value and alert fatigue could be improved by stratifying alerts by blood culture species and total number of positive blood cultures.

Predictors of Survival After Heart Transplant in the New Allocation System: A UNOS Database Analysis.

Clinical predictors of posttransplant graft loss since the United Network for Organ Sharing (UNOS) heart allocation system change have not been well characterized. Single organ adult heart transplants from the UNOS database were identified (n = 10,252) and divided into a test cohort (n = 6,869, 67%) and validation cohort (n = 3,383, 33%). A Cox regression analysis was performed on the test cohort to identify recipient and donor risk factors for posttransplant graft loss. Based on the risk factors, a score (max 16) was developed to classify patients in the validation cohort into risk groups of low (≤1), mid (2-3), high (≥4) risk. Recipient factors of advanced age, Black race, recipient blood group O, diabetes, etiology of heart failure, renal dysfunction, elevated bilirubin, redo-transplantation, elevated pulmonary artery pressure, transplant with a durable ventricular assist device, or transplant on extracorporeal membrane oxygenation (ECMO) or ventilator were associated with more posttransplant graft loss. Donor factors of ischemic time and donor age were also associated with outcomes. One year graft survival for the low-, mid-, high-risk groups was 94%, 91%, and 85%, respectively. In conclusion, easily obtainable clinical characteristics at time of heart transplant can predict posttransplant outcomes in the current era.

Abstract P2060: Gja1-20k Expression Increases With Left Ventricular Mechanical Unloading In Patients With Arrhythmogenic Cardiomyopathy And Advanced Heart Failure

GJA1-20k, the internally translated isoform of the gap junction protein Connexin-43 (Cx43) is required for trafficking of the full length Cx43 to the membrane. We recently found that GJA1-20k expression is reduced in patients and mice with arrhythmogenic cardiomyopathy (ACM), and that gene therapy-mediated introduction of GJA1-20k in a mouse model of ACM rescues Cx43 trafficking to the intercalated disc and reduces arrhythmia burden, indicating that loss of GJA1-20k contributes to arrhythmogenesis in ACM. Here, we examined cardiac muscle from patients with a confirmed diagnosis of ACM for GJA1-20k expression before and after left ventricular assist device (LVAD) support. The goal of this study was to determine if left ventricular (LV) unloading benefits endogenous expression of this critical trafficking protein. Cardiac tissue was collected from consecutive, prospectively enrolled patients undergoing LVAD implantation or heart transplantation in hospitals comprising the Utah Cardiac Recovery program and donor patients from hospitals throughout the Intermountain West. Samples were prepared for analysis using a standard lysis buffer and analyzed via Western Blotting using antibodies to GAPDH and Cx43-CT. Consistent with prior findings, cardiac muscle samples from patients with ACM had decreased GJA1-20k expression relative to muscle from healthy donor hearts not allocated for transplantation. However, tissue obtained from the same ACM patients post LVAD support (at the time of heart transplantation) revealed a large and significant increase in GJA1-20k expression compared to the pre LVAD timepoint (1 +/- 0.5 vs 10.2+/- 1, p=0.0013, n=3 ACM pre/post). In contrast to patients with ACM, patients with non-ischemic cardiomyopathy (NICM) that underwent LVAD implantation had no significant change in GJA1-20k expression after LV unloading (1+/- 0.5 vs 1.4+/- 0.7, p= 0.424, n=4 NICM pre/post). These data indicate that LV mechanical unloading increases GJA1-20k expression in hearts of patients with known ACM. Further work will focus on how mechanical unloading regulates GJA1-20k expression and whether mechanical unloading is sufficient to recover Cx43 trafficking and limit arrhythmias in ACM.

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

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. 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. 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. 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.

Use of left atrial appendage as an autologous tissue source for epicardial micrograft transplantation during LVAD implantation.

