Publications by authors named "David Prieto"

42 Publications

Long-Term Clinical and Hemodynamic Outcomes after Heart Transplantation in Patients Pre-Treated with Sildenafil.

Arq Bras Cardiol 2021 02;116(2):219-226

Centro Hospitalar e Universitario de Coimbra EPE, Coimbra - Portugal.

Background: Elevated pulmonary vascular resistance remains a major problem for heart transplant (HT) candidate selection.

Objective: This study sought at assess the effect of pre-HT sildenafil administration in patients with fixed pulmonary hypertension.

Methods: This retrospective, single-center study included 300 consecutive, HT candidates treated between 2003 and 2013, in which 95 patients had fixed PH, and of these, 30 patients were treated with sildenafil and eventually received a transplant, forming Group A. Group B included 205 patients without PH who underwent HT. Pulmonary hemodynamics were evaluated before HT, as well as 1 week after and 1 year after HT. Survival was compared between the groups. In this study, a p value < 0.05 was considered statistically significant.

Results: After treatment with sildenafil but before HT, PVR (-39%) and sPAP (-10%) decreased significantly. sPAP decreased after HT in both groups, but it remained significantly higher in group A vs. group B (40.3 ± 8.0 mmHg vs 36.5 ± 11.5 mmHg, p=0.022). One year after HT, sPAP was 32.4 ± 6.3 mmHg in group A vs 30.5 ± 8.2 mmHg in group B (p=0.274). The survival rate after HT at 30 days (97% in group A versus 96% in group B), at 6 months (87% versus 93%) and at one year (80% vs 91%) were not statistically significant (Log-rank p=0.063). After this first year, the attrition rate was similar among both groups (conditional survival after 1 year, Log-rank p=0.321).

Conclusion: In patients with severe PH pre-treated with sildenafil, early post-operative hemodynamics and prognosis are numerically worse than in patients without PH, but after 1 year, the medium to long-term mortality proved to be similar. (Arq Bras Cardiol. 2021; 116(2):219-226).
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http://dx.doi.org/10.36660/abc.20190047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909968PMC
February 2021

Quadricuspid aortic valve with a hidden left ostium: Case report and literature review.

Rev Port Cardiol (Engl Ed) 2021 Jan 10;40(1):63.e1-63.e5. Epub 2020 Dec 10.

Center of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal.

Quadricuspid aortic valve (QAV) is a rare congenital condition that frequently progresses to aortic regurgitation with clinical impact in adulthood. Surgical treatment is required in the fifth to sixth decade of life in about one fifth of patients. We describe the case of a 64-year-old woman with regular cardiological follow-up for severe aortic valve regurgitation who had suffered recent clinical and echocardiographic deterioration. Conventional open surgery was indicated. During the procedure, a QAV with leaflet retraction and central orifice was observed. The aortic valve was successfully replaced.
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http://dx.doi.org/10.1016/j.repc.2018.04.012DOI Listing
January 2021

Cardiac allograft vasculopathy: Incidence and predictors in a single-center cohort.

Rev Port Cardiol (Engl Ed) 2020 Apr 26;39(4):205-212. Epub 2020 May 26.

Centro Hospitalar da Universidade de Coimbra, Coimbra, Portugal.

Introduction And Aims: Cardiac allograft vasculopathy (CAV) is one of the most significant complications after orthotopic heart transplantation. We aimed to investigate the incidence and predictors of CAV in a large cohort of orthotopic heart transplantation patients.

Methods: We conducted a retrospective analysis on a prospective cohort of 233 patients who underwent transplantation between November 2003 and May 2014. Baseline clinical data and invasive coronary angiograms (n=712) performed as part of the follow-up program were analyzed by two independent investigators.

Results: We included 157 male and 45 female patients with a median age of 66 years. A third of patients had previous ischemic heart disease, 30% peripheral arterial disease, 37% hypertension and 47% dyslipidemia, and 17% were smokers. Acute moderate or severe rejection occurred in 42 patients during the first year. Over a median follow-up of 2920 days, 18% were diagnosed with CAV, with an incidence of 2.91 cases per 100 person-years. Predictors of CAV were previous ischemic heart disease (HR 2.32, 95% CI 1.21-4.45, p=0.01), carotid artery disease (HR 2.44, 95% CI 1.27-4.71, p<0.01), and donor age (HR 1.04, 95% CI 1.00-1.07, p=0.01).

Conclusion: In a single-center cohort of orthotopic heart transplantation patients, predictors of CAV were previous ischemic heart disease, carotid artery disease and donor age.
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http://dx.doi.org/10.1016/j.repc.2019.10.007DOI Listing
April 2020

Improving the odds of drug development success through human genomics: modelling study.

Sci Rep 2019 12 11;9(1):18911. Epub 2019 Dec 11.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Veterans Administration, Boston, MA, USA.

Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them. We estimated the FDR in preclinical science, its effect on drug development success rates, and improvements expected from use of human genomics rather than preclinical studies as the primary source of evidence for drug target identification. Calculations were based on a sample space defined by all human diseases - the 'disease-ome' - represented as columns; and all protein coding genes - 'the protein-coding genome'- represented as rows, producing a matrix of unique gene- (or protein-) disease pairings. We parameterised the space based on 10,000 diseases, 20,000 protein-coding genes, 100 causal genes per disease and 4000 genes encoding druggable targets, examining the effect of varying the parameters and a range of underlying assumptions, on the inferences drawn. We estimated γ, defined mathematical relationships between preclinical FDR and drug development success rates, and estimated improvements in success rates based on human genomics (rather than orthodox preclinical studies). Around one in every 200 protein-disease pairings was estimated to be causal (γ = 0.005) giving an FDR in preclinical research of 92.6%, which likely makes a major contribution to the reported drug development failure rate of 96%. Observed success rate was only slightly greater than expected for a random pick from the sample space. Values for γ back-calculated from reported preclinical and clinical drug development success rates were also close to the a priori estimates. Substituting genome wide (or druggable genome wide) association studies for preclinical studies as the major information source for drug target identification was estimated to reverse the probability of late stage failure because of the more stringent type 1 error rate employed and the ability to interrogate every potential druggable target in the same experiment. Genetic studies conducted at much larger scale, with greater resolution of disease end-points, e.g. by connecting genomics and electronic health record data within healthcare systems has the potential to produce radical improvement in drug development success rate.
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http://dx.doi.org/10.1038/s41598-019-54849-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906499PMC
December 2019

Primary graft failure after cardiac transplantation: prevalence, prognosis and risk factors.

Interact Cardiovasc Thorac Surg 2018 11;27(5):765-772

Centre of Cardiothoracic Surgery, Coimbra Hospital and Universitary Centre, Coimbra, Portugal.

Objectives: Primary graft failure (PGF) is a common and devastating complication, despite the advances in perioperative treatment. We aim to evaluate the prevalence of PGF and its impact on survival and to explore associated risk factors.

Methods: From November 2003 through December 2015, 290 patients submitted to cardiac transplantation were classified into non-PGF (243; 84%) and PGF (47; 16%) groups. The characteristics of the recipients were similar regarding age (54.6 ± 10.6 vs 54.0 ± 9.4 years; P = 0.74), male gender (78.2% vs 72.3%; P = 0.38) and transpulmonary gradient (9.4 ± 4.2 vs 10.5 ± 5.6 mmHg; P = 0.15); donors to the PGF group had similar age (35.5 ± 11.4 vs 37.5 ± 10.7 years; P = 0.27) but were predominantly female (21% vs 42.6%; P = 0.002).

Results: Mean ischaemic (89.0 ± 36.8 vs 103.3 ± 44.7 min; P = 0.019) and cardiopulmonary bypass (92.8 ± 14.5 vs 126.3 ± 62.4 min; P < 0.001) times were longer in the PGF group. Length of hospital stay was 13.5 ± 7.5 vs 28.9 ± 35.2 days (P= 0.005). Hospital mortality was 4.1% [1.6% for non-PGF and 17% for PGF (P < 0.001)]. Survival at 1, 5 and 10 years was 95.5 ± 1.3% vs 55.3 ± 7.3%, 84.1 ± 2.5% vs 47.4 ± 7.6% and 67.1 ± 3.8% vs 14.4 ± 12%, respectively (P < 0.001). Risk factors for PGF were female donor [odds ratio (OR): 2.56; 95% confidence interval (CI): 1.29-5.09; P = 0.007], total ischaemic time (OR: 1.01; 95% CI: 1.00-1.02; P = 0.032) and preoperative mechanical extracorporeal circulatory support (OR: 11.90; 95% CI: 2.62-54.12; P = 0.001).

Conclusions: Our results demonstrate that PGF is associated with poor outcomes that extend beyond the 1st month and the 1st year after heart transplantation. We found female donor, total ischaemic time and preoperative mechanical extracorporeal circulatory support to be risk factors for PGF.
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http://dx.doi.org/10.1093/icvts/ivy151DOI Listing
November 2018

Coronary Allograft Vasculopathy after Cardiac Transplantation: Prevalence, Prognostic and Risk Factors.

Rev Port Cir Cardiotorac Vasc 2017 Jul-Dec;24(3-4):158

Serviço de Cirurgia Cardiotorácica do Centro Hospitalar e Universitário de Coimbra, Portugal.

Introduction: Coronary allograft vasculopathy (CAV) is still a serious long-term complication after cardiac transplantation.

Purpose: To evaluate the prevalence of CAV in a single institution, its impact on survival and to explore associated risk factors.

Methods: From November-2003 through June-2016, 316 patients were submitted to cardiac transplantation. After excluding those with paediatric age (n=8), those with previous renal or hepatic transplantation (n=2) and those who didn't survive the first year after cardiac transplantation (n=40), the study population resulted in 266 patients. Forty two patients (15.8%) with CAV, diagnosed by a new >50% coronary artery stenosis in any vessel during follow-up, were compared with a non-CAV group.

Results: Both groups share de same median age (54+10years). Recipient male sex predominated in the CAV group (93% vs. 74%), as did ischemic etiology (52% vs. 37%). Although not reaching statistical significance, CAV patients also had more dyslipidemia (60% vs. 50%), history of smoking (52% vs. 44%) and peripheral vascular disease (45% vs. 29%). The incidence of celular acute rejection 1R is more frequent in CAV group (69% vs. 60%) such as 2R or 3R (29% vs. 27%). Prolonged use of inotropic support and mechanical assistance after cardiac transplantation were comparable between both groups. The survival of this patients, who were submitted to cardiac transplantation and had lived at least 1 year, between CAV and non-CAV group was comparable at 5-year (91% vs. 85%), but tended to be lower for CAV patients in 10-year interval (52% vs. 73%).

Conclusion: This data confirms CAV as a common long-term complication following cardiac transplantation. Although short to mid-term survival seems not to be affected by CAV, long-term survival appears lower, hence a longer follow-up is needed.
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May 2019

Heart transplantation: Early Results of Two Different Regimes of Immnunosuppression.

