Background and aim In heart transplant (HT) recipients, early alterations of graft function are often asymptomatic and, therefore, underrecognized. The investigation of ventricular-vascular interaction could identify poor outcomes in HT recipients with normal left ventricular ejection fraction (LVEF). We compared pressure-volume (PV) derivative variables between HT patients and healthy controls. Additionally, we assessed the influence of ventricular-arterial coupling (VAC) and its components on long-term outcome. Methods in this single-center retrospective observational cohort study, HT patients surviving their first post-HT year with LVEF ≥50%, absence of allograft vasculopathy and acute rejection were enrolled. VAC and other PV derived parameters were measured by transthoracic Doppler echocardiography and then compared with healthy controls, matched for age and sex. The endpoint was cardiovascular mortality after the first year from HT. Results: from 1985 to 2015, 345 patients were enrolled. Arterial elastance (Ea) and ventricular elastance (Ees) were higher in HT recipients than in healthy controls (4.03 vs. 1.65, p<;0.0001 and 6.75 vs 2.47, p<0.0001, respectively), while VAC was similar between the two groups (0.66 vs. 0.59, p=0.105). Cardiac energetic parameters (stroke work, potential energy, PV area) were significantly reduced in HT patients. After a median of 11.3-year follow-up, 59 (17%) HT recipients died. VAC was not significantly associated with cardiac mortality (p=0.074). Conversely, survival was lower in HT recipients with Ea<4 mmHg/mL and Ees≤6.75 mmHg/mL, and both were independently associated with mortality risk after adjustment (Ea > 4 mmHg/mL: HR 2.25 [95% CI 1.38–3.66], p = 0.013; Ees ≤ 6.75 mmHg/mL: HR 3.70 [95% CI 1.95–7.06], p = 0.001). Conclusions In HT recipients with normal LVEF, high Ea and low Ees values were independently associated with poorer outcomes in a long-term follow up. Conflict of Interest None

Abstract Background Cardiac physiology changes after heart transplant (HT), resulting in a restrictive physiology with an increase in both arterial elastance (Ea) and ventricular elastance (Ees). This leads to a higher susceptibility to develop afterload mismatch, although the early identification of this phenomenon has not yet been explored. The aim of this study is to identify the presence of afterload mismatch after HT, its determinants, and its impact on cardiac mortality. Methods We conducted an observational, single-centre study based on the historical cohort of patients who underwent HT from 1985 to 2015 at our institution. We included patients who had survived the first year after HT with left ventricular ejection fraction (LVEF) ≥ 50%, International Society of Heart and Lung Transplantation (ISHLT) cardiac allograft vasculopathy of grade 0-1, and ISHLT acute cellular rejection of grade 0-1R at 1 year after HT. Ea and Ees were calculated using a non-invasive method based on blood pressure and end-systolic volume and end-diastolic volume measured at transthoracic echocardiography. Patients were grouped in 3 categories according to the presence of increased afterload and afterload mismatch as follows: low afterload (LA - Ea lower the median), matched high afterload (MHA - Ea higher of equal than the median, Ees higher or equal than the median), afterload mismatch (AM - Ea higher or equal than the median, Ees lower than the median). The impact of AM on long-term outcome, defined as cardiac mortality, was investigated, as well as predictors of AM. Results The study cohort consisted of 345 HT patients. The median of Ea and Ees were 4.0mmHg/mL and 6.75mmHg/mL, respectively. 49 patients (13%) developed AM, while LA and MHA groups accounted for 49% and 36% of the cohort, respectively. Patients with AM were mostly male (91%), with ischemic heart disease (45%) and a higher percentage of left ventricular assisted device prior to HT (8%). LVEF was lower in AM (57% vs 63% and 64% for LA and MHA respectively, p < 0.0001), while stroke volume was lower than LA and similar to MHA (27ml vs 35mL and 26mL for LA and MHA respectively, p = 0.0001). Predictors of AM were male recipient from male donor (Mr/Md) (β 015, p = 0.0067) and Mr from female donor (Mr/Fd) (β 0.6, p = 0.0078). After a median of 11.3-year follow-up, 59 (17%) HT recipients died. Cardiac mortality was higher in AM than in the other groups (AM median survival 17.2y vs 27.8y and 24.1y for LA and MHA respectively, log-rank p = 0.005). After adjusting for confounding variables, AM was a predictor of cardiac mortality (HR: 2.26; 95%CI 1.18 – 4.35), such as Mr/Fd (HR 2.94; 95%CI 1.18 – 4.35, p = 0.0358). Conclusion AM, in the context of a normal LVEF, is associated with male donor and sex mismatch, and negatively affects long-term outcome after HT.KM curvesCox proportional hazard model