We report here the first clinical use of the left atrial appendage (LAA) for epicardial micrograft transplantation during left ventricular assist device (LVAD) implantation. Previously, a sample from the right atrial appendage (RAA) has been available for processing and administering micrograft therapy in cardiac surgery. Both LAA and RAA are rich sources of various types of myocardial cells and are capable of providing both paracrine and cellular support to the failing myocardium. The surgical approach of LAA micrografting facilitates epicardial micrograft therapy dose escalation and treatment of larger myocardial areas than done previously. Moreover, as collection of treated vs. untreated tissues from the recipient heart is possible following LVAD implantation at the time of heart transplantation, the evaluation of the therapy's mechanism of action can be further deciphered at cellular and molecular levels. This LAA modification of the epicardial micrografting technique has the overall potential to facilitate the adoption of cardiac cell therapy during heart surgery.

(27) Explainable Machine Learning to Improve Donor-Recipient Matching at Time of Heart Transplant

(27) Explainable Machine Learning to Improve Donor-Recipient Matching at Time of Heart Transplant

20-year angiographic patency of free internal thoracic artery graft at the time of heart transplant

Whether to accept a donor heart with coronary artery disease (CAD) remains controversial. Herein we report a 20-year of angiographic graft patency after concomitant coronary artery bypass grafting (CABG) at the time of heart transplantation.

Abstract 11515: Mannose-Binding Lectin is Dysregulated in Cardiac Endothelial Cells of Women With Peripartum Cardiomyopathy

Introduction: Peripartum cardiomyopathy (PPCM) is a type of heart failure that presents with systolic dysfunction in the third trimester of pregnancy or early postpartum. Viral myocarditis, genetic predisposition, and hormonal changes are suggested as contributing factors to PPCM. However, the molecular basis of PPCM remained elusive. Hypothesis: Cardiac expression of genes involved in immune system response is dysregulated in PPCM. Methods: We identified women with PPCM and age/race-matched heart donors from a dataset obtained from Myocardial Applied Genomics Network (MAGNet) consortium. Left ventricular (LV) biopsies were taken at the time of heart transplantation. Bulk RNA-seq was performed on LV tissue of patients with PPCM and non-failing heart donors (NF). We used the Human Cell Atlas (HCA) reference database with accession code ERP128138 to investigate cell-specific enrichment of genes. Results: Mean age of study participants was 36.1 years and 33.3% of participants had African American ancestry. We found that LCN6 (Log2(fold_change) = -4.1, p-val = 0.0027) and FCN3 (Log2(fold_change) = -3.4, p-val = 0.0042) are downregulated in LV tissue obtained from PPCM compared to NF. LCN6 encodes lipocalin-6 and FCN3 encodes ficolin-3 which are upstream of the mannose-binding lectin complement pathway. Based on HCA dataset on adult human hearts, we observed that LCN6 and FCN3 genes are mainly expressed by endothelial cells. Conclusions: We demonstrated that expression of LCN6 and FCN3 genes, which are upstream of the mannose-binding lectin pathway, is decreased in cardiac endothelial cells of individuals with PPCM. Mannose-binding lectin is a soluble pattern recognition receptor that identifies mannose and N-acetylglucosamine residues in a wide variety of pathogens and antigen-antibody complexes and works as an opsonin that facilitates phagocytosis. Our findings suggest the possibility of impaired immune complex clearance in PPCM pathogenesis.

Abstract 12713: Increased Calcium Sensitivity in Hypoplastic Left Heart Syndrome Hearts With Systolic Failure

