Purpose Analyze the characteristic of donors and recipients in our center and the results of heart transplantations for the two different levels of priority according to Italian previous allocation system, urgent patients and elective ones. Methods From 2006 to August 2020, 306 heart transplantations were performed at our institution. Of them 54 (17.6%) in urgency. Reasons for urgency were: 24 patients on ECMO support, 8 on IABP and 13 on intravenous inotropes, 4 arrhythmic storms and 5 complicated LVAD. Results In the urgent population, recipients were predominantly male (68.5 % vs 77.4 % in the elective p=0.17) and significantly younger (46.4 vs 52.2 years, p=0.001). More patients were on ECMO support (42.6% vs 1.7% p=0.000), IABP (42.6 vs 6.7% p=0.000) and mechanically ventilated (46.2% vs 6% p=0.000) pre transplant. The donors of urgent patients were younger than donors of the elective ones (38.9 vs 42.4 years (p=0.06). Donor's gender (68% males) and cause of brain death (brain trauma 44,4%, and cerebral hemorrhage 35,2%) were comparable in the two groups. Mean ischemic time was longer in urgent cases (211 vs 191 minutes, p=0.01) as donations came from across the whole country. Severe Early Graft Failure (EGF) requiring ECMO occurred in 9.4% of patients in the urgent population vs 3.6% in the elective with no significant difference (p=0.076), as well as in hospital mortality that was 11.5% in urgent vs 8.3% (p=0.429). Recipients' risk factors for in-hospital mortality were age [OR 1.05 (1.01;1.09), p=0.028] and Glomerular Filtration Rate (GFR) < 40 ml/min [2.68 (1.04;6.92), p=0.047]. No donors' variable resulted to be a risk factor for in-hospital mortality. Episodes and grade of rejection did not diverge between groups, and so did follow up mortality (16.7% in urgent vs 22.4% in electives p=0.444) Mean follow up time for urgent population was shorter (53.6 vs 75.6 months (p=0.007). Overall 5 and 10 years' mortality was 79.7% and 62% vs 88.1% and 72.8% for urgent and elective patients respectively (p=0.721). Conclusion This retrospective analysis of our transplantation activity with the different priority regimen shows little differences in terms of mortality and complications. Despite the worse clinical characteristics of the urgent recipients and the longer ischemic time, results do not significantly differ from the elective population, underlying the importance of donation quality.

