Metabolic Syndrome and Heart Transplantation: An Underestimated Risk Factor?

Metabolic Syndrome (MetS), a multifactorial condition that increases the risk of cardio-vascular events, is frequent in Heart-transplant (HTx) candidates and worsens with immunosuppressive therapy. The aim of the study was to analyze the impact of MetS on long-term outcome of HTx patients. Since 2007, 349 HTx patients were enrolled. MetS was diagnosed if patients met revised NCEP-ATP III criteria before HTx, at 1, 5 and 10 years of follow-up. MetS was present in 35% of patients pre-HTx and 47% at 1 year follow-up. Five-year survival in patients with both pre-HTx (65% vs. 78%, p < 0.01) and 1 year follow-up MetS (78% vs 89%, p < 0.01) was worst. At the univariate analysis, risk factors for mortality were pre-HTx MetS (HR 1.86, p < 0.01), hypertension (HR 2.46, p < 0.01), hypertriglyceridemia (HR 1.50, p=0.03), chronic renal failure (HR 2.95, p < 0.01), MetS and diabetes at 1 year follow-up (HR 2.00, p < 0.01; HR 2.02, p < 0.01, respectively). MetS at 1 year follow-up determined a higher risk to develop Coronary allograft vasculopathy at 5 and 10 year follow-up (25% vs 14% and 44% vs 25%, p < 0.01). MetS 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.

Heart Transplantation in High-Risk Recipients Employing Donor Marginal Grafts Preserved With Ex-Vivo Perfusion.

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13-75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, "out-of-body" time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126-416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2-43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients.

The impact of the distance between patient residency and heart transplant center on outcomes after heart transplantation.

INTRODUCTION: Heart transplant (HTx) recipients require continuous monitoring and care in order to prevent and treat possible complications related to the graft function or to the immunosuppressive treatment promptly. Since heart transplantation centers (HTC) are more experienced in managing HTx recipients than other healthcare facilities, the distance between patient residency and HTC could negatively affect the outcomes. METHODS: Data of patients discharged after receiving HTx between 2000 and 2021, collected into our institutional database, were retrospectively analyzed. The population was divided into three groups: A (n = 180), B (n = 157), and C (n = 134), according to the distance tertiles between patient residency and HTC. The primary end-point was survival, secondary end-points were incidences of complications. RESULTS: Recipient and donor characteristics did not differ between the three groups. Survival at 10 years was 66 ± 4%, 66 ± 4%, and 65 ± 5%, respectively, for groups A, B, and C (p = .34). Immunosuppressive regimen and rate of complications did not differ between groups. However, the rates of outpatient visits and of hospitalization performed at HTC were higher in group A than others. CONCLUSION: Distance from the HTC does not represent a barrier to a successful outcome for HTx recipients, as long as regular and continuous follow-up is provided.

Emerging therapy in light-chain and acquired transthyretin-related amyloidosis: an Italian single-centre experience in heart transplantation.

AIMS: The prognosis for patients affected by light-chain cardiac amyloidosis and acquired transthyretin-related (TTR) amyloidosis is poor. Heart transplantation (HTx) could improve prognosis also enabling autologous stem cell transplantation (ASCT) in the first group. METHODS AND RESULTS: A total of 36 patients affected by systemic amyloidosis have been referred to our centre from 2009 to 2019. Of these, nine had cardiac involvement: seven by light-chain amyloidosis and two by acquired TTR amyloidosis. None died while waiting for HTx. A specific internal protocol useful to select candidates and to monitor the organ involvement after HTx was developed. Median age at diagnosis was 54 years and 66% were male. The most common short-term complication after HTx was renal failure (44%), followed by acute cardiac rejection more than 2R (22%). ASCT was performed in six out of seven light-chain cardiac amyloidosis patients, with a median time of 6 months after HTx. Two patients affected by light-chain cardiac amyloidosis died due to amyloidosis relapse: one before undergoing ASCT. After a median follow-up of 31 (7-124) months, 1- and 5-year survival was 88 and 66% in the cardiac light-chain amyloidosis group. Conversely, 1- and 5-year survival was 100% in the acquired TTR amyloidosis group. CONCLUSION: HTx may represent a valuable option in carefully selected patients. ASCT after HTx is an effective treatment that could decrease amyloidosis relapse in light-chain cardiac amyloidosis patients. A multidisciplinary approach is mandatory to select the best candidates and to obtain the most effective results with a specific surveillance follow-up protocol.