Introduction: Systolic failure of the systemic right ventricle (RV) in children with hypoplastic left heart syndrome (HLHS) is a significant cause of death and a growing indication for heart transplantation. However, the underlying etiology of RV systolic failure in this population remains ill-defined. Hypothesis: We hypothesize that cardiomyocyte autonomous defects in contractility, characterized by increased calcium sensitivity, may contribute to systolic failure in HLHS. Methods: Explanted RV tissue was collected and flash frozen at the time of heart transplant in pediatric subjects with HLHS. HLHS subjects were classified by their primary indication for transplant: HLHS subjects with normal systolic function (HLHS-NF, N=2) were transplanted secondary to refractory protein losing enteropathy, and HLHS-F subjects (N=9) had end-stage heart failure due to decreased systolic function. Cardiomyocytes were isolated from frozen RV tissue, permeabilized, and glued to a force transducer and length controller. Force generated by the cardiomyocyte at different calcium concentrations was measured and force-calcium dose response curves were generated (modified Hill equation). pCa50 denotes the negative log of calcium concentration required to generate 50% maximal tension. Results: Less calcium is required to generate 50% maximal tension in HLHS-F cardiomyocytes (n=33 cardiomyocytes) when compared to HLHS-NF (n=5 cardiomyocytes), demonstrated by a higher pCa50 (5.62 vs. 5.46, p=0.027). Maximal force generation is similar between HLHS-NF and HLHS-F cardiomyocytes (55.5 mN/mm2 vs. 54.8 mN/mm2, p=0.96). Conclusions: Cardiomyocytes isolated from HLHS-F demonstrate increased calcium sensitivity when compared to those from HLHS-NF. Although future studies are needed, the presence of intrinsic alterations in sarcomeric properties in HLHS-F supports the hypothesis that cardiomyocyte autonomous defects may contribute to systolic failure in HLHS.

Validation of predicted heart mass equations by measurement of donor heart mass at time of heart transplantation.

Predicted heart mass (PHM) equations may be used in donor-recipient size matching in heart transplantation. We compared PHM and actual heart mass in 25 consecutive DBD heart transplants. There was a moderate positive correlation between actual heart mass and PHM. There was a similar moderate correlation between actual heart mass and donor weight or donor body surface area but not donor height. PHM was lower than actual heart mass for all donor hearts. Bland-Altman analysis showed a systematic bias between PHM and actual heart mass, with a mean difference of 190.9±66.4g. The utility of PHM equations is likely to be part of a multi-parametric assessment of the relative differences between donor and recipient, so the absolute difference is likely to be unimportant.

Interaction between donor obesity and prolonged donor ischemic time in heart transplantation

BackgroundThe purpose of the study was to determine the impact of donor obesity on outcomes following heart transplantation in the setting of routine (<4 h) and prolonged (≥4 h) organ ischemic times. MethodsRetrospective review of the 2000–2020 United Network for Organ Sharing Database was performed to identify adult heart transplant recipients and donors. Nearest-neighbor propensity score matching by donor obesity was performed separately among routine and prolonged cohorts, with Kaplan-Meier survival estimates used to assess survival at 5 years following transplantation. ResultsA total of 43,304 heart transplant recipients were included in analysis, with 15,925 (36.8 %) receiving obese donor hearts. After propensity-score matching, 30-day mortality and 5-year survival following transplantation were not statistically different between recipients of obese and non-obese donor hearts when organ ischemic times were routine. In the setting of prolonged organ ischemic times, those receiving obese donor hearts experienced lower 30-day mortality (5.1 % vs 6.7 %, p = 0.04) and improved 5-year survival (74.9 % vs 71.2 %, p < 0.01) compared to non-obese donor hearts. ConclusionsRecipients of obese donor hearts experienced improved outcomes compared to those receiving non-obese donor hearts when organ ischemic times exceeded 4 h. These findings suggest that the detrimental impact of prolonged organ ischemic time may be attenuated by donor obesity.

