Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Obesity and outcomes after left ventricular assist device implantation: insights from the EUROMACS Registry.

OBJECTIVES: The objective was to analyse associations between obesity and outcomes after left ventricular assist device (LVAD) implantation. METHODS: A retrospective analysis of the EUROMACS Registry was performed. Adult patients undergoing primary implantation of a continuous-flow LVAD between 2006 and 2019 were included (Medtronic HeartWare® HVAD®, Abbott HeartMate II®, Abbott HeartMate 3™). Patients were classified into 4 different groups according to body mass index at the time of surgery (body mass index <20 kg/m2: n = 254; 20-24.9 kg/m2: n = 1281; 25-29.9 kg/m2: n = 1238; ≥ 30 kg/m2: n = 691). RESULTS: The study cohort was comprised of 3464 patients. Multivariable Cox proportional cause-specific hazards regression analysis demonstrated that obesity (body mass index ≥30 kg/m2) was independently associated with significantly increased risk of mortality (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 1.36, 95% confidence interval 1.18-1.57, overall P < 0.001). Moreover, obesity was associated with significantly increased risk of infection and driveline infection. The probability to undergo heart transplantation was significantly decreased in obese patients (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 0.59, 95% confidence interval 0.48-0.74, overall P < 0.001). CONCLUSIONS: Obesity at the time of LVAD implantation is associated with significantly higher mortality and increased risk of infection as well as driveline infection. The probability to undergo heart transplantation is significantly decreased. These aspects should be considered when devising a treatment strategy before surgery.

A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy.

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

The European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery: third report.

OBJECTIVES: In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS: Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (<3 vs >3 months). RESULTS: In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER<3 months: 1.44 vs AER>3 months: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. CONCLUSIONS: In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent.

Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry.

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre-HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality-related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).

Perioperative hemoglobin area under the curve is an independent predictor of renal failure after cardiac surgery. Results from a Spanish multicenter retrospective cohort study.

Perioperative anemia is an important risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). Nonetheless, the severity of the anemia and the time in the perioperative period in which the hemoglobin level should be considered as a risk factor is conflicting. The present study introduces the concept of perioperative hemoglobin area under the curve (pHb-AUC) as a surrogate marker of the evolution of perioperative hemoglobin concentration. Through a retrospective analysis of prospectively collected data, we assessed this new variable as a risk factor for the development of acute kidney injury after cardiac surgery in 966 adult patients who underwent cardiac surgery with cardiopulmonary bypass, at twenty-three academic hospitals in Spain. Exclusion criteria were patients on renal replacement therapy, who needed a reoperation because of bleeding and/or with missing perioperative hemoglobin or creatinine values. Using a multivariate regression analysis, we found that a pHb-AUC <19 g/dL was an independent risk factor for CSA-AKI even after adjustment for intraoperative red blood cell transfusion (OR 1.41, p <0.05). It was also associated with mortality (OR 2.48, p <0.01) and prolonged hospital length of stay (4.67 ± 0.99 days, p <0.001).

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study.

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

Association of cystatin C with heart failure with preserved ejection fraction in elderly hypertensive patients: potential role of altered collagen metabolism.

OBJECTIVES: Cystatin C has been shown to be associated with heart failure with preserved ejection fraction (HFPEF). In addition, myocardial fibrosis has been involved in diastolic dysfunction in HFPEF. Therefore, we hypothesized that increased cystatin C levels may be associated with altered collagen metabolism, contributing to diastolic dysfunction in patients with HFPEF. METHODS: One hundred and forty-one elderly hypertensive patients with HFPEF were included. Cardiac morphology and function was assessed by echocardiography. Circulating levels of cystatin C, biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I) and degradation [matrix metalloproteinase-1 (MMP-1) and its inhibitor TIMP-1] and osteopontin were analyzed by ELISA. Twenty elderly sex-matched patients with no identifiable cardiac disease were used as controls. In-vitro studies were performed in human cardiac fibroblasts. RESULTS: Compared with controls, cystatin C was increased (P < 0.001) in patients with HFPEF, even in those with a normal estimated glomerular filtration rate (eGFR; P < 0.05). Cystatin C was directly correlated with the estimated pulmonary capillary wedge pressure (P < 0.01), TIMP-1 and osteopontin (P < 0.001) and inversely correlated with MMP-1:TIMP-1 (P < 0.01), but not with carboxy-terminal propeptide of procollagen type I or MMP-1 in all patients with HFPEF. These associations were independent of eGFR. In vitro, osteopontin (P < 0.01) and TIMP-1 (P < 0.001) increased in the supernatant of cardiac fibroblasts exposed to cystatin C. CONCLUSION: In patients with HFPEF of hypertensive origin, cystatin C is increased and associated with diastolic dysfunction and alterations in collagen metabolism independently of eGFR. An excess of cystatin C might contribute to diastolic dysfunction in HFPEF by facilitating myocardial fibrosis via accumulation of osteopontin and TIMP-1.

Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients.

AIM: To determine the clinical reasons for conversion to everolimus (EVL) and long-term outcomes in heart transplant (HT) recipients. METHODS: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT recipients. RESULTS: Two hundred and twenty-two patients were included (mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity (30%), chronic allograft vasculopathy (20%) and neoplasms (17%). The doses and mean levels of EVL at baseline (conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors (CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d (P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL (P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL (P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min (P < 0.001). There were 37 episodes of acute rejection in 24 patients (11%). The most frequent adverse events were oedemas (12%), infections (9%) and gastrointestinal problems (6%). EVL was suspended in 44 patients (20%). Since the database was closed at the end of the study, no further follow-up data is available. CONCLUSION: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

Prophylactic treatment with coenzyme Q10 in patients undergoing cardiac surgery: could an antioxidant reduce complications? A systematic review and meta-analysis.

Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that could have beneficial effects in patients undergoing cardiac surgery with cardiopulmonary bypass. There is no clear evidence about its clinical effects or a systematic review published yet. We aimed to conduct a systematic review and meta-analysis of the literature to elucidate the role of coenzyme Q10 in preventing complications in patients undergoing cardiac surgery with cardiopulmonary bypass. We searched the PubMed Database using the following keywords: Coenzyme Q10, ubiquinone, ubiquinol, CoQ10, Heart Surgery, Cardiac surgery. Articles were systematically retrieved, selected, assessed and summarized for this review. We performed separate meta-analyses for different outcomes (inotropic drug requirements after surgery, incidence of ventricular arrhythmias and atrial fibrillation, cardiac index 24 h after surgery and hospital stay), estimating pooled odds ratios (ORs) or mean differences of the association of CoQ10 administration with the risk of these outcomes. Eight clinical trials met our inclusion criteria. Patients with CoQ10 treatment were significantly less likely to require inotropic drugs after surgery {OR [95% confidence interval (CI) 0.47 (0.27-0.81)]}, and to develop ventricular arrhythmias after surgery [OR (95% CI) 0.05 (0.01-0.31)]. However, CoQ10 treatment was not associated with Cardiac index 24 h after surgery [mean difference (95% CI) 0.06 (-0.30 to 0.43)], hospital stay (days) [mean difference (95% CI) -0.61 (-4.61 to 3.39)] and incidence of atrial fibrillation [OR (95% CI) 1.06 (0.19-6.04)]. Since none of the clinical trials included in this review report any adverse effects associated to CoQ10 administration, and coenzyme Q10 has been demonstrated to be safe even at much higher doses in other studies, we conclude that CoQ10 should be considered as a prophylactic treatment for preventing complications in patients undergoing cardiac surgery with cardiopulmonary bypass. However, better quality randomized, controlled trials are needed to clarify the role of CoQ10 in patients undergoing cardiac surgery with cardiopulmonary bypass.

Bicaval versus standard technique in orthotopic heart transplant: assessment of atrial performance at magnetic resonance and transthoracic echocardiography.