Bentall procedure with the CarboSeal™ and CarboSeal Valsalva™ composite conduits: long-term outcomes.

OBJECTIVES: Data on the long-term results with the standard CarboSeal™ mechanical conduit used for the modified Bentall procedure are lacking as well as information on performance of the Valsalva CarboSeal™ conduit. METHODS: We have analysed 208 recipients of a standard (n = 110) or a Valsalva (n = 98) CarboSeal™ conduit. The median age was 60 years and 90% were males; 35 (17%) had type A aortic dissection and 65 (30%) a bicuspid aortic valve. Data were retrospectively analysed and results were compared between the 2 conduit models. RESULTS: Early mortality was 1.9%; the mean follow-up was 175 ± 95 for standard and 94 ± 51 months for Valsalva conduits (P < 0.01). Actuarial survival was 86 ± 4%, 75 ± 6%, 59 ± 7% and 51 ± 9% at 5, 10, 15 and 20 years, respectively. There were 13 thromboembolic episodes with 3 deaths with an actuarial freedom of 98 ± 1%, 94 ± 2%, 90 ± 3% and 89 ± 4% at 5, 10, 15 and 20 years, respectively. Reoperation on the aortic root was performed in 9 patients for endocarditis (n = 8) and pseudoaneurysm at the right coronary button (n = 1) with an actuarial freedom of 97 ± 1%, 95 ± 2%, 92 ± 3% and 87 ± 4% at 5, 10, 15 and 20 years, respectively. There were no differences between the 2 conduit models in survival and major postoperative complications. CONCLUSIONS: The CarboSeal™ conduit has shown gratifying overall performance up to 20 years and appears a valid option for a modified Bentall operation, when a mechanical prosthesis is indicated. Both CarboSeal™ conduit models provided not statistically different overall long-term results.

Bridge to heart transplantation in patients with cardiogenic shock: a 20-year experience with two different surgical strategies.

AIMS: We aimed to describe how treatment of patients in cardiogenic shock bridged to heart transplantation with mechanical circulatory support, using either biventricular assist devices (BVADs) or extracorporeal life support (ECLS), has evolved in the last 20 years in our centre. METHODS: Since 1998, 72 patients with refractory heart failure and indication for heart transplantation have received mechanical circulatory support: 40 had an ECLS system and 32 a BVAD. RESULTS: Early mortality was similar (17.5 vs. 9.4%, P = 0.25) regardless of the type of support. After a median support time of 8 (1-27) vs. 34 (0-385) days (P < 0.01), 70 vs. 65.6% (P = 0.69) of patients underwent transplantation in the two groups. Prior to transplantation, BVAD patients were more stable with lower need for mechanical ventilation (9 vs. 57%, P < 0.01) and dialysis (0 vs. 38%, P < 0.01). Thirty-day mortality after transplantation was similar (18 vs. 14%, P = 0.53). Patients with extracorporeal support had higher rates of renal (P = 0.02) and respiratory failure (P = 0.03), infections (P = 0.02), atrial fibrillation (P = 0.03) and longer ICU stay (P = 0.01). Late survival was similar, while 5-year freedom from coronary vasculopathy was higher in those with BVAD (P = 0.03). CONCLUSION: Although ECLS provides faster and simpler assistance compared with BVADs, no differences in early and medium-term outcomes in the last 20 years were observed in patients with cardiogenic shock. However, BVADs provided longer duration of support, better multiorgan recovery allowing more adequate graft selection, resulting in a lower rate of posttransplant complications.

Influence of donor-transmitted coronary artery disease on long-term outcomes after heart transplantation - a retrospective study.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is an important cause of late mortality after heart transplantation, which may be influenced by preexisting coronary disease (CAD) in the donor heart. METHODS: The aim of this study was to verify whether CAD in the donor heart had any influence on survival, cardiac-related adverse events (CRAEs), and coronary disease progression after transplantation. Donor coronary angiography performed in 289 hearts showed absence of CAD in 232 (no-CAD group) and moderate (≤50%) stenoses (CAD group) in 57. The 2 groups were compared for survival, freedom from CRAEs, and development of grade ≥ 2 CAV after transplantation. RESULTS: Of 30-day mortality and postoperative complication rate was similar as mean follow-up (76 ± 56 and 75 ± 55 months) for no-CAD and CAD (P = 0.8). Ten-year actuarial survival was 58 ± 4% and 62 ± 7% for no-CAD and CAD (P = 0.4). Ten-year freedom from grade ≥ 2 CAV and from CRAEs was 81 ± 4% and 66 ± 5% vs 75 ± 8% and 67 ± 9% in no-CAD and CAD (P = 0.9 and 0.9, respectively). CONCLUSIONS: Donor hearts with moderate CAD did not affect survival, freedom from CRAEs and did not accelerate development of high-grade CAV after transplantation supporting the use of such grafts to expand the donor pool. Routine use of coronary angiography in donor selection appears justified.