Introduction: Coronary Computed Tomography Angiography (CCTA) represents a promising non-invasive alternative for evaluating Coronary Allograft Vasculopathy (CAV) in patients undergoing orthotopic heart transplantation (OHT), offering clinical and economic advantages over traditional invasive techniques.

Abstract Background The Prognosis after ST-elevation myocardial infarction (STEMI) remains poor. Angiotensin-II and endothelin-1 contribute to adverse prognosis after STEMI through molecular mechanisms that lead to myocardial inflammation, fibrosis and, ultimately, adverse myocardial remodeling. Functional autoantibodies against angiotensin II type 1 (AT1R-AAs) and endothelin-1 type A (ETAR-AAs) receptors bind to the same receptors as natural ligands, eliciting similar (and amplified) responses. In patients with STEMI, AT1R-AAs and ETAR-AAs have been associated with a higher risk of developing microvascular obstruction and left ventricular remodeling. Both microvascular obstruction and left ventricular remodeling are associated with a poor prognosis. Purpose To assess the prognostic role of AT1R-AAs and ETAR-AAs after STEMI. Methods Consecutive STEMI patients who underwent primary percutaneous coronary intervention within 12 h after pain onset were enrolled in this prospective study. The levels of AT1R-AAs and ETAR ETAR-AAs at the time of hospital admission were measured using an enzyme-linked immunosorbent assay (ELISA) in all patients. The incidence of major adverse cardiovascular events (MACE, defined as a composite of cardiovascular mortality, myocardial re-infarction, and hospitalizations for heart failure) during follow-up was the primary outcome. Autoantibody seropositivity was defined according to ELISA’s kit manufacturer’s instructions (levels > 10 U/mL). Results Two hundred patients with STEMI were enrolled. The baseline characteristics of the patients are shown in Table 1. Of these, 110 (55%) were seronegative for both autoantibodies, 44 (22%) were seropositive for one autoantibody (but not both), and 46 (23%) were seropositive for both autoantibodies. The incidence of MACE over a 14-month median follow-up was higher in patients with double (31%) and single (25%) seropositivity than in seronegative patients (13%, p=0.009 and p=0.06, respectively). Survival free from MACE was significantly different across the different degrees of autoantibody seropositivity (Figure 1). In the multivariable Cox regression analysis, adjusted for the variables that were significant in the univariate analysis (highlighted in bold in Table 1), double seropositivity was independently associated with an increased risk of MACE (hazard ratio 2.386, 95 % CI 1.471-3.864, p<0.001). Conclusions The degree of seropositivity for AT1R-AAs and ETAR-AAs is associated with an increased risk of MACE after STEMI. Our findings provide valuable mechanistic insights into the pathophysiology of STEMI and pave the way for future therapies focused on the improvement of long-term prognosis after acute coronary syndromes.

