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Few data are already available on the follow up of heart transplant (HTx) patients for systemic rare diseases. Aim of the study was to assess the cardiovascular, non-cardiovascular outcome and quality of life (QoL) of heart transplant patients with systemic diseases. We have reviewed all the cases of HTx in rare diseases performed in our Cardiothoracic Department from 1985 to Feb 2021. QoL was assessed by SF-36 questionnaire. Since 1985, out of the 680 HTx performed at our Centre, 25 patients had a systemic rare disease (cardiac amyloidosis, Danon, Becker distrophy, see Fig 1) as cause of advanced heart failure (HF) needing of HTx. Mean age was 45±15 years old, mostly males (76%); 3 patients were in urgent list. The peripheral muscular involvement was present in 11 cases; however, almost all patients retained the capacity of walking. Donors mean age was 37±11 and 16 (64%) were male. Eleven (44%) were considered non-standard donors (ischemic time >4 hours in 5 (20%), cardiac arrest or LVEF<50% or coronary artery disease in 3 (12%), previous drug abuse in 2 (8%). Considering the cardiovascular outcome, the survival was 100% at 30-days, 96% and 90% at 1 and 5 years after HTx in a median follow up of 72 (range 7-318) months. Rejection >2 grade was in 6 (24%), while cardiac allograft vasculopathy in 4 (16%). Related the non-cardiovascular outcome, there was ocular and muscular worsening in 6 (24%) and 9 (36%) cases, while 3 (12%) developed severe psychosis. Lastly, the SF-36 questionnaire showed lower scores for the items related to Physical Component Summary, while similar scores compared to the general population for the Mental Component Summary. In a median follow up of 5 years, HTx patients with systemic rare disease showed a satisfied general survival. The ocular and muscular worsening related to the systemic disease could be very frequent, conditioning the QoL. The relapse of the systemic disease is a rare event, although possible. [ABSTRACT FROM AUTHOR]

Alongside the classical cold storage with ice, other techniques for graft preservation are increasingly used. The purpose of this study is to analyze the results of Heart Transplantation (HTx) in relation to the preservation technique of the graft. Between 2020 and 2022, 55 patients received HTx with grafts preserved with iced-cold storage (CS, n=27), normothermic perfusion with Organ-Care-System (OCS, n=15), and controlled 4°C hypothermia with Paragonix SherpaPak (SP, n=13). The three groups were compared for clinical characteristics, results and iystological graft examinations. Compared to the CS, OCS and SP patients had a higher IMPACT score (p=0.08) and more LVAD support (p=0.01). Extended-criteria donor rate was similar between groups, while ischemic time significantly reduced in OCS (p<0.01). 30-day mortality and PGD≥moderate grade were 1(4%), 2(13%) e 1(7%) (p=0.33) and 1(4%), 3(20%) e 0% (p=0.11) among CS, OCS and SP. Overall and cardiac-related 1-year mortality were 1(4%), 2(13%), 1(7)% (p=0.03) and 0%, 2 (13%), 0% (p=0.21) among groups CS, OCS and SP. After preservation and prior to the implant, grafts preserved with ice were more likely to show edema, while those preserved with normothermic perfusion developped more hemorrhagic lesions. Controlled hypothermia and normothermic perfusion were adopted in increasingly complex and high-risk scenarios with satisfactory results. In relation to the characteristics of donors and recipients, the graft preservation technique could have an impact on the outcomes after HTx [ABSTRACT FROM AUTHOR]