Heart transplant outcomes in patients with mechanical circulatory support: cold storage versus normothermic perfusion organ preservation.

OBJECTIVES: Patients with mechanical circulatory support bridged to a heart transplant (HTx) are at higher risk of postoperative graft dysfunction. In this subset, a mode of graft preservation that shortens graft ischaemia should be beneficial. METHODS: The outcomes of 38 patients on mechanical circulatory support (extracorporeal life support, left ventricular assist device and biventricular assist device) who received a HTx between 2015 and 2020 were analysed according to the method of graft preservation: cold storage (CS) group, 24 (63%) or ex vivo perfusion (EVP) group, 14 (37%). RESULTS: The median age was 57 (range 30-73) vs 64 (35-75) years (P = 0.10); 88% were men (P = 0.28); extracorporeal life support was more frequent in the CS group (54% vs 36%; P = 0.27) versus left ventricular and biventricular assist devices in the EVP group (46% vs 64%; P = 0.27). Clamping time was shorter in the EVP group (P < 0.001) and ischaemic time >4 h was higher in the CS group (P = 0.01). Thirty-day mortality was 13% (0-27%) in the CS group and 0% (P = 0.28) in the EVP group. A significantly lower primary graft failure [7% (0-23%) vs 42% (20-63%); P = 0.03] was observed in the EVP group. Survival at 1 year was 79 ± 8% (63-95%) in the CS group and 84 ± 10% (64-104%) in the EVP group (P = 0.95). CONCLUSIONS: Our results support the use of ex vivo graft perfusion in patients on mechanical circulatory support as a bridge to a HTx. This technique, by shortening graft ischaemic time, seems to improve post-HTx outcomes.

Preservation by cold storage vs ex vivo normothermic perfusion of marginal donor hearts: clinical, histopathologic, and ultrastructural features.

BACKGROUND: The aim of this study was to match clinical outcomes of heart transplantation (HTx) against histopathologic and ultrastructural characteristics of marginal grafts preserved by cold storage (CS) or ex vivo normothermic perfusion. METHODS: Since 2011, 100 patients had undergone HTx at our institution by using marginal donors (aged ≥55 years, expected ischemic time of >4 hours, left ventricular ejection fraction of ≤50%, interventricular septum thickness of ≥14 mm, drug abuse history, episodes of cardiac arrest, and presence of mild coronary artery disease). CS was utilized in 79 cases (Group 1, 79%), and ex vivo perfusion was utilized in 21 (Group 2, 21%). Pre-operative data, survival, and complications in the first 5 years after HTx were analyzed. Myocardial biopsies were collected at graft harvesting, just before implantation, and immediately after aortic declamping. RESULTS: Pre-operative demographics were similar in the 2 groups. Graft utilization rate with ex vivo perfusion was 81%. Ischemic, cardiopulmonary bypass, and surgical times were shorter in Group 2 patients, who showed a lower incidence of overall complications (33% vs 13%, p = 0.04) and better 5-year survival (log-rank, p = 0.04). Moreover, restoration of hypertrophy-related sarcomere changes and mitigation of reperfusion-dependent myocardium injuries were more frequently observed in Group 2 hearts. CONCLUSIONS: Ex vivo perfusion allows for continuous evaluation of marginal donor hearts, favoring exclusion of unsuitable grafts, reduction of complications, and optimal survival of up to 5 years. Such results, supported by consistent histopathologic and ultrastructural findings, suggest better myocardial preservation.

Donor-recipient age interaction and the impact on clinical results after heart transplantation.

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.

Risk scores and surgery for infective endocarditis: in search of a good predictive score.