Purpose The aim of our study is to investigate a possible transcriptomic signature to discriminate the inflammatory infiltrate observed in monitoring endomyocardial biopsies (EMBs) in post-transplanted patients with or without Citomegalovirus (CMV) viremia. Methods We selected 16 patients who underwent cardiac transplantation in our centre between January 2018 and December 2020 and monitored for CMV infection and allograft rejection. We identified three groups: a control group (n=5) with patients negative at BEM for rejection and CMV infection, a rejection group (n=5) with patients positive at BEM for Acute Cellular Rejection (ACR, ≥3A-2R ISHLT grade) but negative for CMV viremia and an infection group (n=6) with patients positive at BEM for ACR (≥1A-1R ISHLT grade) in the setting of CMV viremia (>1000 copies/mL).We extracted total RNA from FFPE-EMBs and performed a transcriptome profiling by a microarray platform (Clariom-S) without any bias of transcript selection. Then, we analysed the messenger RNA profile using TAC (Transcriptome Analysis Console) software. Results The bioinformatic analysis showed differential expressed genes among the three groups (gene level fold change <-2 or >2). Notably, 293 genes were differentially expressed between Control and Infection groups (82 up-regulated and 211 down-regulated), 407 genes between Control and Rejection groups (126 up-regulated and 281 down-regulated) and 18 genes between Infection and Rejection groups (10 up-regulated and 8 down-regulated) (p-value <0.005). After, we investigated the role of the single genes, identified in the latter comparison, that could discriminate between infection and rejection in WikiPathways. This analysis revealed that these genes are mainly involved in cardiomyocytes metabolism, Il-7 signalling, regulatory circuits of the STAT3 signalling, DNA replication and cardiac progenitor differentiation pathways. Conclusion This is a first explorative but promising analysis that identified new transcriptomic signatures that could discriminate between rejection and infection in post cardiac transplant follow-up.

Purpose The aim of our study is to assess the reliability of transcriptome profile platform outcomes between different tissue preservation conditions, RNA extraction methods and heart-failure-related genes, minimizing intra- and inter-experimental variability. Methods Our cohort of study is composed by 6 FFPE endomyocardial biopsies (EMBs) and 6 fresh frozen (FF) heart tissues samples belonging to the same adult end-stage heart failure patient, limiting inter-patient variability bias. Two major RNA extraction procedure were tested for FF and FFPE tissues. Then, we performed a high-throughput microarray expression profiling without a bias of transcript selection. We analyzed mRNAs expression through R programming and transcriptome analysis software, exploring >20000 transcripts. We refined the transcriptome analysis selecting, from a literature systematic review appraisal 30 heart-failure related genes, coupling the overlapping genes in the differential expression and network analysis. Results We compared the analysis of up- and down-regulated genes between the groups, addressing both the different RNA extraction procedure and tissue preservation, while sharing the same transcriptome platform. The differential expressed genes (DEG) analyzed had fold change set at 2 and -2, and a cut-off threshold of FDR adjusted p-value < 0,05. Heatmap showed a great samples' clusterization according to preservation and extraction methods. Only 284 genes passed filter criteria in FFPE inter-groups comparison of extraction methods, while 52 differed in FFPE vs. FF, showing a great overlap of transcriptome signature, corroborated by the heart-failure related set of genes. The network analysis highlighted that most of the DEG are strongly associated (p-value adjusted <0.004) to the dysregulation of reticulum and collagen related cell component, in accordance with heart failure stage. Conclusion To the best of our knowledge, this is the first study in heart transplantation fields comparing genetic extraction and preservation methods for microarray expression profile evaluation correlated with pathophysiological mechanism. A proof of concept that RNAs from FFPE-EMBs, and not only FF, are feasible for microarray expression profile evaluation, and derived transcriptome profiles have a strong potential for research and diagnostic clinical application.