Rev Port Cir Cardiotorac Vasc 2017 Jul-Dec;24(3-4):119

CCT-CHUC, Portugal.

Introduction: The management of induction and maintenance immunosuppression therapy after heart transplantation (HT) remains a controversial issue. The dosage and the timing has been a changing target. We aimed at evaluate the incidence of acute cellular rejection (ACR) [≥1R grade], major infection and survival in first year after HT in patients receiving two different induction immunosuppression regimes and with a reduction in intensity of triple maintenance immunosuppression dose.

Methods: From November-2003 to June-2016, 317 patients were submitted to HT. After excluding those with pediatric age (n=8), those with previous renal or hepatic transplantation (n=2), those submitted to retransplantation (n=2), patients with early death without endomiocardial biopsy (n=10) and those in a transition maintenance regime (n=26), the study population resulted in 269 patients. These patients were divided in two groups: patients receiving the previous regime of two doses of basiliximab (group A, n=211) and those receiving a single dose of basiliximab (group B, n=58). All the patients were treated with a maintenance standard triple immunosuppressive regimen of corticosteroids, an inhibitor of calcineurin and mycophenolate mofetil but more immunosuppressive load in group A.

Results: Mean age of the recipients (group A vs. group B) was 54.6±10.6vs.55.0±9.8 years (p=0.808); 77.3%vs.75.9% were male (p=0.861); 28.4%vs.28.1% were diabetic (p=0.957); and ischemic etiology was present in 39.8%vs 41.0% of the patients (p=0.798), respectively. No differences were found, at first year, between the two groups concerning global ACR incidence (55.0%vs.56.9%, p=0.882, respectively) but major ACR (≥2R grade) was slightly superior in group B (16.6%vs.27.6%, p=0.080, respectively). Time-free from major ACR at 3rd, 6th and 12th months was, respectively 91.0±2.0%vs.84.5%±4.8%; 86.7±2.3%vs.74.1±5.7%; and 83.4±2.6%vs.72.4±5.9% (p=0.048). Time-free from major infection at 3rd, 6th and 12th months was, respectively 89.6±2.1%vs.82.8±5.0%; 87.7±2.3%vs.79.3±5.3%; and 84.4±2.5%vs.79.3±5.3% (p=0.253). No differences were found concerning survival at 3rd, 6th and 12th months (94.3±1.6%vs.94.8±2.9%; 92.4±1.8%vs.93.1±3.3%; and 90.0±2.1%vs.91.4±3.7%, (p=0.771) respectively).

Conclusion: With this study, we verified that lowering doses of induction and maintenance therapy was responsible for increase cases of major ACR at first year of heart transplant. However, no differences were found concerning the incidence of major infection and early survival. Hence, effective immunosuppression induction regimen can apparently be done safely with a single dose regime without compromising survival at first year after HT.
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May 2019

Erratum to "Heart transplantation for Chagas cardiomyopathy" (Rev. Port. Cardiol. 2017;36(11):871.e1-871.e4).

Rev Port Cardiol (Engl Ed) 2018 Jan;37(1):95

Coimbra Hospital and University Center, Cardiothoracic Surgery Department, Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.repc.2018.01.002DOI Listing
January 2018

Heart transplantation for Chagas cardiomyopathy.

Rev Port Cardiol 2017 Nov 20;36(11):871.e1-871.e4. Epub 2017 Nov 20.

Coimbra Hospital and University Center, Cardiothoracic Surgery Department, Coimbra, Portugal.

Chagas disease is an endemic disease in Latin America that is increasingly found in non-endemic areas all over the world due to the flow of migrants from Central and South America. We present the case of a Brazilian immigrant in Portugal who underwent orthotopic heart transplantation for end-stage Chagas cardiomyopathy. Immunosuppressive therapy included prednisone, mycophenolate mofetil and tacrolimus. Twelve months after the procedure she is asymptomatic, with good graft function, and with no evidence of complications such as graft rejection, opportunistic infections, neoplasms or reactivation of Trypanosoma cruzi infection. By reporting the first case in Portugal of heart transplantation for Chagas cardiomyopathy, we aim to increase awareness of Chagas disease as an emerging global problem and of Chagas cardiomyopathy as a serious complication for which heart transplantation is a valuable therapeutic option.
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http://dx.doi.org/10.1016/j.repc.2016.08.015DOI Listing
November 2017

Model-based performance and energy analyses of reverse osmosis to reuse wastewater in a PVC production site.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2017 Nov 14;52(13):1218-1225. Epub 2017 Sep 14.

d Solvay, Research and Innovation, Environment Lab , Brussels , Belgium.

A pilot-scale reverse osmosis (RO) followed behind a membrane bioreactor (MBR) was developed for the desalination to reuse wastewater in a PVC production site. The solution-diffusion-film model (SDFM) based on the solution-diffusion model (SDM) and the film theory was proposed to describe rejections of electrolyte mixtures in the MBR effluent which consists of dominant ions (Na and Cl) and several trace ions (Ca, Mg, K and SO). The universal global optimisation method was used to estimate the ion permeability coefficients (B) and mass transfer coefficients (K) in SDFM. Then, the membrane performance was evaluated based on the estimated parameters which demonstrated that the theoretical simulations were in line with the experimental results for the dominant ions. Moreover, an energy analysis model with the consideration of limitation imposed by the thermodynamic restriction was proposed to analyse the specific energy consumption of the pilot-scale RO system in various scenarios.
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http://dx.doi.org/10.1080/10934529.2017.1356194DOI Listing
November 2017

Assessing demineralization treatments for PVC effluent reuse in the resin polymerization step.