ACEi Use in Select Patients Awaiting Heart Transplant May Be a Risk Factor for the Development of Primary Graft Dysfunction and Vasoplegia

<h3>Purpose</h3> One of the most concerning issues immediately post-heart transplant (HTx) is the development of primary graft dysfunction (PGD) and/or vasoplegia. It has been suggested that patients on angiotensin-converting enzyme inhibitors (ACEi) are at risk for the development of PGD and vasoplegia due to activation of the kallikrein pathways which can activate bradykinin (vasodilator). It is not known whether ACEi with low systolic blood pressure (SBP) prior to HTx is associated with the development of PGD and vasoplegia. We sought to answer this question in our large, single center patient population. <h3>Methods</h3> Between 2017 and 2020, we assessed 189 patients awaiting HTx treated with ACEi (n=19) who had SBP less than 100 mmHg at the time of HTx and those patients without ACEi (n=170) but also with SBP less than 100 mmHg. Endpoints included the development of PGD (ISHLT grading scale) and vasoplegia (defined as requiring more than 2 vasoconstricting drugs with SBP still < 90 mmHg). A control group (n=176) of patients with SBP > 100mmHg was included for comparison. <h3>Results</h3> Patients treated with ACEi and with low SBP at the time of HTx appear to have significantly increased risk of PGD and vasoplegia development post-HTx. However, their 30-day and 1-year survival was no different compared to those patients not on ACEi (with low SBP) and those with normal blood pressure. (See table.) <h3>Conclusion</h3> ACEi and lower SBP at the time of heart transplantation may be a significant risk factor for the development of PGD and vasoplegia. Stopping ACEi prior to heart transplant may be warranted but requires further study.

Expanding the Diagnosis of Familial Dilated Cardiomyopathy among Heart Transplant Recipients with a Screening Instrument

<h3>Purpose</h3> Non-ischemic dilated cardiomyopathies (DCM) are important causes of heart transplant worldwide. Previous international data suggest that familial etiology for heart failure may be frequently overlooked among patients undergoing heart transplant. A structured screening instrument may help to identify patients who would benefit from genetic testing. <h3>Methods</h3> Fifty-nine heart transplanted patients from a single transplant center in South of Brazil were reviewed between 2015-2019; those with hypertrophic cardiomyopathies or confirmed ischemic DCM were excluded. Patients with non-ischemic CMP answered a structured screening questionnaire (Kushner et al., 2006), and familial etiology was classified in confirmed, probable, possible familial or non-familial DCM. <h3>Results</h3> Thirty-four heart transplant recipients were included (53% male, 85% Caucacian, 50±14 years). Etiologic classification pre and post structured screening is depicted in Figures 1A and 1B. There was a difference in suspected familial etiology pre and post structured screening (15% versus 32%; p = 0.037). <h3>Conclusion</h3> These findings suggest that familial DCM is frequently overlooked by the time of heart transplant. Our prevalence of familial DCM is similar to international reports. Applying a structured, low-cost, screening tool may contribute to counseling patients and their relatives regarding special attention to cardiovascular conditions and proper indication of genetic testing in a resource-limited scenario.

Heart Transplantation in Adult Congenital Patients Performed at a Pediatric Center: An Institutional Experience

<h3>Purpose</h3> Advancements in pediatric cardiovascular surgery have improved outcomes of children resulting in more adults with palliated congenital heart disease requiring a heart transplant. There is no standardized practice among adult congenital transplant centers for the location of pre- and posttransplant management of these patients. <h3>Methods</h3> We present the outcomes of 17 adult congenital transplantations performed at our pediatric institution from 2007-2021 as a joint evaluation and management effort between adult and pediatric programs, with pre, peri- and post-operative management occurring at the pediatric center. <h3>Results</h3> Patients aged 18-47 years at the time of heart transplantation. The most common indication for transplant was single ventricle with failing Fontan physiology, followed by DTGV with failing Mustard physiology. Two patients were retransplants for coronary artery vasculopathy. Patients listed were deemed candidates by both the pediatric and adult transplant teams. All patients were admitted prior to transplant at the pediatric hospital for initiation of inotropic therapy. The average pretransplant hospital stay was 76.9 days. Three patients required ECMO following transplant, for an average of 2 days. All patients received thymoglobulin immunosuppression and IV steroids. Maintenance immunosuppression was achieved with tacrolimus, mycophenolate mofetil, and oral steroid wean. Posttransplant length of stay averaged 15.8 days. All patients required temporary pacing. None required permanent pacing post-transplant. Most developed transient liver insufficiency and transient renal insufficiency. To date, 15/17 patients are living. One patient died of rejection at 22 months posttransplant and the other patient had massive post-transplant hemorrhage and developed mediastinitis, liver and renal failure and died 31 days posttransplant. The one year survival in this cohort was 94%. The three and five year survival is 88%. <h3>Conclusion</h3> We recommend a combined approach by adult and pediatric heart transplant teams when caring for adult congenital patients undergoing heart transplantation. Emphasis should be placed on the optimal location for congenital surgical management. Outcomes at or above the national adult heart transplant average can be achieved with such management in a high risk population.