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk stratification of patients with nonischemic dilated cardiomyopathy (NIDCM) is challenging. Machine learning (ML) models represent novel technologic tools that promise to improve predictive ability of cardiovascular adverse outcomes. Purpose To implement two ML models to predict the risk of adverse outcome (composite endpoint of all-cause death, heart transplantation, implantation of ventricular assistant device), in patients with NIDCM using clinical and radiological data. Methods We retrospective collected data from patients affected by NIDCM referred to our cardiologic unit between 2002 and 2018. Two ML models, an extreme gradient boosting machine (XGBoost) and an artificial neural network (ANN), were developed using cardiovascular magnetic resonance (CMR) and clinical parameters. Both models were trained on 67% of patients and evaluated based on the other 33% as internal validation. To investigate the contribution of different features in our models, we used Shapley additive explanations (SHAP) analysis. Results The final cohort resulted of 161 patients (mean age 48.9±13.6 years, 71% males), with a mean follow up duration of 79.1 months. During the follow-up 29 adverse event were observed (16 deaths, 12 heart transplantation, 1 implantation of ventricular assistant device). ANN model resulted in an accuracy of 76% with an area under the receiver operating characteristic (ROC) curve of 0.66; SHAP analysis identified male sex, percentage of late gadolinium enhancement (LGE) and LGE distribution in the lateral wall of myocardium as the main markers of adverse outcomes. XGBoost model resulted in an accuracy of 78% with a ROC curve of 0.76; SHAP analysis identified NT-proBNP level, age and serum creatinine mainly related with adverse outcomes. About CMR parameters, left ventricular diameter and ejection fraction better related with adverse outcomes. Conclusions Our models achieved a good performance in prediction of adverse events, suggesting that ML could improve our ability of risk stratification of NIDCM. XGBoost better performed than ANN, and SHAP analysis suggested that both CMR parameters and clinical parameters contribute to the definition of risk. ANN performance and SHAP analysisXGBoost performance and SHAP analysis

normothermic temperatures, however, may aggravate graft injury, especially in endothelial cells.We hypothesized that replacing CSS with hypothermic, oxygenated perfusion (HOPE) provides cardioprotection by preserving the vasculature through the production of nitric oxide.Methods: Following anaesthesia, diaphragm transection and circulatory arrest in male Wistar rats to simulate DCD conditions, hearts underwent 21 min of warm, in-situ ischemia.Hearts were then subjected to either 30 min of CSS, HOPE, or HOPE with the presence of L-NAME (nitric oxide synthase inhibitor).Afterwards, hearts were reperfused ex-situ for 60 min under oxygenated, normothermic conditions.Results: Compared to CSS, HOPE hearts demonstrated higher cardiac function (determined by cardiac output, left ventricular work, as well as contraction and relaxation rates) after 60 min of reperfusion.Furthermore, preliminary results indicate a higher coronary vascular resistance at the end of the hypothermic perfusion period in hearts with L-NAME compared to HOPE alone.Early reperfusion coronary flow, an indicator of vascular function, tended to be higher in hearts subjected to HOPE compared to hearts treated with L-NAME or to the current clinical scenario (CSS).Conclusion: Preservation of vascular and contractile function with HOPE appears superior to the current clinical protocol (CSS).The increase in coronary flow during early reperfusion in HOPE hearts was abolished with the addition of L-NAME, indicating that the beneficial vascular effects of HOPE could be mediated by the production of nitric oxide.Consequently, we believe that HOPE holds great potential for preservation of cardiac grafts obtained with DCD.

those with advanced heart failure (HF).Racial disparities in disease management also exist.Methods: In a retrospective review of patients referred for advanced HF therapy at our center, evaluation status was classified as approved for evaluation or as terminated due to access to insurance, other or unspecified reasons.Race and gender distributions were compared to statewide proportions adjusted for incidence of HF and by evaluation status.A multivariable model of the proportion approved, accounting for gender, age (<60, 60-69, 70+), race, program (destination VAD, transplant/bridge to transplant VAD), and interactions, was constructed.Results: Of 2893 referred patients, 2085 (72%) were approved for evaluation, 138 (5%) terminated due to insurance access, 108 (4%) other, and 560 (19%) unspecified.Three in 4 referrals were men, indicating a bias relative to statewide data (74% vs. 48%; p<0.001).Moreover, the proportion of men approved was 7% greater than women (95% CI: 3% -11%; Fig. 1A).The racial composition was 25% African American and 73% Caucasian.Relative to statewide data, representation of African Americans was 5% greater (25% vs. 20%; <0.001) and comparable for Caucasians (73% vs. 74%; p = 0.55) with no differences between Caucasians vs. non-Caucasians approved (Fig. 1B).Accounting for variables in Fig. 1C, significant differences in the odds of acceptance were found by gender, race for 60-69 year-olds, and program for 70+ year-olds (Fig. 1D).Conclusion: In this cohort, incoming referral bias toward males was further skewed at entry into the evaluation process for advanced HF therapy.Incoming referral bias toward African Americans is suggested.In 60-69 year-olds, approval for evaluation is skewed toward Caucasians.Understanding this data may help ensure equitable access to advanced HF therapies.