Environ Sci Pollut Res Int 2017 Jul 29;24(20):16631-16638. Epub 2017 May 29.

Departamento de Ingeniería Química, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.

To reduce fresh water consumption in a polyvinyl chloride (PVC) plant, the effluent from a biological treatment must be demineralized to be re-used in the resin polymerization process. Demineralization is a critical process, since the quality and the stability of the PVC resins are highly influenced by the water quality used in the process. The main target values for water parameters are the following: conductivity <10 μScm, TOC < 10 mg L, and Al < 0.1 mg L. To achieve this quality, several reverse osmosis membranes from different materials and suppliers were tested and compared in the demineralization treatment. Polyamide membranes showed higher salt rejection compared to cellulose acetate membranes yielding both types similar flux and permeability. Two-pass reverse osmosis treatment was necessary to reach conductivities lower than 10 μS cm. On the other hand, a good quality effluent for reuse was obtained by combining RO and ionic exchange resins. Results showed that good quality PVC resins in terms of color, granulometry, porosity, and bulk density were obtained when demineralized water from two-pass reverse osmosis was used as fresh water, proving the feasibility of the effluent reuse in the PVC industry.
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http://dx.doi.org/10.1007/s11356-017-9217-9DOI Listing
July 2017

Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms.

Trials 2017 01 31;18(1):48. Epub 2017 Jan 31.

Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Background: The CRASH-2 trial showed that tranexamic acid (TXA) administration reduces mortality in bleeding trauma patients. However, the effect appeared to depend on how soon after injury TXA treatment was started. Treatment within 3 h reduced bleeding deaths whereas treatment after 3 h increased the risk. We examine how patient characteristics vary by time to treatment and explore whether any such variations explain the time-dependent treatment effect.

Methods: Exploratory analysis were carried out, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo-controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examine how patient characteristics (age, type of injury, presence or absence of head injury, Glasgow coma scale (GCS), systolic blood pressure and capillary refill time) vary with time to treatment and use univariable (restriction) and multivariable methods to examine whether any such variations explain the time-dependent effect of TXA. If not explained by differences in patient characteristics, we planned to conduct separate prespecified subgroup analyses for the early benefit and late harm.

Results: There was no substantial variation in age or capillary refill by time to treatment. However, the proportion of patients with blunt trauma, the proportion with head injury and mean systolic blood pressure increased as time to treatment increased. Mean GCS decreased as time to treatment increased. Analyses restricted to patients with blunt trauma, those without head injury and those with a systolic blood pressure <100 mmHg showed that these characteristics did not explain the time-dependent treatment effect. In a multivariable analysis the interaction with time to treatment remained highly significant (p < 0.0001). Separate subgroup analyses that examine how the benefits of early TXA treatment and the harms of late TXA treatment vary by systolic blood pressure (≤75, 76-89, >89 mmHg); GCS (severe 3-8, moderate 9-12, mild 13-15); and type of injury (penetrating versus blunt) showed no significant heterogeneity.

Conclusions: The time-dependent effect of TXA in bleeding trauma patients is not explained by the type of injury, the presence or absence of head injury or systolic blood pressure. When given within 3 h of injury, TXA reduces death due to bleeding regardless of type of injury, GCS or blood pressure.

Trial Registration: ClinicalTrials.gov, NCT00375258 . Registered on 11 September 2006.
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http://dx.doi.org/10.1186/s13063-016-1750-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282847PMC
January 2017

Coronary artery bypass surgery without cardioplegia: hospital results in 8515 patients†.

Eur J Cardiothorac Surg 2016 Mar 23;49(3):918-25. Epub 2015 May 23.

Centre of Cardiothoracic Surgery, University Hospital and Faculty of Medicine of Coimbra, Coimbra, Portugal

Objectives: Cardioplegic myocardial protection is used in most cardiac surgical procedures. However, other alternatives have proved useful. We analysed the perioperative results in a large series of patients undergoing coronary artery bypass (CABG) using cardiopulmonary bypass (CPB) and non-cardioplegic methods.

Methods: From January 1992 to October 2013, 8515 consecutive patients underwent isolated CABG with CPB without cardioplegia, under hypothermic ventricular fibrillation and/or an empty beating heart. The mean age was 61.9 ± 9.5 years, 12.4% were women, 26.3% diabetic, 64% hypertensive; and 9.6% had peripheral vascular disease, 7.8% cerebrovascular disease and 54.3% previous acute myocardial infarction (AMI). One-third of patients were in Canadian Cardiovascular Society Class III/IV. Three-vessel disease was present in 76.5% of the cases and 10.9% had moderate/severe left ventricle (LV) dysfunction (ejection fraction <40%). A multivariate analysis was made of risk factors associated to in-hospital mortality and three major morbidity complications [cerebrovascular accident, mediastinitis and acute kidney injury (AKI)], as well as for prolonged hospital stay.

Results: The mean CPB time was 58.2 ± 20.7 min. The mean number of grafts per patient was 2.7 ± 0.8 (arterial: 1.2 ± 0.5). The left internal thoracic artery (ITA) was used in 99.4% of patients and both ITAs in 23.1%. The in-hospital mortality rate was 0.7% (61 patients), inotropic support was required in 6.6% and mechanical support in 0.8, and 2.0% were re-explored for bleeding and 1.3% for sternal complications (mediastinitis, 0.8%). AKI, the majority transient, occurred in 1595 patients (18.9%). The incidence rates of stroke/transient ischemic attack (TIA) and acute myocardial infarction (AMI) were 2.6 and 2.5%, respectively, and atrial fibrillation/flutter occurred in 22.6% of cases. Age, LV dysfunction, non-elective surgery, previous cardiac surgery, peripheral vascular disease and CPB time were independent risk factors for mortality and major morbidity. The mean hospital stay was 7.2 ± 5.7 days.

