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Endomyocardial biopsies for rejection monitoring after heart transplantation are generally performed through the right internal jugular vein. We aimed to assess the feasibility and safety of using the left internal jugular vein approach as a valid alternative to a femoral vein for endomyocardial biopsies whenever thrombosis of the right internal jugular vein precludes insertion of a bioptome. We have reviewed our experience with heart transplantation in the last 2 decades to identify patients in whom surveillance endomyocardial biopsy was performed through the left internal jugular vein. We herein describe the step-by-step procedure and report the preliminary results. From May 1, 2000 to January 31, 2024, 561 orthotopic heart transplants have been performed in our unit. In 49 patients (8.7%), the right internal jugular vein access was found to be unsuitable or occluded at eco-Doppler evaluation; in 15 of them (30%) a total of 206 endomyocardial biopsies have been performed, using the left internal jugular vein, without complications. Our experience demonstrates that the left internal jugular vein is a valid alternative approach for endomyocardial biopsies when the right internal jugular vein is not available. This technique is feasible, safe and reproducible and allows adequate rejection monitoring after heart transplantation., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: To compare early and late mortality of acute isolated tricuspid valve infective endocarditis (TVIE) treated with valve repair or replacement., Methods: Patients who were surgically treated for TVIE from 1983 to 2018 were retrieved from the Italian Registry for Surgical Treatment of Valve and Prosthesis Infective Endocarditis. All the patients were followed up by means of phone interview or calling patient referral physicians or cardiologists. Kaplan-Meier method was used to assess late survival and survival free from TVIE recurrence with log-rank test for univariate comparison. The primary end points were early mortality (30 days after surgery) and long-term survival free from TVIE recurrence., Results: A total of 4084 patients were included in the registry. Among them, 149 patients were included in the study. Overall, 77 (51.7%) underwent TV repair and 72 (48.3%) TV replacement. Early mortality was 9% (13 patients). Expected early mortality according to EndoSCORE was 12%. The TV repair showed lower mortality and major complication rate (7% and 16%), compared with TV replacement (11% and 25%), but statistical significance was not reached. Median follow-up was 19.1 years (14.3-23.8). Late deaths were 30 and IE recurrences were 5. No difference in cardiac survival free from IE was found between the two groups after 20 years (80 ± 6% Repair Group vs 59 ± 13% Replacement Group, P = 0.3)., Conclusions: Overall results indicate that once surgically addressed, TVIE has a low recurrence rate and excellent survival, apparently regardless of the type of surgery used to treat it., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

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., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

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., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

: Nonischemic-dilated cardiomyopathy (NIDCM) is an entity that gathers extremely heterogeneous diseases. This awareness, although leading to continuous improvement in survival, has increased the complexity of NIDCM patients' management. Even though the endorsed 'red-flags' approach helps clinicians in pursuing an accurate etiological definition in clinical practice, it is not clear when and how peripheral centers should interact with referral centers with specific expertise in challenging scenarios (e.g. postmyocarditis and genetically determined dilated cardiomyopathy) and with easier access to second-line diagnostic tools and therapies. This position paper will summarize each step in NIDCM management, highlighting the multiple interactions between peripheral and referral centers, from first-line diagnostic workup and therapy to advanced heart failure management and long-term follow-up.

Purpose of Review: To deeply investigate one type of intracellular cardiac storage disease, the Fabry disease and one example of extracellular cardiac storage disease, the cardiac amyloidosis, with the aim to collect data about cardiac treatment at the end-stage level and the feasibility of heart transplantation (HTx) in this setting of patients., Recent Findings: Some registry describes that Fabry disease and cardiac amyloidosis showed similar characteristics as hypertrophic cardiomyopathies; thus, their correct diagnosis is often missing or time consuming. A multiorgan approach is mandatory to recognize the main systemic findings of these diseases, involving also the kidneys, the brain, the autonomous system and the skin., Summary: The early diagnosis of these diseases is required to start as soon as possible the correct therapy for the patients affected. However, the end-stage heart failure is common and HTx could be offered to selected patients, especially if affected by light chain cardiac amyloidosis, to allow to perform the autologous stem cell transplantation after the cardiac transplant. Considering the Fabry disease patients, the enzyme recombinant therapy is also mandatory after HTx to avoid potential release of the systemic disease on the donor graft.

: Heart transplantation is a life-saving therapy for some patients admitted for acute myocarditis. However, controversial exists about the major risk of rejection following heart transplantation in specific types of myocarditis. Because of relatively few data on the post heart transplant outcomes, we report the long-term follow-up of a 39-year-old patient with a previous history of ulcerative colitis, which rapidly worsened heart failure until an emergency heart transplant in 2004.The clinical course was complicated by many episodes of rejection; lastly, after the development of severe cardiac allograft vasculopathy, re-heart transplantation was needed. The main findings of this case are: 1) inflammatory aetiology should always be suspected in patients with concomitant autoimmune disease that developing rapidly progressing heart failure; 2) patients with inflammatory myocardial disease undergoing heart transplantation should also undergo strict immunological surveillance; 3) the option of performing the re-heart transplant in a patient with a so complex management in the first one could be uncertain, but in this case the young age and lack of noncardiac comorbidities were effective to favour the survivor after two immunologically so challenging heart transplantation.