Abstract Background Coronary atherosclerosis is a frequent complication of type 2 diabetes mellitus (DM2). Considering the contiguity with the vascular wall, perivascular adipose tissue (PVAT) could play a crucial role in the pathogenic microenvironment of atherosclerosis. The PVAT attenuation index (p-FAI) is a non-invasive marker that reveals the change in peri-coronary adipose tissue (PCAT). High values of p-FAI are associated with increased cardiovascular mortality and poor prognosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PCAT warrants further investigation in DM2. Purpose We aimed to characterize the association of PCAT by p-FAI and DM2, and to compare coronary inflammation in DM2 versus non DM2 patients with coronary artery disease (CAD), and versus healthy controls. Methods 15 consecutive DM2 patients (9 male, age 63±10 years) without symptoms/signs of cardiovascular disease were included in the study and compared to 8 non DM2 patients with CAD and 13 healthy volunteers without cardiovascular diseases, matched for age and sex. All patients and controls underwent coronary computed tomography angiography (CCTA) for the evaluation of coronary arteries and p-FAI. All scans were performed using a 320-slice multidetector computed tomography (Toshiba Aquilion) and a prospective ECG-triggered sequential acquisition. p-FAI analysis was performed using a dedicated workstation (Aquarius iNtuition Edition version 4.4.13. P3; TeraRecon Inc., Foster City, CA, USA). The proximal 40-mm segment of the right coronary artery (RCA) was identified and the inner and the outer wall were automatically traced, excluding the 10 mm from the ostium. The adipose tissue localized within a radial distance from the outer wall equal to a medium diameter of the RCA was evaluated. Voxel histograms of CT attenuation were traced and included between −190 to −30 HU within the PCAT volume. p-FAI was calculated as the median CT attenuation value of PCAT of the proximal 40-mm segment of the RCA (Figure 1). Results CAD was present in 10 DM2 patients (5 males, aged 63.1±10.5 years); in 5 DM2 patients (4 males, aged 63±11 years) epicardial coronary arteries were normal. p-FAI was higher in DM2 patients than in healthy controls (p=0.004). The presence of CAD did not impact on p-FAI in DM2 patients, presenting a comparable value (p=0.37). p-FAI was higher in DM2 patients with CAD than in non DM2 patients with CAD (p=0.04). Moreover, p-FAI was higher in DM2 patients without CAD than in non DM2 patients with CAD (p=0.002, Figure 2). Finally, p-FAI was not different in non DM2 patients with CAD compared to healthy controls (p=0.65), suggesting the limited role of CAD in the progression of peri-coronary inflammation when compared to DM2. Conclusions Coronary inflammation evaluated by p-FAI measurement was higher in DM2 patients, also without CAD. Therefore, our results suggest that DM2 is a determinant of coronary inflammation stronger than CAD. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