Conclusions: Isolated CABG with CPB using non-cardioplegic methods proved very safe, with low mortality and morbidity. These methods are simple and expeditious and remain as very useful alternative techniques of myocardial preservation.
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http://dx.doi.org/10.1093/ejcts/ezv177DOI Listing
March 2016

A decade of cardiac transplantation in Coimbra: the value of experience.

Rev Port Cardiol 2014 Nov 12;33(11):671-81. Epub 2014 Nov 12.

Centro de Cirurgia Cardiotorácica e Transplantação de Órgãos Torácicos, Centro Hospitalar e Universitário e Faculdade de Medicina de Coimbra, Coimbra, Portugal. Electronic address:

Introduction And Objectives: To analyze the experience gained in 10 years of the heart transplantation program of the University Hospital of Coimbra.

Methods: Between November 2003 and December 2013, 258 patients with a mean age of 53.0±12.7 years (3-72 years) and predominantly male (78%) were transplanted. Over a third of patients had ischemic (37.2%) and 36.4% idiopathic cardiomyopathy. The mean age of donors was 34.4±1.3 years and 195 were male (76%), with gender difference between donor and recipient in 32% of cases and ABO disparity (non-identical groups but compatible) in 18%. Harvest was distant in 59% of cases. In all cases total heart transplantation with bicaval anastomoses, modified at this center, was used. Mean ischemia time was 89.7±35.4 minutes. All patients received induction therapy.

Results: Early mortality was 4.7% (12 patients) from graft failure and stroke in five patients each, and hyperacute rejection in two. Thirteen patients (5%) required prolonged ventilation, 25 (11.8%) required inotropic support for more than 48 hours, and seven required pacemaker implantation. Mean hospital stay was 15.8±15.3 days (median 12 days). Ninety percent of patients were maintained on triple immunosuppressive therapy including cyclosporine, the remainder receiving tacrolimus. In 23 patients it was necessary to change the immunosuppression protocol due to renal and/or neoplastic complications and humoral rejection. All but two patients have been followed in the Surgical Center. Fifty patients (19.4%) subsequently died from infection (18), cancer (10), vascular (eight), neuropsychiatric (four), cardiac (two) or other causes (eight). Forty-six patients (17.8%) had episodes of cellular rejection (>2 R on the ISHLT classification), eight had humoral rejection (3.1%), and 22 have evidence of graft vascular disease (8.5%). Actuarial survival at 1, 5, and 8 years was 87±2%, 78±3% and 69±4%, respectively.

Conclusion: This 10-year series yielded results equivalent or superior to those of centers with wider and longer experience, and have progressively improved following the introduction of changes prompted by experience. This program has made it possible to raise and maintain the rate of heart transplantation to values above the European average.
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http://dx.doi.org/10.1016/j.repc.2014.03.010DOI Listing
November 2014

Heart Transplantation in Patients Older than 65 Years: Worthwhile or Wastage of Organs?

Thorac Cardiovasc Surg 2015 Dec 21;63(8):684-91. Epub 2014 Nov 21.

Department of Cardiothoracic Surgery and Transplantation of Thoracic Organs, University Hospital and Faculty of Medicine Coimbra, Portugal.

Background: Patients older than 65 years have traditionally not been considered candidates for heart transplantation. However, recent studies have shown similar survival. We evaluated immediate and medium-term results in patients older than 65 years compared with younger patients.

Methods: From November 2003 to December 2013, 258 patients underwent transplantation. Children and patients with other organ transplantations were excluded from this study. Recipients were divided into two groups: 45 patients (18%) aged 65 years and older (Group A) and 203 patients (81%) younger than 65 years (Group B).

Results: Patients differed in age (67.0 ± 2.2 vs. 51.5 ± 9.7 years), but gender (male 77.8 vs. 77.3%; p = 0.949) was similar. Patients in Group A had more cardiovascular risk factors and ischemic cardiomyopathy (60 vs. 33.5%; p < 0.001). Donors to Group A were older (38.5 ± 11.3 vs. 34.0 ± 11.0 years; p = 0.014). Hospital mortality was 0 vs. 5.9% (p = 0.095) and 1- and 5-year survival were 88.8 ± 4.7 versus 86.8 ± 2.4% and 81.5 ± 5.9 versus 77.2 ± 3.2%, respectively. Mean follow-up was 3.8 ± 2.7 versus 4.5 ± 3.1 years. Incidence of cellular/humoral rejection was similar, but incidence of cardiac allograft vasculopathy was higher (15.6 vs. 7.4%; p = 0.081). Incidence of diabetes de novo was similar (p = 0.632), but older patients had more serious infections in the 1st year (p = 0.018).

Conclusion: Heart transplantation in selected older patients can be performed with survival similar to younger patients, hence should not be restricted arbitrarily. Incidence of infections, graft vascular disease, and malignancies can be reduced with a more personalized approach to immunosuppression. Allocation of donors to these patients does not appear to reduce the possibility of transplanting younger patients.
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http://dx.doi.org/10.1055/s-0034-1393959DOI Listing
December 2015

Results of heart transplantation in the urgent recipient--who should be transplanted?

Rev Bras Cir Cardiovasc 2014 Jul-Sep;29(3):379-87

Cardiothoracic Surgery University Hospital, Coimbra, Portugal.