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 ± 4.2 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.

Background: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization., Methods: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint., Results: Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02)., Conclusions: Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy.

Rationale: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities., Objective: Compare the reparative potential of saphenous vein-derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements., Methods and Results: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4., Conclusions: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts., (© 2015 American Heart Association, Inc.)

Background: The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration., Methods and Results: Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P<0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6-85.5] versus 95.4% [95% confidence interval, 83.9-100], P<0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28-3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable., Conclusions: Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.

Introduction: Surgical treatment of Jehovah's witnesses is a special challenge for cardiac surgery. The purpose of this study was to evaluate perioperative management and mid-term clinical outcome of Jehovah's witnesses who underwent cardiac surgery., Methods: Between January 1990 and June 2009, 34 Jehovah's witnesses (22 men, mean age 66 +/- 8 years) underwent cardiac surgery. Surgical procedures included 17 coronary artery bypass grafts (CABG): 3 CABG and aortic valve replacements (AVR); 1 CABG and mitral valve plasty (MVP); 6 AVR; 1 subaortic membrane resection; 2 mitral valve replacements (MVR) and 2 MVP; 1 mitro-aortic valve replacement; and 1 cardiac foreign body removal. There were four urgent operations; 14 patients had NYHA class II-III. Sixteen patients received erythropoietin preoperatively. Preoperative haemoglobin (Hb) value was 14.2 +/- 1.4 g/dl., Results: Extracorporeal circulation time was 127 +/- 66 min, aortic cross-clamping 84 +/- 45 min. Haemoglobin value 24 h after surgery was 11.2 +/- 1.7 g/dl, haematocrit 34.1 +/- 5.2%. None required surgical reoperation for bleeding.Intensive care unit stay was 2.3 +/- 4.3 days, hospital stay 12.3 +/- 10.4 days; there was no hospital mortality. Postoperatively, erythropoietin was administered to 19 patients. Follow-up was completed in 100%. Reoperation was necessary 8 years later in one patient for mitral bioprosthesis degeneration; the patient died 8 months later. All other patients are alive 59 +/- 60 months after surgery; actuarial survival is 100% and 80 +/- 2% at 5 and 10 years, respectively., Conclusion: In our limited experience, early and late surgical results of Jehovah's witnesses patients are satisfactory. Appropriate preoperative management, optimization of Hb values, intraoperative measures to reduce the risk of bleeding and total blood loss recovery are the goals to achieve these results.

Despite the fact that the rate of surgical complications mainly related to the necessary anticoagulation has been reported to be significant in patients supported by ventricular assist devices (VADs) who underwent noncardiac surgery, we report two cases showing that adequate peri-operative management of medical therapy and utilization of mini-invasive surgical approaches (i.e. laparoscopy) may limit the risks of morbidity, especially when surgery is required on an urgent basis.

Background: Pharmacokinetic modeling supports trough monitoring of everolimus, but prospective data comparing this approach versus mycophenolate mofetil (MMF) in de novo cardiac transplant recipients are currently unavailable., Methods: In a 12-month multicenter open-label study, cardiac transplant patients received everolimus (trough level 3-8 ng/mL) with reduced cyclosporine A (CsA) or MMF (3 g/day) with standard CsA, both with corticosteroids+/-induction therapy., Results: In total, 176 patients were randomized (everolimus 92, MMF 84). Mean creatinine clearance was 72.5+/-27.9 and 76.8+/-32.1 mL/min at baseline, 65.4+/-24.7 and 72.2+/-26.2 mL/min at month 6, and 68.7+/-27.7 and 71.8+/-29.8 mL/min at month 12 with everolimus and MMF, respectively. The primary endpoint was not met since calculated CrCl at month 6 posttransplant was 6.9 mL/min lower with everolimus, exceeding the predefined margin of 6 mL/min. However, by month 12 the between-group difference had narrowed versus baseline (3.1 mL/min). All efficacy endpoints were noninferior for everolimus versus MMF. The 12-month incidence of biopsy-proven acute rejection International Heart and Lung Transplantation grade more than or equal to 3A was 21 of 92 (22.8%) with everolimus and 25 of 84 (29.8%) with MMF. Adverse events were consistent with class effects including less-frequent cytomegalovirus infection with everolimus (4 [4.4%]) than MMF (14 [16.9%], P=0.01)., Conclusion: Concentration-controlled everolimus with reduced CsA results in similar renal function and equivalent efficacy compared with MMF with standard CsA at 12 months after cardiac transplantation.