techniques for evaluation of cardiac allograft rejection have been evaluated.In this study, we aim to compare the efficacy of two non-invasive methods of detecting rejection against the gold standard of EMB; gene expression profiling with AlloMap and echocardiographic doppler tissue imaging (DTI).Methods: This was a single-center, retrospective analysis.Electronic medical records of all patients who underwent orthotopic heart transplant at our institution and had at least two concomitant measurements of Allo-Map, echocardiogram DTI and endomyocardial biopsy from January 1 st , 2015 to December 31 st , 2017 were reviewed.Statistical analyses were performed to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value.Rejection for EMB was defined using ISHLT guidelines and was considered present with either acute cellular rejection of 1R or greater or antibody mediated rejection pAMR1 or greater.For non-invasive studies, we considered an AlloMap score of > 34 and a DTI <0.016 m/sec as rejection.Results: A total of 107 patients with available data were reviewed.77% were male.Mean age was 57 years old § 13 years with a range of 22-77 years.AlloMap and DTI performed similarly in our cohort and had NPV of 92% and 88%, respectively when compared to similarly timed EMB.Positive predictive value was 9% for AlloMap and 8% for DTI.Sensitivity was 37% for AlloMap and 18% for DTI and specificity was 65% for AlloMap and 74% for DTI.Conclusion: In our cohort, AlloMap and DTI performed similarly and demonstrated excellent NPV in ruling out rejection.AlloMap has known excellent NPV and has been well-validated for this purpose.The NPV of DTI has been less studied, but performed similarly and is highly cost effective.This could have implications on future screening protocols.This study is limited by the inherent errors of a single-center, retrospective analysis.Further prospective studies to validate this data are ongoing.

term reduction of neoplasia in transplant patients and treating interventionalists.

Vasculitis was present in any grades and types of rejection and is associated with persistence of rejection, CAV development and death. The worse histopathological features is represented by the association of pAMR+ACR and vasculitis.

Abstract Background Coronary microvasculopathy has impact on prognosis in heart transplantation (HT). Distinct contributions by functional or structural alterations of coronary microcirculation in HT and their prognostic role have not been fully elucidated. Purpose We aimed to identify the mechanisms of coronary microvascular impairment in HT and their possible prognostic implications by applying a comprehensive analysis in a comparative study. Methods Included were 134 patients, surviving at least 5 years, with normal systolic function and no evidence of allograft vasculopathy or symptoms/signs of rejection. To permit comparison, 50 healthy volunteers without cardiovascular diseases, and matched for age and sex, served as controls. All underwent echocardiographic evaluation of microvascular function by the assessment of rest and hyperemic diastolic peak blood velocity (DPVr and DPVh). These paired data enable calculation of coronary flow velocity reserve (CFVR) and its inherent companion that is based on the quadratic mean: CFVRC = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated. A CFVR ≤2.5 was considered abnormal; the median value of DPVh (75 cm/s) and CFVRC (80 cm/s) were selected as cut-offs to classify patients. Results HT patients can be assigned to four groups, based on their CFVR and DPVh (Figure A): group 1 (n=32), discordant with preserved CFVR (3.1±0.4); group 2 (n=60), concordant with preserved CFVR (3.4±0.5); group 3 (n=31), concordant with impaired CFVR (1.8±0.3) and group 4 (n=11), discordant with impaired CFVR (2.0±0.2). Group 3 represents the structural microvascular remodeling with high HMR, while group 4 represents the functional remodeling with low BMR. Intriguingly, group 1 showed lower DPVr (p<0.0001) and lower DPVh (p<0.0001) than controls (Figure B, upper panel) with lower CFVR (p<0.0001), even if normal, and lower CFVRC (p<0.0001) than controls (Figure B, lower panel). Moreover, both BMR and HMR were higher in group 1 than in controls (5.3±1 vs 4.4±1.2, p=0.001 and 1.5±0.3 vs 1.1±0.2, p<0.0001, respectively), suggesting structural microvascular remodeling. Conversely, group 2 was comparable with controls (Figure B). Clinical characteristics of the different groups are shown in the Table. 13/32 (40.6%) patients in group 1 died in a follow up of 28 years and mortality rate was comparable to group 3 (14/31, 45.2%). However, CFVRC was <80 cm/s in all 13 deaths in group 1, yet being characterized by preserved CFVR (Figure C). Conclusions A normal CFVR could hide detection of microvascular damage with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (i.e., less rejections and more often diabetes). Being a dimensionless ratio, CFVR may miss some deaths, yet captured by CFVRC. Thus, the combined use of CFVR and CFVRC provides more complete clinical information on coronary microvasculopathy in HT. Funding Acknowledgement Type of funding source: None