Objective: To evaluate immediate and long-term results of cardiac transplantation at two different levels of urgency.

Methods: From November 2003 to December 2012, 228 patients underwent cardiac transplantation. Children and patients in cardiogenic shock were excluded from the study. From the final group (n=212), 58 patients (27%) were hospitalized under inotropic support (Group A), while 154 (73%) were awaiting transplantation at home (Group B). Patients in Group A were younger (52.0±11.3 vs. 55.2±10.4 years, P=0.050) and had shorter waiting times (29.4±43.8 vs. 48.8±45.2 days; P=0.006). No difference was found for sex or other comorbidities. Haemoglobin was lower and creatinine higher in Group A. The characteristics of the donors were similar. Follow-up was 4.5±2.7 years.

Results: No differences were found in time of ischemia (89.1±37.0 vs. 91.5±34.5 min, P=0.660) or inotropic support (13.8% vs. 11.0%, P=0.579), neither in the incidence of cellular or humoral rejection and of cardiac allograft vasculopathy. De novo diabetes de novo in the first year was slightly higher in Group A (15.5% vs. 11.7%, P=0.456), and these patients were at increased risk of serious infection (22.4% vs. 12.3%, P=0.068). Hospital mortality was similar (3.4% vs. 4.5%, P=0.724), as well as long-term survival (7.8±0.5 vs. 7.4±0.3 years).

Conclusions: The results obtained in patients hospitalized under inotropic support were similar to those of patients awaiting transplantation at home. Allocation of donors to the first group does not seem to compromise the benefit of transplantation. These results may not be extensible to more critical patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412329PMC
http://dx.doi.org/10.5935/1678-9741.20140072DOI Listing
May 2015

Gender mismatch between donor and recipient is a factor of morbidity but does not condition survival after cardiac transplantation.

Transpl Int 2014 Dec 29;27(12):1303-10. Epub 2014 Sep 29.

Center of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal.

We intended to evaluate the influence of sex mismatch between donor and recipient, which is still under much debate, on survival and comorbidities after cardiac transplantation. From November 2003 to December 2013, a total of 258 patients were transplanted in our center. From these, 200 receptors were male (77.5%) and constituted our study population, further divided into those who received the heart from a female donor (Group A) - 44 patients (22%) and those who received it from a male donor (Group B) - 156 (78%). Median follow-up was 4.2 ± 3.0 years (1-10 years). The two groups were quite comparable with each other, except for body mass index, systolic pulmonary artery pressure, and transpulmonary gradient, which were significantly lower in Group A. A low donor/recipient weigh ratio (<0.8) was avoided whenever possible. Hospital mortality was not different in the two groups. During follow-up, global survival was similar, as was survival free from acute cellular rejection and cardiac allograft vasculopathy. However, patients in Group A had decreased survival free from serious infections and malignant tumors. Allocation of female donors to male receptors can be done safely, at least in receptors without pulmonary hypertension and when an adequate donor/recipient weigh ratio is ensured.
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http://dx.doi.org/10.1111/tri.12432DOI Listing
December 2014

Outcome after heart transplantation from older donor age: expanding the donor pool.

Eur J Cardiothorac Surg 2015 Apr 9;47(4):672-8. Epub 2014 Jul 9.

Center of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal

Objectives: There has been a progressive expansion of heart donor selection criteria, including higher age limit. We analysed the impact of using hearts from older age donors (>50 years).

Methods: Between November 2003 and December 2012, 228 heart transplantations were performed. Children and patients requiring ventricular assistance prior to transplantation were excluded. Recipients from 26 donors aged ≥ 50 years (Group A) were compared with those of 136 donors <40 years (Group B). Patient and donor criteria were identical in both groups.

Results: Group A recipients were older than those in Group B (59 ± 11 vs 53 ± 11; P < 0.01), and tended to have more ischaemic cardiomyopathy (50 vs 35%; P = 0.16), be in intensive care (31 vs 27%; P = 0.65) and have longer waiting time (56 ± 49 vs 41 ± 47 days; P = 0.15). There were also significant differences in ischaemic time (65 ± 27 vs 93 ± 35 min; P < 0.01). Thirty-day mortality was similar (3.8 vs 3.7%; P = 0.97). Follow-up was 55 ± 32 months. Actuarial survival at 1, 3 and 5 years was 84 ± 7% for Group A and 90 ± 3, 86 ± 3 and 81 ± 4%, respectively, for Group B (P = 0.85). There were no survival differences between patients younger and older than 60 years, but there was a tendency for decreased survival free from cardiac allograft vasculopathy (CAV) in Group A compared to Group B (at 8 years 65 ± 18 vs 78 ± 7%; P = 0.06).

Conclusions: Parameters of exclusion of donor hearts can and must be adjusted, since the use of selected marginal donors associated with short ischaemic times appears to have no negative impact on morbidity and mortality, more importantly when compared with mortality on the waiting list.
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http://dx.doi.org/10.1093/ejcts/ezu257DOI Listing
April 2015

Central and statistical data monitoring in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial.

Clin Trials 2014 06;11(3):336-343

a Clinical Trials Unit, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.