Despite a more physiological morphology of atrial anastomosis in the bicaval technique with respect to standard biatrial anastomosis in orthotopic heart transplantation (OHT), the impact on the long-term outcome is still not clear. In this retrospective study, we sought to investigate the morphology and function of the atria through magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE). Moreover, we aimed to analyse the accuracy of TTE with respect to MRI. Cox regression analysis of 216 consecutive patients receiving OHT between August 1987 and January 2010 identified only recipient age at the time of transplant to be an independent predictor of mortality (P = 0.048, odds ratio = 1.04). After a mean follow-up of 96.6 ± 77.7 months, 108 patients were alive, of which 35 were found to be eligible for MRI assessment. In this analysis, left and right atrial volumes were found to be significantly larger in the standard group in comparison with the bicaval group (P = 0.001), and no significant difference between the two techniques was observed in left and right atrio-ventricular output. Moreover, a significantly reduced accuracy was observed (CCC < 0.3) when TTE results were compared with MRI assessment in evaluating atrial dimensions. Although left and right atrial volumes are significantly larger in the standard group in comparison with the bicaval group, we concluded that no significant difference in the atrial output and survival between the two techniques could be demonstrated.

Left atrial appendage occlusion by invagination and double suture technique.

Left atrial appendage (LAA) plays a crucial role as a source of atrial thrombus in patients with atrial fibrillation (AF). Thus, the need to close LAA becomes evident in patients with AF who undergo concomitant mitral valve surgery. Unfortunately, it has been reported a high rate of unsuccessful LAA occlusion, regardless of the technique employed.We propose a safe and simple method for LAA occlusion consisting in invagination of the appendage into the left atrium, followed by two sutures (purse string suture around the base of the LAA and a reinforce running suture).

Allograft morphology and function in heart transplant recipients surviving more than 15 years by magnetic resonance imaging and dual-source computed tomography.

OBJECTIVE: Cardiac allograft vasculopathy and late graft failure are the main limiting factors of long-term success of heart transplantation, and little is known about graft function in the long-term survivors. The aim of this study was to assess the ventricular function and the allograft vasculopathy in long-term survivors (>15 years) with the cardiac magnetic resonance imaging (MRI) and dual-source computed tomography (DSCT) coronary angiogram. METHODS: In our database, 34 cardiac recipients have more than 15 years of follow-up and were evaluated for this study; 22 (65%) of them were enrolled. Mean age at transplant was 46 ± 13.5 years, mean donor age was 28.5 ± 10.1 years, and mean graft ischemic time was 189 ± 58 min. Mean follow-up was 18.5 ± 2.4 years (range 15-22). All patients underwent cardiac MRI and DSCT. RESULTS: Mean left ventricular (LV) volumes indexed to the body surface area (BSA) were within normal range: the end-diastolic volume/BSA was 61 ± 16 ml m(-2), end-systolic volume/BSA was 22 ± 15 ml m(-2), stroke volume/BSA was 38 ± 6 ml m(-2), LV mass/BSA: 72 ± 18 g m(-2), and mean ejection fraction (EF) was 0.59 ± 0.08. Two patients (9%) showed a global cardiac hypokinesia and two other patients (9%) showed akinesia of one segment. At DSCT, 41% of patients had a strictly normal coronary angiogram, 41% had wall thickening and 18% presented a least one >60% stenosis. CONCLUSIONS: Cardiac MRI and DSCT coronary angiogram revealed a normal graft function and morphology after more than 15 years of transplantation. However, a certain number of patients have significant cardiac allograft vasculopathy and another consistent group has initial disease. These patients deserve further follow-up and tailoring of the immunosuppressive regimen.

Early and late troponin T determination after elective cardiac surgery. Two different meanings.

AIM: Although Troponins are demonstrated to be better predictors than CK-MB in quantification of myocardial damage, the relation between cut-off values for the diagnosis of perioperative myocardial infarction (PMI) and sample time is still not clear. In the present study we sought to analyse the clinical consequence of an early and late cTnt determinations after elective cardiac surgery. MATERIAL OF STUDY: Data of 117 patients undergone elective open heart surgery between January 2006 and June 2007 were prospectively collected. PMI was detected on the basis of postoperative electrocardiography/echocardiography and hemodynamic state. RESULTS: The in-hospital mortality was 1.7%. Eight patients (6.8%) presented PMI. Receiver-operating characteristic (ROC) analyses showed a cTnt cut-off of 1.22 mg/L (CI 0.94 to 0.99, P = 0.0001, 100% sensitivity and 96% specificity) on arrival to ICU for the diagnosis of PMI. On the second post-operative day the cut-off value was 2.8 mg/L (CI 95% 0.84 to 0.98, P = 0.0001) (sensitivity 66% and specificity 100%). At this time the Pearson's test revealed the best correlation to ICU (P = 0.008) and in-hospital (P = 0.01) length of stay (LOS). DISCUSSION: A better sensibility of cTnt in diagnosis of PMI in the early postoperative period has been demonstrated to be associated to an increasing specificity in the late post-operative period. CONCLUSIONS: PMI must be suspected in patients with a cTnt > 1.22 mg/L. A second later assessment on the 2nd post-operative can exclude false positives and significantly predict the ICU and the in-hospital length of stay.