Abstract Introduction Right heart catheterization (RHC) is the reference technique for pulmonary capillary wedge pressure (PCWP) measurement but remains invasive. Transthoracic echocardiography (TTE) diastolic parameters (DPs) are used as non-invasive surrogates but have suboptimal accuracy. Left atrial expansion index (LAEI), describing LA reservoir function, could be used for indirectly estimate PCWP. Purpose To evaluate the correlation between LAEI and PCWP and to compare LAEI accuracy against DPs in estimating PCWP. Methods We retrospectively included the patients admitted to our department from 05/2015 to 02/2018 who underwent both a clinically indicated RHC and TTE within 24 hours. PCWP was obtained during RHC. DPs were measured offline and LAEI was calculated from LA maximum volume (MaxVol) and LA minimum volume (MinVol) as LAEI = [(LAMaxVol − LAMinVol) / LAMinVol)] × 100. Results We enrolled 405 patients (left ventricular ejection fraction (LVEF)<50% n=172; PCWP>12mmHg n=209). LAEI showed a logarithmic correlation with PCWP. The log-transformed LAEI (lnLAEI) had an excellent linear correlation (r=−0.82; p<0.001) with PCWP, higher than DPs (LAMaxVoli: r=0.42; E/A: r=0.57; E/e': r=0.51; TRMaxVel r=0.17; all p<0.001). lnLAEI had the highest accuracy in identifying PCWP>12 mmHg (lnLAEI AUC 0.921, p<0.001) when compared to DPs and their association (Figure). lnLAEI showed an independent and added predictive value in estimating PCWP in a model including atrial fibrillation (Afib), heart rate (HR), LVEF, mitral regurgitation (MR), LAMaxVoli, E/A, E/e' and TRMaxVel (Table). Conclusions LAEI is a simple parameter strongly associated with PCWP which might be used for PCWP estimation. Funding Acknowledgement Type of funding source: None

We have demonstrated that there is a decreasing trend of the three types of rejection during the last 6 years of follow up, in particular of cellular rejection. This is not in relation with changing in immunosuppressive drugs, but probably is due to pre and postoperative better management of heart transplant patients.

Coronary microvascular dysfunction (CMD) leads to a worse prognosis in heart transplantation (HT) patients. Coronary flow velocity reserve (CFVR) estimates the physiologic impact of allograft disease on the coronary circulation. Our aim was to determine the prognostic role of CFVR and its companion (CFVRC) on long-term survival of HT patients with a follow-up of 28 years. 134 HT patients, surviving at least 5 years after HT, with normal systolic ventricular function and no evidence of angiographic allograft vasculopathy or symptoms/signs of rejection were included. The enrolled population underwent echocardiographic evaluation of microvascular function by the assessment of both the ratio of hyperemic to rest diastolic peak velocity (DPVh and DPVr). These measurements yield CFVR and its associated companion, defined as CFVRC = √{(DPVr)2 + (DPVh)2}, as well as basal and hyperemic coronary microvascular resistance (BMR and HMR). A CFVR≤2.5 was considered abnormal; the median value of DPVh (75 cm/s) and CFVRC (80 cm/s) were utilized to dichotomize the population. Based on CFVR and DPVh, HT patients can be assigned to four groups: group 1 (n=32), discordant with preserved CFVR (3.1±0.4); group 2 (n=60), concordant with preserved CFVR (3.4±0.5); group 3 (n=31), concordant with impaired CFVR (1.8±0.3) and group 4 (n=11), discordant with impaired CFVR (2.0±0.2). Survival for each patient group is presented in the Figure (panel A). Specifically, survival was similar in group 1 when compared to group 3 (p=0.8), but significantly lower when compared to group 2 (p=0.03). Therefore, a normal CFVR (>2.5) may not be able to predict the unfavourable long-term outcome. CFVR in fact is an incomplete dimensionless ratio; if the paired velocities are low with high BMR and HMR (group 1), the use of CFVR alone may miss some events, that are yet captured by CFVRC. Differences between survivors and no survivors are presented in the Table. At multivariable survival analysis, CMD, DPVh<75 cm/s, CFVRC<80 cm/s were independent predictors of mortality in HT patients. Consequently, we evaluated the added role of the CMD, DPVh<75 cm/s and CFVRC<80 cm/s to prognostic models including the clinical (Figure, panel B) predictors of mortality. The inclusion of CFVRC<80 cm/s to model with clinical predictors of mortality permitted better prediction of survival in HT patients, compared to only adding CMD or DPVh<75 cm/s. This study is the first to demonstrate that the CFVR alone, even representing a determinant of survival in long-term HT patients, is not sufficient to completely predict long-term survival in HT patients. In comparison to CMD and DPVh, the CFVRC provides a significant improvement in survival prediction in long-term HT patients. Thus, the proposed multiparametric approach offers a more comprehensive evaluation of prognosis in HT patients, just by applying available data without the need to perform additional measurements. Type of funding source: None