Background The purpose of monitoring in clinical trials is to ensure the rights, safety, and well-being of trial patients and the accuracy of the trial data. In the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial, which recruited over 20,000 adult trauma patients worldwide, the nature and extent of monitoring was based on a risk assessment undertaken before recruitment started. Purpose We report the methods used for central and statistical monitoring in the CRASH-2 trial and explain how central monitoring was used to target on-site investigations. Methods To ensure that trial participants met the inclusion criteria, we monitored event rates for the primary (death) and secondary outcomes (blood transfusion given). We monitored four quantitative variables (systolic blood pressure (SBP), heart rate (HR), respiratory rate, and capillary refill time) as indicators of the severity of bleeding. We used the coefficient of variation (CV) to identify sites with too much or too little variability. To ensure the accuracy of the data on side effects, we monitored thromboembolic events at each site. Sites with higher or lower than expected event rates were identified for further evaluation. Results A total of 274 sites recruited patients: 145 sites recruited ≥20; patients, and 52 sites recruited ≥100 patients. Sites with low case fatality and low blood transfusion rates were found to be including patients with relatively mild haemorrhage. One site with a high rate of thromboembolic events was found to be using clinical judgement alone. Measurements of SBP and HR varied by about one-fifth of their average value, and capillary refill time measurements varied by around one-third of their average; between-site variation was lowest for blood pressure. Limitations A comparison of mean and median CV indicated that the distributions are slightly skewed to the right. Our simple approach to calculating 95% confidence intervals for the CV may be improved by using a logarithmic transformation of CV for each variable. Conclusions Central and statistical monitoring of data can be used to monitor clinical trials, particularly large, pragmatic, international trials where 100% on-site monitoring is neither necessary nor cost-effective. In the CRASH-2 trial, re-education about trial protocol and the development of guidance helped resolve the issues identified during monitoring.
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http://dx.doi.org/10.1177/1740774513514145DOI Listing
June 2014

Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals.

Int J Epidemiol 2013 Apr;42(2):475-92

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Background: At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.

Methods: We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60,883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).

Results: The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.

Conclusions: In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
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http://dx.doi.org/10.1093/ije/dyt034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619955PMC
April 2013

An unusual cause of acute cardiogenic shock in the operating room.

Echocardiography 2013 Mar 11;30(3):E75-7. Epub 2013 Jan 11.

Department of Cardiology, Coimbra University Hospital, Coimbra, Portugal.

A 51-year-old man with a renal carcinoma with inferior vena cava (IVC) invasion was referred to our hospital for the performance of a radical nephrectomy with IVC thrombus excision. To prevent embolism, an IVC filter was implanted the day before surgery below the suprahepatic veins. On nephrectomy completion, the clinical status of the patient started to deteriorate and an unsuccessful attempt was made to excise the IVC thrombus. The patient developed profound refractory hypotension without significant bleeding and worsening splanchnic stasis was noted. A transesophageal echocardiogram was immediately performed in the operating room, revealing a hemispheric mass protruding from the IVC ostium to the right atrium, completely blocking all venous return. Volume depletion was evident by low left and right atrial volumes and increased septum mobility. No other abnormalities were found that could explain the shock, namely ventricular dysfunction or valvular disease. Cardiac surgery consultation was immediately obtained, ultimately deciding to perform a median sternotomy with direct exploration of right atrium. Under cardiopulmonary bypass, a 6-cm long thrombotic mass was identified, involving the IVC filter, blocking all lower body venous return; the removal of the mass reversed the shock. The patient had an uneventful recovery. Adverse outcomes associated with IVC filters are common. Our case highlights the importance of a team approach to rapid changes in hemodynamic status in the operating room, including the surgeon, the anesthesiologist, and the cardiologist. It also emphasizes the pivotal role of transesophageal echocardiogram in the clinical evaluation of severely unstable patients.
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http://dx.doi.org/10.1111/echo.12094DOI Listing
March 2013

Coronary artery bypass graft surgery during heart transplantation.

Interact Cardiovasc Thorac Surg 2013 Feb 30;16(2):224-5. Epub 2012 Oct 30.

Faculty of Medicine, Centre of Cardiothoracic Surgery, University Hospital, Coimbra, Portugal.

We report the case of a patient who was submitted to coronary artery bypass graft surgery (CABG) during heart transplant as, during bench exploration, the donor heart presented a palpable atherosclerotic lesion in the anterior descending artery, not detected before harvesting. The patent internal thoracic artery from a previous CABG was used.
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http://dx.doi.org/10.1093/icvts/ivs432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548522PMC
February 2013

Diabetes as an outcome predictor after heart transplantation.

Interact Cardiovasc Thorac Surg 2011 Nov 11;13(5):499-504; discussion 504. Epub 2011 Aug 11.

Department of Cardiothoracic Surgery and Thoracic Organ Transplantation, University Hospitals and Faculty of Medicine, Coimbra, Portugal.

We aimed to compare post-transplantation morbidity and survival among heart transplant recipients with and without diabetes mellitus. A retrospective review of 141 adult patients submitted to heart transplantation from November 2003 to June 2009 (with a minimum follow-up of one year) was undertaken. The patients were divided into two groups: those with (29%) and those without (71%) pre-transplantation diabetes. Those with diabetes were older (57.6 ± 6.1 vs. 52.3 ± 11.1 years; P=0.020) and had lower creatinine clearance (53.6 ± 15.1 vs. 63.7 ± 22.1; P=0.029). Nine patients died in hospital (6.4%; P=non-significant). No significant differences in lipid profiles (diabetes vs. no diabetes) existed before transplantation or at one year afterwards. Patients with diabetes showed a significant deterioration in their one-year lipid profile (158 ± 43 vs.192 ± 38 mg/dl; P=0.001), although one-year fasting diabetic was lower than before (178 ± 80 vs. 138 ± 45 mg/dl; P=0.016). During the first year, 17 (17%) patients previously free of diabetes developed new-onset diabetes. No significant differences were seen in rejection at one year (14% vs. 20%), infection (31% vs. 33%), new-onset renal dysfunction (8% vs. 14%) or mortality (17% vs. 7%). One-year survival was not significantly different (83% vs. 94%), but there was a significant decrease in the survival of individuals with diabetes at three years (73% vs. 91%; P=0.020). No significant difference was found in one-year survival or in terms of higher morbidity in the heart transplant patients with diabetes, but a longer follow-up showed a significant decrease in survival. Nonetheless, the patients with diabetes benefited significantly from transplantation and should not be excluded from it.
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http://dx.doi.org/10.1510/icvts.2010.256321DOI Listing
November 2011

Cardiac transplantation: five years' activity.