Purpose The evaluation of graft function after heart transplantation (HT) is made by echo and endomyocardial biopsies (EMB). In our Center, we regularly perform right heart catheterization (RHC) at every EMB, until 5 years after HT. The aim of this study is to investigate the role of RHC for defining graft function. Methods We included in this study all patients (pts) undergoing to a EMB after the first month from HT for standard monitoring or for symptoms after 5 yrs from HT in our Center in 2016-17. Data were collected at every EMB. The endpoints were the interplay between RHC, LVEF and biopsy, and the impact of RHC on 2-yrs MACE occurrence. The follow up was started after the first abnormal RHC or, if no abnormal values were found, after the last RHC performed in the observation period. Results 586 EMBs were performed in 113 pts (56.6% <1yr, 38.6% 1-5 yrs, 4.8% for symptoms >5 yrs from HT). In the routine EMBs, 3A CMR and pAMR-2 were more frequent in the first year (18.4% vs 5.8%, 2.4% vs 0.4%, p<0.05); in the unscheduled EMBs, only 10.7% were 3A while 29% were p-AMR+ (25% pAMR-1+, 4% pAMR-2). LVEF did not differ according to distance from HT, routine vs unplanned EMB or CMR grading, but it was more frequently lower in pAMR+ (65% vs 7%) (p<0.01) .RHC better correlated with EMB results, being more frequently pathologic in 1B vs 3A/3B and other grades (46% vs 39% vs 32% respectively, p=0.06) and in AMR (32% vs 51% vs 93%, p-AMR 0 vs 1 vs 2, p<0.01). LVEF was less frequently normal in pts with abnormal RHC, but 82% of pts with a pathologic RHC had normal LVEF. We established three hemodynamic phenotypes: diastolic dysfunction (high filling pressures, normal cardiac index); low cardiac index; normal values. Diastolic dysfunction was more frequent according to pAMR grading (9% vs 29% vs 50%, p=0.01); low CI was more frequent in pAMR+ vs pAMR- (12% vs 8%, p=0.01); no specific hemodynamic pattern was associated with CAV. The incidence of MACE was highest in pts with a pathologic RHC and a 1B/3A/3B, lowest in those with normal RHC and EMBs positive and intermediate in those with a negative biopsy, regardless of RHC values (37.0± 11% vs 16.5±4% vs 0%). Conclusion Hemodynamics better correlates to histology than LVEF and helps in stratifying prognosis in patients with rejection; 1B and >3A CMR can both impact prognosis; assessment of diastolic dysfunction may help in suspecting latent pAMR. Our results support the use of RHC in the complex assessment of graft function. The evaluation of graft function after heart transplantation (HT) is made by echo and endomyocardial biopsies (EMB). In our Center, we regularly perform right heart catheterization (RHC) at every EMB, until 5 years after HT. The aim of this study is to investigate the role of RHC for defining graft function. We included in this study all patients (pts) undergoing to a EMB after the first month from HT for standard monitoring or for symptoms after 5 yrs from HT in our Center in 2016-17. Data were collected at every EMB. The endpoints were the interplay between RHC, LVEF and biopsy, and the impact of RHC on 2-yrs MACE occurrence. The follow up was started after the first abnormal RHC or, if no abnormal values were found, after the last RHC performed in the observation period. 586 EMBs were performed in 113 pts (56.6% <1yr, 38.6% 1-5 yrs, 4.8% for symptoms >5 yrs from HT). In the routine EMBs, 3A CMR and pAMR-2 were more frequent in the first year (18.4% vs 5.8%, 2.4% vs 0.4%, p<0.05); in the unscheduled EMBs, only 10.7% were 3A while 29% were p-AMR+ (25% pAMR-1+, 4% pAMR-2). LVEF did not differ according to distance from HT, routine vs unplanned EMB or CMR grading, but it was more frequently lower in pAMR+ (65% vs 7%) (p<0.01) .RHC better correlated with EMB results, being more frequently pathologic in 1B vs 3A/3B and other grades (46% vs 39% vs 32% respectively, p=0.06) and in AMR (32% vs 51% vs 93%, p-AMR 0 vs 1 vs 2, p<0.01). LVEF was less frequently normal in pts with abnormal RHC, but 82% of pts with a pathologic RHC had normal LVEF. We established three hemodynamic phenotypes: diastolic dysfunction (high filling pressures, normal cardiac index); low cardiac index; normal values. Diastolic dysfunction was more frequent according to pAMR grading (9% vs 29% vs 50%, p=0.01); low CI was more frequent in pAMR+ vs pAMR- (12% vs 8%, p=0.01); no specific hemodynamic pattern was associated with CAV. The incidence of MACE was highest in pts with a pathologic RHC and a 1B/3A/3B, lowest in those with normal RHC and EMBs positive and intermediate in those with a negative biopsy, regardless of RHC values (37.0± 11% vs 16.5±4% vs 0%). Hemodynamics better correlates to histology than LVEF and helps in stratifying prognosis in patients with rejection; 1B and >3A CMR can both impact prognosis; assessment of diastolic dysfunction may help in suspecting latent pAMR. Our results support the use of RHC in the complex assessment of graft function.

transplant activity for each financial year up to April 2020 and our activity between Jan -27 th May 2020 (the first UK pandemic peak) comparing this to the same period over the last five years.This allowed us to directly compare the effect of COVID with previous years activity.Results: A total of 19 heart patients died during Jan to 27 th May 2020.Out of the total deaths 4 were from paediatric group, 11 were post-transplant and 5 on the active list.There were no cardiac deaths related to COVID 19.The total deaths during the same period were 19, 24, 20 and 32 in the years 2019, 2018, 2017 and 2016 respectively.A total of 41 lung patients died during Jan to 27 th May 2020.Out of the total 11 were on the active list awaiting transplant and 19 were post-transplant deaths.Of these 2 were COVID deaths.The corresponding deaths during year 2019, 2018, 2017 and 2016 were 46, 51, 49 and 46 respectively.Transplant activity from Jan to 27 th May in 2016-19 averaged 32 (16 hearts,16 lungs); activity during the same time period in 2020 was 4 lungs and 13 hearts, clearly affected by reduced activity due to COVID19.Conclusion: This audit does not suggest a significant rise in mortality due to the COVID 19 pandemic in vulnerable patients either pre or post-transplantation. Measures such as shielding were highly effective in this population.Transplant activity for the year was affected.

PT-INR data before and after the event, and interruption period in each group were shown in the table.The level of PT-INR after the reversal of anticoagulation therapy was significantly different in the severity of bleeding.There were no thromboembolism events relating to reversal and interruption, as well as de novo bleeding after the resumption.Conclusion: This result suggested that proper evaluation and classification of hemorrhage events may contribute to the appropriate reversal or interruption of antithrombotic therapy for VAD-related hemorrhage.