Evaluation of Long-Term Kidney Function Following Orthotopic Heart Transplantation

Acute impairment of kidney function in patients with heart failure and heart transplantation is a frequent condition. However, the impact of the transplant on long-term kidney function remains controversial. This study describes a cohort of patients who received a heart transplant in a reference hospital between 2005 and 2019. Glomerular filtration rate during follow-up was calculated at 0, 6,12, 24, and 60 months using the Cockcroft-Gault and MDRD (modification of diet in renal disease study) equations. To identify changes we compared glomerular filtration rate (GFR) at baseline with measurements over time after heart transplantation, using a paired t test and a longitudinal model of Generalized Estimating Equations (GEE). Forty-four patients were included. The mean of baseline GFR was 67.9 ± 1.3 mL/min. A triple immunosuppressive therapy scheme was used with cyclosporine/tacrolimus, mycophenolate mofetil, and steroid, with progressive dose reduction. After adjusting for multiple variables, we found no reduction of GFR over time with the GEE model. There was no significant difference in GFR using Cockcroft-Gault equation at 6 (mean difference [MD] 4.46; confidence interval [CI] -2.1 to 11.09; P=0.18), 12 (MD 1.65, CI -4.5 to 7.82; P=0.59), 36 (MD 0.69; CI -6.04 to 7.43; P=0.83), and 60 months (MD 0.62; CI -5.5 to 6.79; P=0.83). Similar findings were found using MDRD equation. There is no significant GFR decline between the time of heart transplantation and a follow-up at 60 months. New studies are needed to evaluate changes in renal function beyond this timeframe.

De novo human leukocyte antigen allosensitization patterns in patients bridged to heart transplantation using left ventricular assist devices

IntroductionWe examined the impact and time course of de novo human leukocyte antigen (HLA) allosensitization following left ventricular assist device (LVAD) implantation. Methods and resultsForty patients had a calculated panel reactive antibody (cPRA) prior to LVAD surgery between January 2014 and December 2018. Of these patients, we retrospectively studied 33 patients who had pre-LVAD cPRA <10%. De novo allosensitization was defined as cPRA ≥10% within 3 months following LVAD surgery, and “persistent allosensitization” was defined as cPRA ≥10% at time of heart transplant or death. One-third (11/33) of our cohort developed de novo allosensitization within 3-months post-LVAD. Median duration of follow-up during LVAD support was 588 days (IQR 337–1071 days), or approximately 19 months. In an adjusted, multivariable analysis, female sex remained associated with de novo allosensitization (adjusted odds ratio [95%CI]: 11 (1.4–85), P = 0.026). De novo allosensitization was subsequently associated with persistent allosensitization (P = 0.024). Both axial-flow and centrifugal-flow LVADs had similar rates of allosensitization. Compared to those with no allosensitization, patients with de novo allosensitization did not appear to have inferior post-transplant outcomes of death or treated rejection. ConclusionIn our single-center experience, one-third of patients developed de novo allosensitization which did not appear to associate with inferior post-transplant outcomes. Female sex was associated with de novo allosensitization.