Metabolic Syndrome (MS) is a multifactorial condition that increases the risk of cardio-vascular events, it's frequent in Heart transplant (HTx) candidates and worsens with immunosuppressive therapy. Aim of the study was to analyse the impact of MS on long-term outcome of HTx patients. MS was defined through the presence of at least 3 of the following factors: • -Triglyceride ≥150mg/dl or drug treatment for hypertriglyceridemia • -HDL <40mg/dl for men and <50mg/dl for women • -Blood glucose ≥100mg/dl or diabetes mellitus • -Arterial pressure ≥130/80 or hypertensive drug treatment • -BMI>30 In 349 HTx patients since 2007, mortality and morbidity predictors were evaluated. MS was present in 35% of patients pre-HTx and 47% within the first year of follow-up. Five-year survival in patients with pre-HTx MS was worst (65% vs 78%, p<0.01), as well as in those with MS in the first year of follow-up (78% vs 89%, p<0.01). At the univariate analysis, risk factors for mortality were recipient age (HR 1.07, 1.04-1.09, p<0.01), pre-HTx MS (HR 1.86, 1.29-2.69, p<0.01), pre-HTx hypertension (HR 2.46, 1.70-3.55, p<0.01), pre-HTx hypertriglyceridemia (HR 1.50, 1.04-2.18, p=0.03), chronic renal failure (HR 2.95, 2.03-4.27, p<0.01), MS and diabetes at 1-year follow-up (HR 2.00, 1.25-3.19, p<0.01; HR 2.02, 1.27-3.23, p<0.01, respectively). The last two resulted also risk factors for CAV (HR 1.86, 1.16-2.99, p=0.01; HR 1.67, 1.03-2.69, p=0.04, respectively). MS at 1-year follow-up determined a significant higher risk to develop CAV at 5- and 10-year follow-up (25% vs 14% and 44% vs 25%, p<0.01). MS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) represents a relevant issue after Heart Transplantation (HTx), affecting mid and long-term outcomes. Coronary artery disease (CAD) of the donor graft has been implicated in the pathogenesis and progression of CAV. Although definitive data are still lacking, CAD of the donor graft represents an exclusion criteria in many transplant Units. We analyzed the outcomes of patients who underwent HTx from donor hearts affected by no-severe CAD. Patients who received a graft, evaluated with coronary angiogram before the retrieval, were divided into two groups according to the presence or not of no-severe CAD (with lesions ≤50%) of the donor graft (groups CAD and NCAD, respectively). The outcomes analyzed were survival and freedom from grade ≥2 CAV. The study period was between 1990 and 2018. Median follow up was 86 months (range 0.3-317). There were differences between CAD and NCAD groups according to the baseline characteristics, as reported in Table 1. Survival and Freedom from grade ≥2 CAV were similar between the two groups at mid term (p=0.47 and p=0.66, Figure 1). At adjusted multivariate analysis for both survival and freedom from grade ≥2 CAV, donor CAD was not considered a significant risk factor. Coronary angiogram plays a reliable role in identifying suitable organs, even those affected by CAD. In fact, no-severe donor CAD does not seem to affect survival and development of high grade CAV, more likely due to immunological factors. If confirmed by larger studies, these finding could encourage the employment of donor hearts affected by CAD. [ABSTRACT FROM AUTHOR]

Purpose Heart transplantation (HTx) is the best therapeutic option for patients suffering from end-stage heart failure, but the shortage of donor hearts still represents a crucial problem. Methods Since 1985 to December 2017, a total of 611 HTx in 600 patients have been transplanted at our Centre. The aim of the study is to analyze the short- and long-term results of HTx in patients with older donor age, comparing the < 60 (Group A) vs ≥60 - 64 years old (Group B) vs ≥ 65 - 69 years old (Group C). Results The mean age at HTx was 55±11.1 years. Of these, 561 (91%) received a donor heart <60 years old, while 40 (7%) patients received a donor heart ≥60 - 64 years old (mean donor age 62.7±2.4 years), and 10 patients (2%) received a donor heart ≥ 65 - 69 years old (mean donor age 66.7±2.4 years). Recipients transplanted with donors <60 years were significantly younger compared to the other two Groups (mean age 55 ± 11.1 vs 59 ± 11.1 vs 61.1 ± 12.8 years old, p < 0,01); otherwise, no difference has been reported comparing the Group B vs the Group C (p=0.72). Furthermore, recipients from donors of Group A had more previous cardiac surgery (52% vs 31% vs 29%, p < 0.001); but no difference has been reported comparing the Group B vs the Group C (p=0.49). No differences have been reported in the aetiology of the cardiomyopathy or total ischemia time (194.5±58.8 min vs 187.1 ±62.5 min, p=0.4).Considering the donor < 60 years group, 22 HTx patients (4%) died in the first month after HTx; conversely 7 patients (13%) died early from the Group B and 2 HTx patients (20%) from the Group C. In a mean follow up of 216 ± 48 months, a total of 503 patients (81%) was alive after the first year from the Group A, compared to 38 (76%) from the Group B and 8 (80%) from the Group C. Conclusion In the older donor groups, the incidence mortality is highest in the first month from HTx; conversely, it appears similar at 1-year between donor < 60 and ≥60 years old, even if when ≥65 years old have been considered. It could be reliable to expand the cardiac donor pool by accepting allografts from donors ≥ 60 years of age in selected cases. [ABSTRACT FROM AUTHOR]