The assessment of right ventricular afterload through evaluation of pulmonary artery elastance seems to better stratify than PVR the need of HT in patients with severe heart failure. Treatments directed to a reduction of PAWP can significantly modify elastance, especially in pts with high resistive afterload.

Our study shows that LCZ696 improves hemodynamic profile and symptoms in pts with advanced HF by reducing pulmonary and left ventricular filling pressures. This effect seems to be dose-independent. Our results suggest that LCZ696 can lead to a significant clinical and hemodynamic improvement even at low doses.

Purpose Little is known about the role of ECG in heart transplanted (HT) patients (pts). In this study, we sought to identify ECG parameters that could help to identify graft dysfunction and to stratify prognosis. Methods Pts enrolled in a prospective study aimed to test a novel immune monitoring test (Quantiferon monitor), consecutively coming at our Clinic (2014-17) constituted study cohort. We created 3 groups: A) normal graft function (HT<2 yrs); B) normal graft function (HT >5 yrs); C) LVEF<50% or symptoms of heart failure. ECG data collected at the enrolling visit were: PQ, QRS width, QTc (Bazett's formula), heart rate, rhythm, conduction disorders. The endpoint was the 3-yrs combined survival from cardiovascular death and MACE. Results Among 153 pts (58±14 yrs, 75%M), 79% had normal graft function (51% A, 28% B). Pts with graft dysfunction (21%), compared with groups A and B respectively, had a different distance from HT (1.2±1.6 vs 15.7±5.7 vs 12.9±7.4 yrs), more frequently CAV (8.8% vs 14.9% vs 64%), longer PQ (181±53 vs 163±38 vs 148±25 ms), wider QRS (131±34 vs 105±18 vs 101±18 ms), longer QTc (473±5 vs 445±4 vs 453±3 ms), more conduction disorders (75% vs 51.2% vs 39.2%) and Afib (9.1% vs 0 vs 4.6%), p≤ 0.01 for all; heart rate was intermediate between A and B. Distance from HT (i.e. >5yrs) and, similarly, CAV, carried a longer PQ, wider QRS, more conduction disturbances (p<0.01 all), but no differences in QTc (p=0.30 and p=0.15 respectively). CAV pts had lower voltages. MACE occurrence was higher in group C, similar in the other two groups (61.6±9.0% vs 92.0±4.5% vs 94.7±2.6%,p<0.001). At multivariate analysis, QTc ≥470 ms (ROC derived) (HR:3.1, p=0.01) and CAV (HR:6.1, p<0.01) independently predicted MACE, after adjusting for distance from HT(Fig). Conclusion ECG parameters in HT are influenced by many factors, reflecting multiple pathways leading to graft dysfunction. QTc may be a marker of subclinical systolic dysfunction (i.e. microvascular disease, chronic rejection) and help in identifying high risk pts.