Cardiac myosin mechanochemistry underlies left ventricular dysfunction in human ischemic heart failure

Prolonged occlusion of the coronary arteries can lead to ischemic heart failure (IHF). Molecular changes within the myocardium during IHF are not fully understood. Accordingly, we aimed to characterize the biophysical properties of myocardial contractile proteins in IHF. Ten age-matched human males with similar BMI were included in the study. Cardiac biopsies of left ventricular free wall were taken from patients with ischemic heart failure (IHF, n=5) at the time of heart transplant or from organ donors with no previous history of ischemic heart failure (controls, n=5).

The effect of prolonged Intraaortic ballon pump (IABP) support on right ventricular function in end-stage heart failure

Abstract Introduction Right Ventricular (RV) function has prognostic implications in end-stage heart failure (ESHF) patients. RV failure following Left Ventricular Assist Device (LVAD) implantation increases morbidity and mortality. Achieving optimal RV function before LVAD implantation is of paramount importance. Purpose Purpose was to investigate the effect of Intra-aortic Balloon Pump (IABP) on RV function optimization in patients with bi-ventricular ESHF. Methods ESHF patients with poor RV function, presenting with acutely decompensated heart failure resistant to inotropes/vasopressors, thus requiring IABP for stabilization, were prospectively enrolled. Serum biochemistry, echocardiography and invasive hemodynamics were applied and eligibility for LVAD according to RV function was determined on the basis of pre-specified criteria (Right atrium Pressure (RAP) &amp;lt;12mmHg, Pulmonary Artery Pulsatility index (PAPi) &amp;gt;1.85, RAP/Pulmonary Capillary Wedge Pressure (PCWP) &amp;lt;0.67, RV strain &amp;lt;−14%). LV and RV tissue was harvested during LVAD or bi-ventricular mechanical circulatory implantation or at the time of heart transplantation. Fibrosis of the myocardial tissue was quantified. Results Sixteen patients aged 38±14 years were enrolled. Duration of IABP support was 62±50 (3–180) days. Three patients deteriorated requiring additional mechanical circulatory support. Two patients were stabilized without RV function improvement. In the remaining 11 patients, RV improved and fulfilled LVAD eligibility criteria (IABP responders); RA and RA/PCWP decreased from 18±6 to 10±4mmHg (p=0.0001) and from 0.60±0.19 to 0.42±0.11 (p=0.011) respectively. PAPi and RV strain improved from 1.46±0.65 to 3.20±0.58 (p=0.0001) and from −12.9±3.4% to −18.7±1.7% (p=0.0001) respectively. Significantly lower baseline NTproBNP and total bilirubin values were observed in the responders group. Six patients finally received LVAD and none suffered RV failure post-operatively (the remaining 5 were successfully transplanted). RV fibrosis correlated with post-IABP NTproBNP (r=0.91, p=0.001), total bilirubin (r=0.79, p=0.011), RAP (r=0.78, p=0.014), PAPi (r=−0.69, p=0.040), RAP/PCWP (r=0.74, p=0.022) and LV fibrosis (r=0.77, p=0.016), but not with baseline (pre-IABP) parameters. Conclusions Prolonged IABP support contributes to partial RV function recovery in patients with ESHF and bi-ventricular failure, thus leading to eligibility for LVAD implantation. RV fibrosis may predict RV response to IABP and post-IABP eligibility for LVAD. Funding Acknowledgement Type of funding sources: None.