Purpose The ex-vivo normothermic perfusion in Heart Transplantation (HTx) allows to expand the donor pool by reducing the ischemic time and providing graft evaluation. Aim of the study was to compare the traditional cold storage (CS) and ex-vivo normothermic perfusion (EVP) in HTx employing marginal donors. Methods Since 2011, 87 HTx employing marginal donors (age>55 years; expected ischemic time>4h; LVEF<50%; IVS>14mm; drug abuse; cardiac arrest; CAD) in standard recipients has been performed, CS was utilized in 70 cases (80%) and EVP in 17 (20%). Pre-operative data, survival and complications at short and long term were analysed. Endomyocardial biopsies were collected at time of organ retrieval (T0), before implantation (T1) and after aortic declamping (T2) for light and electron mycroscopy. Blood samples were collected at T0 and T2 from coronary sinus and peripheral vein for metabolomic evaluation. Results Preoperative data were similar in the two groups. Three organs (15%) were considered not suitable for HTx after EVP. Ischemic time and surgical time were shorter in EVP group, which showed a better short and long term survival: a 5-year survival of 100% vs. 94%, 82% and 73% at 30-day, 1 and 5 years respectively in CS group (p=0.06) and less overall complications (65% vs. 89%, p=0.02). In CS group, endomyocardial biopsies showed a tendency for more prominent myocardial damage after heart reperfusion, especially underlined by mitochondrial and organelles dysfunction (figure1). Conclusion EVP permits to exclude not suitable grafts, to reduce complications and to obtain optimal HTx survival. Pathological findings show a tendency for better myocardial protection. [ABSTRACT FROM AUTHOR]

The distance of recipients residency from the heart transplant (HT) Center could condition the treatment received, and thus long-term results. Aim of the study was to verify the impact of the distance from our Center on long-term outcome after HT. Adult patients receiving HT at our Centre since 1985 were enrolled. Patients supported with ECMO, VAD, high inotropic support or mechanical ventilation at the time of HT were excluded. Patients were divided in two groups according to the distance from our Center: Northern area (NA, ≤200 mi) and Centre-Southern area (CSA, >200 mi). Baseline recipients and donors characteristics are shown in Table 1. During a median follow up of 90 and 82 months (p=0.59) for NA and CSA groups, survival was worse for patients closest to the HT Center, p=0.02 (Fig 1). Compared to CSA group, NA patients were more frequently affected by neoplasia (p=0.03), and less by ≥grade 2 rejection (p=0.03), with no differences among the incidence of infections and CAV. There were no differences in immunosuppressive and other medical therapy at 1,5 and 10 years after HT. However, NA group showed higher median creatinine level at 5-year follow-up (p=0.03) and higher median cholesterol level at both 5 (p<0.01) and 10-year follow-up (p=0.04). The distance of recipient residency from the HT Center seems not to negatively affect the outcome after HT. Indeed other factors, probably related to genetic and lifestyle characteristics, that typically differ in the two Italian areas considered, could have influenced the observed results. Further in-depth prospective studies are required to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Purpose Increasing recipient (RA) and donor age (DA) are independently associated with mortality after Heart Transplantation (HT). The aim of this study was to analyse the impact of age-matching on HT survival. Methods 485 recipients who underwent HT between 1990 and 2018 in our Institution were divided into 4 groups: RA<60-DA<50 (Group 1), RA<60-DA>50 (Group 2), RA>60-DA<50 (Group 3), RA>60-DA>50 (Group 4), and their outcomes were compared. Emergency HT, bridge with MCS and re-HT were excluded. Mean follow-up was 109 ± 84 months. Results Preoperative data reported in Table 1. 30-day mortality across the groups was 4.9%, 9.8%, 8.1%, 9.2% from Group 1 to 4 (p=0,4). The survival of Group 1 was significantly higher than that of other groups (p=0,001), figure 1. The outcome of young recipients receiving older donor grafts did not significantly differ from that of older recipients. At multivariate analysis, donor age (HR 1,02; 95%CI:1,007-1,04) and recipient age (HR 1,05;95%CI:1,02-1,09) correlated with long-term mortality. Conclusion In this study, the use of hearts from older donors did not affect survival of older recipients; conversely, in young recipients it increased the risk of mortality. Older donor organs employment is advisable to expand the donor pool, but donor-recipient age matching should be taken into account to improve long-term outcomes. [ABSTRACT FROM AUTHOR]