Purpose Pulmonary hypertension (PH) is frequent in HT candidates; identifying patients (pts) with urgent need of HT is challenging. Guidelines suggest diastolic transpulmonary gradient (DPG) ≥ 7 mmHg to differentiate combined (CpC) and isolated (IpC) post-capillary PH, but its clinical relevance in this setting is unknown. The aim of our study is to analyze the prognostic impact of PH classification in pts referred for HT, and the interplay of CpC and IpC with markers of ventricular function. Methods We included all pts evaluated for HT in our Center (2002-17) undergoing to a right heart cath, collecting data at first evaluation. We created 3 groups: no- PH, IpC-PH (mean PAP > 25 mmHg, PVR<3 WU), CpC-PH (mean PAP>25 mmHg, PVR ≥3 WU and/or DPG≥7 mmHg). Pulmonary artery pulsatility index (PAPi) was analyzed as marker of RV function. The endpoint was the combined incidence of death on the waiting list or urgent HT (1-and 2-yrs survival rates). Results Among the overall cohort of 566 pts (53± 11y, 83% M, 45% DCM, 40% CAD), 59.5% had PH: 31.8% IpC-PH, 27.7% CpC-PH. The endpoint was more frequent in the PH subgroups at 1 and 2 yrs (p<0.01). 10 pts (0.2%) had DPG≥ 7, one with PVR<3. Although CpC definition identified pts at worse prognosis, DPG≥7 did not predict outcome at 1 or 2 yrs; at multivariate analysis, PVR≥ 3 and PAPi < 3.8 (median) were the only independent predictors of the endpoint both at 1 (HRs:1.9;2.8) and 2 yrs (HRs: 1.9;3.1), (all p<0.03), even adjusting for clinical variables. Lower PAPi values carried an higher risk early (at 1 yr) in CpC-PH group (65.6±7.0% vs 88.1±3.7%,p<0.01), and later (at 2 yrs) in IpC-PH group (73.7±5.7% vs 87.9±4.8%,p=0.01); mortality at 2 yrs in IpC-PH with low PAPi was similar to CpC-PH with higher PAPi (Fig). Conclusion Our study shows that current definition of CpC and IpC in type 2 PH stratifies prognosis in HT candidates, but DPG is epidemiologically irrelevant and doesn't increase diagnostic accuracy. Adding an indirect marker of RV function (PAPi) to PVR assessment could predict better the need for HT. Pulmonary hypertension (PH) is frequent in HT candidates; identifying patients (pts) with urgent need of HT is challenging. Guidelines suggest diastolic transpulmonary gradient (DPG) ≥ 7 mmHg to differentiate combined (CpC) and isolated (IpC) post-capillary PH, but its clinical relevance in this setting is unknown. The aim of our study is to analyze the prognostic impact of PH classification in pts referred for HT, and the interplay of CpC and IpC with markers of ventricular function. We included all pts evaluated for HT in our Center (2002-17) undergoing to a right heart cath, collecting data at first evaluation. We created 3 groups: no- PH, IpC-PH (mean PAP > 25 mmHg, PVR<3 WU), CpC-PH (mean PAP>25 mmHg, PVR ≥3 WU and/or DPG≥7 mmHg). Pulmonary artery pulsatility index (PAPi) was analyzed as marker of RV function. The endpoint was the combined incidence of death on the waiting list or urgent HT (1-and 2-yrs survival rates). Among the overall cohort of 566 pts (53± 11y, 83% M, 45% DCM, 40% CAD), 59.5% had PH: 31.8% IpC-PH, 27.7% CpC-PH. The endpoint was more frequent in the PH subgroups at 1 and 2 yrs (p<0.01). 10 pts (0.2%) had DPG≥ 7, one with PVR<3. Although CpC definition identified pts at worse prognosis, DPG≥7 did not predict outcome at 1 or 2 yrs; at multivariate analysis, PVR≥ 3 and PAPi < 3.8 (median) were the only independent predictors of the endpoint both at 1 (HRs:1.9;2.8) and 2 yrs (HRs: 1.9;3.1), (all p<0.03), even adjusting for clinical variables. Lower PAPi values carried an higher risk early (at 1 yr) in CpC-PH group (65.6±7.0% vs 88.1±3.7%,p<0.01), and later (at 2 yrs) in IpC-PH group (73.7±5.7% vs 87.9±4.8%,p=0.01); mortality at 2 yrs in IpC-PH with low PAPi was similar to CpC-PH with higher PAPi (Fig). Our study shows that current definition of CpC and IpC in type 2 PH stratifies prognosis in HT candidates, but DPG is epidemiologically irrelevant and doesn't increase diagnostic accuracy. Adding an indirect marker of RV function (PAPi) to PVR assessment could predict better the need for HT.

Abstract Background Pulmonary hypertension (PH) is an important prognostic marker among patients (pts) with heart failure. Recent ESC guidelines have introduced the concept of diastolic transpulmonary gradient (DPG) to differentiate combined (CpC) and isolated (IpC) post-capillary PH. However, its validation in a setting of patients evaluated for heart transplantation (HT) has been poorly explored; moreover, it doesn't incorporate right ventricular (RV) function. Purpose To analyze the prognostic role of current classification of PH and its interplay with RV function and diuretic therapy in pts with advanced heart failure referred for HT. Methods We included all pts evaluated for HT in our Center (2002–16) undergoing to a right heart cath (RHC), collecting data at first evaluation. Patients were divided into three groups: no PH (mPAP<25 mmHg), IpC-PH (mean PAP >25 mmHg, PVR<3 WU), CpC-PH (mean PAP>25 mmHg, PVR ≥3 WU and/or DPG ≥7 mmHg). Pulmonary artery pulsatility index (PAPi) was analyzed as a marker of RV function; oral furosemide>125 mg/day (median value) or i.v. diuretics/dialysis were considered as high-dose diuretics (HDD). The study endpoint was the combined incidence of death or need for high urgent HT, expressed as 2-yrs survival rate. Results Among the overall cohort of 458 pts (53.1±10.9 yrs, 82,6% males, 40.3% CAD, 9.3% on IABP), 57.9% had PH: 30.8% IpC-PH, 27.1% CpC-PH. Only 8 pts (0.2%) had DPG≥7, one with PVR<3. The use of HDD differed significantly according to PH classes (44.6% vs 56.3% vs 68.3%, no PH vs IpC vs CpC-PH respectively, p<0.01) and was associated with a worse outcome (p<0.01). The incidence of the primary endpoint in the overall cohort was 74.1±2.5%. While pts with CpC-PH had the worst prognosis, DPG≥7 did not predict the primary endpoint. At multivariate analysis, PVR ≥3 WU (HR: 16.7), PAPi <3.8 (median value, HR: 4.1), HDD (HR: 5.6) were independent predictors of the primary endpoint, (p<0.04 for all) as well as need for IABP (HR: 19.0, p<0.01), even adjusting for clinical variables. Lower PAPi values carried an higher risk at 2 years both in IpC and CpC PH groups, thus allowing to better stratify the need for urgent HT (81.6±6.6% vs 78.6±5.7% vs 67.3±6.7% vs 49.1±7.9% respectively, p<0.001) (Fig.1). Figure 1 Conclusion Our results suggest that, even if current definition of type 2 PH predicts the need of urgent HT, the incorporation of DPG ≥7 is epidemiologically irrelevant and doesn't increase accuracy, whereas combining an indirect marker of RV function (PAPi) with PVR assessment, even correcting for diuretic therapy, could help to better stratify the need of a rare resource like HT in patients with advanced heart failure and pulmonary hypertension.