Objectives: To evaluate scoring systems that have been created to predict the risk of death post-surgery in infective endocarditis (IE). Design: Eight scores - (1) The Society of Thoracic Surgery (STS) risk score for IE, (2) De Feo score, (3) PALSUSE score (prosthetic valve, age ≥70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥10), (4) ANCLA score (anemia, New York Heart Association class IV, critical state, large intracardiac destruction, surgery of thoracic aorta), (5) Risk-Endocarditis Score (RISK-E), (6) score for heart valve or prosthesis IE (EndoSCORE), and (7,8) Association pour l'Étude et la Prévention de l'Endocadite Infectieuse (AEPEI) score I and II - were evaluated in 324 (mean age, 61.8 ± 14.6 years) consecutive patients having IE and undergoing cardiac operation (1999-2018, Regione Autonoma Friuli-Venezia Giulia, Italy). Results: There were 45 (13.9%) in-hospital deaths. Despite many differences on the number and the type of variables, all the investigated scores showed good goodness-of-fit (Hosmer-Lemeshow test, p ≥.28). For five scores, accuracy of prediction (receiver-operating characteristic curve analysis) was good (ANCLA score) or fair (STS risk score for IE, PALSUSE score, AEPEI score I and II). When compared one-to-one (Hanley-McNeil method), accuracy of prediction of ANCLA score was higher than all of other risk scores except for AEPEI score I (p = .077). Conclusions: Five of eight scores that were evaluated in this study showed satisfactory performance in predicting in-hospital mortality following surgery for IE. The ANCLA score should be preferred.

Red blood distribution width and heart transplantation: any predictive role on patient outcome?

BACKGROUND: Red blood cell distribution width (RDW) has been emerging as a strong predictor of mortality among patients with cardiovascular disease. The aim of this study was to verify if RDW is able to predict survival after heart transplantation (HTx). METHODS: Two hundred and eighteen recipients who underwent HTx between 2000 and 2013 were classified into three groups according to the pre-HTx RDW tertile values (14.6 and 16.4%), and their outcomes were compared. Mean follow-up was 6.6 ±â€Š4.2 years. RESULTS: RDW correlated with other markers of chronic pathological conditions, such as the Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score (P = 0.002) and Charlson Comorbidity Index (P < 0.001), and with creatinine levels (P = 0.007), previous cardiac surgery (P < 0.001), diabetes mellitus (P = 0.02), haemoglobin value (P = 0.004), pulmonary capillary wedge and central venous pressures (P = 0.019 and 0.01, respectively), systolic and mean pulmonary artery pressures (P = 0.002 and 0.014, respectively). The rate of 30-day mortality from the lowest to the highest RDW tertile was 1.4, 4 and 9% (P = 0.02), respectively.Long-term mortality correlated at multivariate analysis with recipient age [hazard ratio 1.06, 95% confidence interval (95% CI) 1.02-1.09], donor age (hazard ratio 1.02, 95% CI 1.0-1.04) and RDW (hazard ratio 1.13, 95% CI 1.04-1.23). The survival probability at 4, 8 and 12 years was 90, 84 and 74% for recipients with RDW less than 14.6%, while it was 72, 60 and 42% for recipients with RDW more than 16.4% (hazard ratio 3.29, 95% CI 1.74-6.24). No differences were found between causes of death. CONCLUSION: RDW correlated with survival in HTx recipients. This marker of blood cell size may represent a surrogate of disease and a helpful tool in the risk-assessment process.

Coronary Dissection Discovered During Ex Vivo Organ Preservation: Avoiding a Fatal Complication.

This report describes the case of undiagnosed posttraumatic coronary artery dissection in a young multiorgan donor. Ex vivo preservation with the Organ Care System (TransMedics, Inc, Andover, MA) revealed the presence of coronary disease and avoided transplantation of an organ at high risk for failure.

A Smile Enhances 3-Month-Olds' Recognition of an Individual Face.

Recent studies demonstrated that in adults and children recognition of face identity and facial expression mutually interact (Bate, Haslam, & Hodgson, 2009; Spangler, Schwarzer, Korell, & Maier-Karius, 2010). Here, using a familiarization paradigm, we explored the relation between these processes in early infancy, investigating whether 3-month-old infants' ability to recognize an individual face is affected by the positive (happiness) or neutral emotional expression displayed. Results indicated that infants' face recognition appears enhanced when faces display a happy emotional expression, suggesting the presence of a mutual interaction between face identity and emotion recognition as early as 3 months of age.