Background: Despite the fact that early and midterm hemodynamic and clinical results of the Cryolife O'Brien (CLOB) stentless valve have been reported to be favorable, the long-term durability and clinical results of this valve are largely unknown. Accordingly, we analyzed 10-year outcomes after aortic valve replacement with this valve., Methods and Results: From January 1994 to September 2004, 185 patients (67, 73, and 75 years, 25th, 50th, and 75th quartiles, respectively; 38% older than 75 years; 56% females) underwent aortic valve replacement with the CLOB valve. Sixty-eight percent of patients were in NYHA class 3 to 4. Standard EuroSCORE was 7.1+/-2.7. Pure aortic stenosis accounted for 42% (n=79), and pure insufficiency for 12% of cases (n=22). Concomitant surgery: 28% coronary artery bypass (n=51), 11% mitral valve replacement/annuloplasty (n=21), and 2% ascending aorta replacement (n=3). Sixty-one percent of patients received a 23-mm valve or smaller size. Follow-up was 100% completed, and cumulative follow-up was 65 months/patient. The 30-day mortality was 5.4% (none were valve related). Actuarial survival at 5 and 10 years were 68% and 40%, respectively. Actuarial freedom from structural valve deterioration was 91% at 5 years and dropped to 44% at 10 years. Actuarial freedom from reoperation was 94% at 5 years and declined to 57% at 10 years., Conclusions: In a population with a high prevalence of elderly females with small aortic root, the CLOB valve demonstrated satisfactory clinical results till 8-years. Afterward, a significant increase in hazard for structural valve deterioration and reoperation occurred in late follow-up.

Background and Aims: Conventional surgery of the thoracic aorta is frequently associated with significant mortality and morbidity. Here we present treatment of surgical pathologies of the thoracic aorta using a less invasive endovascular approach., Methods: From January 2000 to May 2004, 51 patients (mean age 62.7 +/- 12.8 years, 36 men) underwent endovascular repair of thoracic aortic lesions in our institution. All patients underwent computed tomography scan at discharge, 6 and 12 months and annually thereafter. Clinical follow-up was carried out by outpatient clinic visit or by telephone contact with the patients or their referring physicians. Mean follow-up was 15.8 months., Results: The 30-day mortality rate was 3.8%, one death in the group of chronic (1.9%) and one in the group of acute lesion (1.9%). The survival rate in the follow-up period was 92.4% at 6 months. Computed tomography angiography confirmed exclusion of the lesion in 25 out of 27 chronic patients, whereas type I and II endoleaks were detected in two patients treated with a secondary procedure. In addition, two patients with an acute type B aortic dissection presented with early endoleaks. The overall rate of complications was 10%. No other endoleaks or deaths were observed at later follow-up., Conclusions: The early and mid-term results of endovascular stent-grafting for the treatment of chronic and acute thoracic aortic diseases showed a good outcome and low rate of complications. Stent-grafting of the thoracic aorta is still an investigational procedure that needs further validation.

The use of stented bioprostheses in elderly patients with degenerative aortic stenosis, despite being desirable, raises concerns about the harmful effects of residual obstruction to left ventricular outflow. To overcome this limitation new stented and stentless bioprostheses have been designed for supra-annular implant. However, the actual hemodynamic advantage of supra-annular implant over the intra-annular one remains incompletely understood. This review focuses on the geometry of biological valve prostheses designed for supra-annular implant and its implications for the echocardiographic assessment of valve hemodynamics. Available data about the hemodynamic performance of these valves implanted in the supra-annular position in comparison with the usual intra-annular implant are also reviewed. Other issues related to biological heart valve performance, such as biomaterials, tissue mechanics, durability, and clinical outcome are not addressed in this review.

Background: A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients., Methods: Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5+/-3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months., Results: All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P<0.03), 6 (P<0.02), and 12 (P<0.02) months of treatment and at the 12-month follow-up (P<0.02). A complete and sustained response was achieved in all subjects with HBV-related chronic hepatitis, whereas sustained virologic response was observed in one of four HCV patients., Conclusions: The preliminary data emerging from our study indicate that natural leukocyte interferon alfa-N3 can be safely administered in HTx recipients with chronic HBV or HCV viral hepatitis. Further studies with larger numbers of patients are needed to assess the efficacy of interferon alfa-N3 on HCV virologic response.

Thrombotic complications constitute an important risk in transplant recipients, in whom a hypercoagulable state and hypofibrinolysis have been associated with immunosuppressive treatment, especially with cyclosporine. In no case have clotting and fibrinolytic abnormalities been correlated with steroid immunosuppression, even though steroids were always administered. Previous studies found a relationship between hypercorticism and hypofibrinolysis both in Cushing's disease and after renal transplantation. The aim of this investigation was to compare fibrinolytic potential using the venous occlusion test in two similar groups of heart transplant patients treated with or without steroids. Euglobulin lysis time, tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) activities, and antigens were determined before and after the venous occlusion test. A reduced fibrinolytic potential (significant prolongation of lysis time) due to a significant increase in PAI-1 activity and antigen levels was found in heart transplant patients treated with steroids, as compared with patients without steroid treatment and control subjects. The prevalence of reduced fibrinolytic potential was 69.2% (18 cases) in the steroid-treated group and 34.8% (8 cases) in the non-steroid-treated group. In every case, the impaired fibrinolytic potential was due to high basal PAI-1 levels. Our results are compatible with the presence of a hypofibrinolytic state secondary to long-term steroid treatment. In heart transplant recipients, steroid-induced hypofibrinolysis may constitute a further risk factor for thrombotic disease.

Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.