Purpose Gene expression profiling (GEP) of endomyocardial biopsies (EMB) by the MMDx system has been shown to estimate the probability of T-cell mediated (TCMR) and antibody-mediated rejection (AMR), improving the histology-based diagnoses in heart transplant (HT) recipients. Second generation analysis allowed to identify an additional phenotype characterised by molecules related to tissue injury (INJ), such as de-differentiation pathways, macrophages transcripts, and heart transcripts. The clinical correlates of this novel profile and its association with ISHLT pathology grading is under development. In this study we analyse the association of MMDx novel profiles with cardiac function and with ISHLT grades for TCMR and AMR. Methods 254 EMBs from 121 patients were analysed with MMDx platform. EMBs were performed according to standard protocol during the first 5 years after transplant and by clinical indication later on. Right heart catheretization was performed at the time of EMB, which were graded by 1990 and 2006 ISHLT classifications for TCMR and 2014 guidelines for AMR. Results Prevalence of molecular phenotypes varied during time course: INJ was frequent in the first months, absent during the first 5 years, and rose again in late for-cause EMBs; AMR peaked early and late after transplant, in line with DSA time-course; TCMR probability was meaningful in the early months only. Cardiac function also varied across the three profiles: INJ was significantly associated with low cardiac index (CI) and high right atrial pressure, AMR with elevated wedge pressure and low CI, and TCMR with low CI only. Overall, GEP was in agreement with pathology readings in most cases, being normal in 90% of the 0 graded EMB, and abnormal in over 70% of the 2R or pAMR2. While current 1R grade showed abnormal GEP only in 37% of cases, the old 1B grade had abnormal GEP in 60% of cases, mostly associated with AMR profile. INJ profile was found in 54% of the 2R or greater EMBs. Conclusion GEP reveals variable molecular patterns during transplant time course; INJ phenotype appears associated mainly with low CI in the context of post-operative injury and severe mixed rejection, while AMR seems to increase markers of graft stiffness. Despite good overall agreement with pathology readings, current ISHLT grading is inaccurate, with the “old” 1B grade being highly associated with AMR molecular profiling.

Equity in heart transplantation (HT) is crucial; while prioritization basing on clinical urgency may favor access to HT for high risk patients (pts), an approach based on predicted post-HT survival may lead to better outcomes. The aim of the present study is to investigate differences in survival gain related to HT according to different risk factors of pts in the waiting list (WL).

Endomyocardial biopsy (EMB) is the standard of practice for diagnosis of rejection in heart transplant. However, reproducibility of EMB pathology reading (pEMB) may yield to high diagnostic variability, questioning its overall accuracy. In addition, correlation of current grading of pEMB with clinical phenotypes also is uncertain. Seeking to improve the precision in rejection diagnosis and to guide the interpretation of pEMB, we used a microarray-based analysis to identify molecular phenotypes (MP) associated with rejection.

Risk factors for post-HT mortality are known; however, the degree of risk associated with them may vary by recipient age. The aim of this study was to investigate the different weight of comorbidities and of continuous flow (CF) LVAD use across age groups in a contemporary patient cohort.

The purpose of this investigation was to assess the prognostic impact of pre-transplant pulmonary hypertension (PH) grading on early- to long-term hemodynamics, right venticular graft function and survival after heart transplantation (Htx).