Cardiac miRNAs were involved in the regulation of pathophysiological mechanisms underlying HF in pediatric patients after ventricular assist device implantation

Abstract Background VAD use in heart failure (HF) children have undergone rapid progress in the last three decades through pump technological innovation and improvement of perioperative care. Studies in HF adults showed that VAD put native heart at rest and lead to molecular changes in cardiac muscle, including at microRNA (miRNA) level. However, little is known on changes induced by VAD implant in cardiac miRNA expression and their putative targets in HF children. Purpose The aims of this study were to evaluate: 1) modification of miRNA expression in cardiac muscle from HF children after VAD support; 2) the putative targets of selected miRNAs by in silico analysis; 2) the role of the identify miRNAs on putative targets by in vitro study. Methods Cardiac biopsies were collected from HF children at the moment of VAD implant [n=8; 20 (7.5–64.5) months, 2 males; 19 (15.75–32.25) LVEF%] and at the time of heart transplant after VAD support [n=5; 32 (5–204) months; 4 males; 13.5 (10–18) LVEF%]. Cardiac miRNA expression was evaluated by NGS. The potential miRNA targets were identified by bioinformatics analyses and their cardiac expression by real-time PCR was evaluated. HL-1 cell line was used for testing the regulatory role of selected miRNA on predicted targets by miRNA mimic transfection study. Results At NGS, 465 miRNA were found on average in each sample and the cardiac expression levels of miR19a-3p, miR-1246 and miR-199b-5p decreased in HF children after VAD support compared to pre-implant (Fig. 1A-B). In silico analysis showed that more than 5000 potential gene targets regulated by miR-19a-3p, miR-1246 and miR-199b-5p. Among them, adiponectin receptors (AdipoR1, AdipoR2, T-CAD) were identified as common targets for 3 miRNAs. Real-time PCR data showed that levels of all adiponectin receptors increased significantly whilst the expression of 3 miRNAs decreased after VAD support (Fig. 1C). Moreover, AdipoR2 and T-CAD were inversely related to miRNA levels (Fig. 1D). In vitro studies confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2 (Fig. 1E-F), whilst only miR-199b-5p reduced the expression of T-CAD (Fig. 1G). Finally, AdipoR1 expression levels are not modified compared to control by miRNAs mimic transfection (data not shown). Conclusion In HF children the use of VAD could modify the expression of several miRNAs potentially involved in the regulation of several pathophysiological mechanisms underlying HF. Specifically, the reductions of miR-1246, mir-19a-3p, miR-199b-5p were associated with an increase of the adiponectin receptors AdipoR2 and T-CAD mRNA, suggesting the existence of a miRNAs related fine tuning of the adiponectin system at cardiac tissue level by VAD implant, able to favour the protective effect of adiponectin in HF cardiac muscle. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): FP7-ICT-2009 Project, Grant Agreement 24863 Figure 1

Mechanical ventilation at the time of heart transplantation and associations with clinical outcomes.

The impact of mechanical ventilation (MV) at the time of heart transplantation is not well understood. In addition, MV was recently removed as a criterion from the new US heart transplantation allocation system. We sought to assess for the association between MV at transplantation and 1-year mortality. We utilized the United Network for Organ Sharing database and included all adult, single organ heart transplantations from 1990 to 2019. We utilized multivariable logistic regression adjusting for demographics, comorbidities, and markers of clinical acuity. We identified 60 980 patients who underwent heart transplantation, 2.4% (n = 1431) of which required MV at transplantation. Ventilated patients were more likely to require temporary mechanical support, previous dialysis, and had a shorter median waitlist time (21 vs. 95 days, P < 0.001). At 1 year, the mortality was 33.7% (n = 484) for ventilated patients and 11.7% (n = 6967) for those not ventilated at the time of transplantation (log-rank P < 0.001). After multivariable adjustment, patients requiring MV continued to have a substantially higher 90-day [odds ratio (OR) 3.20, 95% confidence interval (CI): 2.79-3.66, P < 0.001] and 1-year mortality (OR 2.67, 95% CI: 2.36-3.03, P < 0.001). For those that survived to 90 days, the adjusted mortality at 1 year continued to be higher (OR 1.48, 95% CI: 1.16-1.89, P = 0.002). We found a strong association between the presence of MV at heart transplantation and 90-day and 1-year mortality. Future studies are needed to identify which patients requiring MV have reasonable outcomes, and which are associated with substantially poorer outcomes.