Background: arrhythmogenic cardiomyopathy (AC) is characterized by fibro-fatty replacement and typically affected the right ventricle (RV), nevertheless the left ventricle (LV) is often involved.Contrast-enhanced cardiac magnetic resonance (CE-CMR) is an optimal technique to investigate biventricular function and tissue characterization abnormalities.LV ventricular-arterial coupling (VAC) is an easily available parameter of LV mechanics.The role of LV mechanics in AC is nowadays unknown.Purpose: to evaluate the LV mechanics and the relationship between LV VAC and fibro-fatty replacement, detected on CE-CMR, in AC patients.Methods: 105 patients with diagnosis of AC, according to 2010 Task Force Criteria, have been retrospectively enrolled in our study from June 2003 to October 2018.All the population underwent a CE-CMR with a dedicated protocol, including biventricular morpho-functional assessment by steady-state free precession sequences and tissue characterization using both T1-weighted fast spin-echo and late postcontrast sequences.A concomitant non-invasive blood pressure measurement was performed.LV VAC was defined as the arterial elastance (EA) to LV end-systolic elastance (EES) ratio and it was defined normal if < 0,65.The study population was divided in coupled and uncoupled groups, according to LV VAC value.LV mechanics in classical and biventricular AC and the extent of LV late gadolinium enhancement (LGE) were compared in coupled and uncoupled patients.Results: the study population was divided in 58 uncoupled (55,2%) and 47 coupled subjects (44,7%).The overall population presented a remarkable alteration of both EES (coupled group 2 mmHg/ml [1,4]; uncoupled group 1,4 mmHg/ml [1,1-1,7]; p < 0,001) and EA (coupled group 1 mmHg/ml [0,9-1,2]; uncoupled group 1,2 mmHg/ml [1,1-1,6]; p = 0,008).In classical AC, uncoupled patients (31%) presented lower value of EA (coupled group 1 mmHg/ml [0,9-1,3]; 1,3 mmHg/ml [1,1-1,8]; p = 0,044) than coupled subjects (69%).In biventricular AC a significative decrease of EES (coupled group 2,1 mmHg/ml [1,7-2,4]; uncoupled group 1,3 mmHg/ml [1,1-1,6]; p < 0,001) and an increase of EA (coupled group 1,1 mmHg/ml [0,9-1,2]; uncoupled group 1,2 mmHg/ml [1-1,6]; p = 0,08) were detected in uncoupled patients (64,4%).The extent of LGE was wider, in term of volume estimated with the Signal Threshold versus Reference Mean > 5 standard deviation technique (coupled group 0,5 grams [0-5,7]; uncoupled group 8,3 grams [2,2-13]; p < 0,001), and in term of segments involved (coupled group 1 [0-3]; uncoupled group 4 [0,75-6]; p < 0,001) in uncoupled subjects.Conclusions: Classical and biventricular AC are characterized by notable LV mechanical alterations, even in patients with preserved LV ejection fraction.Moreover, the extent of fibro-fatty replacement is related to LV uncoupling in AC patients.