Giant left atrial thrombus 17 years after orthotopic heart transplantation.

We present the case of a 66-year-old woman who underwent orthotopic heart transplantation 17 years earlier for dilated cardiomyopathy. After 7 years allograft coronary vasculopathy developed requiring coronary artery angioplasty. In year 15 postoperatively she experienced congestive heart failure and she became symptomatic requiring diuretics and digoxin treatment. In year 16 postoperatively a routine coronary computed tomography (CT) angiography study revealed a giant thrombus in the left atrium. The patient had had no thromboembolic-related symptoms. Anticoagulation therapy was introduced and the patient has not presented any thromboembolic-related complication. As the symptoms of cardiac insufficiency worsened we decided to evaluate the patient for re-transplantation.

TachoSil surgical patch versus conventional haemostatic fleece material for control of bleeding in cardiovascular surgery: a randomised controlled trial.

OBJECTIVE: Prolonged bleeding during cardiovascular surgery presents a risk for the patient and increases the time and cost of surgery. TachoSil is a ready-to-use haemostatic agent that consists of an equine collagen patch coated with human fibrinogen and thrombin. This trial evaluated the efficacy and safety (< or =30 days post-surgery) of TachoSil surgical patch compared with standard haemostatic fleece for the control of bleeding in patients undergoing cardiovascular surgery. METHODS: Patients scheduled for elective surgery on the heart, ascending aorta or aortic arch requiring cardiopulmonary bypass were eligible for this open-label multicentre trial. After primary haemostatic measures, patients were randomised to TachoSil or conventional haemostatic fleece if an area of persisting haemorrhage was identified (target area). After the application of trial treatment, haemostasis was evaluated at 3 min (primary endpoint). If haemostasis was not achieved, trial treatment was re-applied and haemostasis assessed at 6 min (secondary endpoint). RESULTS: A total of 120 patients were randomised and 119 received trial treatment (TachoSil, n=59; standard treatment, n=60). Twenty-six percent of patients were female and the mean age was 67 years (range: 23-86 years). Baseline characteristics were similar in both the groups. Bleeding occurred mainly from the aorta (56%), right ventricle (16%) or right atrium (13%), more often from a vessel (68%) than tissue (32%), and was assessed to be arterial in 74% of cases. TachoSil was significantly superior to standard haemostatic fleece in controlling bleeding after insufficient primary haemostasis, with 75% (95% confidence interval (CI): 0.64-0.86) of the TachoSil group achieving haemostasis at 3 min compared with only 33% (95% CI: 0.21-0.45) of the standard treatment group (p<0.0001). This difference persisted at 6 min, with 95% of patients achieving haemostasis in the TachoSil group compared with 72% in the standard treatment group (p=0.0006). Three (5%) TachoSil patients compared with 17 (28%) standard treatment patients failed to achieve haemostasis at 6 min and received rescue treatment. TachoSil was well tolerated with adverse events generally similar in the two treatment groups. CONCLUSIONS: TachoSil was significantly superior to standard haemostatic fleece material in obtaining effective and fast intra-operative haemostasis in cardiovascular surgical procedures. TachoSil was safe and well tolerated.

Morphological and functional evaluation of intrapericardial cyst as a cause of severe right heart failure: dual source computed tomography and magnetic resonance imaging.

A case of an intrapericardial cyst causing heart failure due to right ventricular compression is presented. Characterization of the lesion and its repercussion on right ventricular function by means of state-of-the-art dual source computed tomography (DSCT) and magnetic resonance imaging (MRI) is shown. The diagnosis of intrapericardial cyst was confirmed after surgical excision and biopsy. Usefulness of these noninvasive techniques for the diagnosis of this rare entity is emphasized.

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

BACKGROUND: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. METHODS: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. RESULTS: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. CONCLUSIONS: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.