Rev Port Cardiol 2010 May;29(5):731-48

Programa de Transplantação Cardíaca, Centro de Cirurgia Cardiotorácica, Hospitais da Universidade Coimbra, Coimbra, Portugal.

Objective: To analyze the initial five years experience of the new heart transplant program of Coimbra University Hospitals.

Methods: Between November 2003 aid December 2008, 132 patients were transplanted, with a mean age of 52.0 years (range 3-71 years), of whom 98 were male (74%). Half of the patients had dilated cardiomyopathy and 33% ischemic cardiomyopathy. The mean age of donors was 31.7 years and 102 were male (77%). Donor hearts were harvested at a distance in 62% of cases. There was a gender mismatch between donor and recipient (F:M) in 19% of cases and ABO blood type disparity (not identical but compatible) in 11%. In all cases we used the technique of total transplantation with bicaval anastomosis, modified in this center. Mean ischemia time was 88.9 +/- 32.2 minutes. All patients received induction therapy with basiliximab and methylprednisolone.

Results: Six patients (4.5%) died within 30 days or during hospitalization, due to graft failure in four and hyperacute rejection in two. Two patients required prolonged ventilation, ten (8%) required inotropic support for more than 48 hours, and four required pacemaker implantation. Mean hospital stay was 15.6 +/- 15.2 days (median 13 days). Ninety percent of patients (116/129) were maintained on triple immunosuppressive therapy, including cyclosporine, the remainder receiving tacrolimus. In 23 patients it was necessary to change the immunosuppressive regimen due to renal and/or tumoral complications, or humoral rejection. All patients are followed regularly in the Surgical Center. Thirteen patients (10%) died late of cancer (6 patients), infection (4 patients), and pancreatitis, pulmonary hypertension and suicide (one patient each). Twenty-two patients (17%) had 25 episodes of cellular rejection (> or = 2R), with clinical consequences in only one case, and five had humoral rejection (3.9%). No patients died of late rejection, but there is evidence of mild graft vascular disease in one. Actuarial survival (Kaplan-Meier) at one and five years was 90% and 82%, respectively.

Conclusion: In this initial series of five years we obtained results equivalent to or bette than those in centers with wider and longer experience, aided by self-correction arising from our own experience. This program has increased the rate of cardiac transplantation in Portugal to above the European average.
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May 2010

Decomposing the determinants of health care expenditure: the case of Spain.

Eur J Health Econ 2012 Feb 19;13(1):19-27. Epub 2010 Sep 19.

Department of Economics, University of Cantabria, Avda. Los Castros, s/n. 39005, Santander, Spain.

The aim of this paper is to analyze the determinants of regional health-care expenditure in Spain. The coexistence of several models concerning the degree of spending power decentralization and financing systems makes Spain a singular case. It also allows us to draw conclusions relevant to other countries in decentralizing their health-care systems, and to understand cross-country differences with estimated parameters. Using data from the Spanish regions for the period 1992-2005, we show that the estimated health public expenditure income elasticity does change depending on the omission of relevant variables, econometric specifications and techniques, and institutional arrangements. Moreover, while demographic structure is a very relevant factor when explaining health-care expenditure dynamics, multicollinearity biases econometric parameter estimates.
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http://dx.doi.org/10.1007/s10198-010-0276-9DOI Listing
February 2012

Diabetes mellitus does not affect one-year outcome after heart transplantation.

Rev Port Cardiol 2010 Feb;29(2):205-20

Serviço de Cardiologia dos Hospitais da Universidade de Coimbra e Clínica Universitària de Cardiologia da Faculdade de Medicina de Coimbra, Coimbra, Portugal.

Background And Aims: Heart transplantation remains the gold standard treatment for selected patients with end-stage heart failure. However, transplantation in diabetic patients remains controversial. The hyperglycemic effect of immunosuppressant therapy further complicates posttransplantation management of diabetes and, although this is still unproven, could be responsible for a higher incidence of post-transplantation infection, rejection and mortality. In this study, we aimed to compare one-year outcomes of survival and morbidity after cardiac transplantation among recipients with and without diabetes mellitus.

Methods: This was a prospective observational study of 114 patients who underwent first heart transplantation between November 2003 and January 2008, with 1-year follow-up. They were divided into two groups according to whether they had pre-transplantation diabetes (group 1) or not (group 2). Baseline variables and complications were recorded. Logistic regression analysis was used to identify independent predictors of 1-year mortality.

Results: Of the 114 patients, 33% were diabetic before transplantation. Diabetic patients were older (57.0 +/- 7.4 vs. 51.2 +/- 12.9 years, p = 0.013), and had a higher prevalence of hypertension (63.6% vs. 16.7%, p = 0.002), lower creatinine clearance (53.5 +/- 16.2 vs. 63.0 +/- 21.8 ml/min, p = 0.020) and higher C-reactive protein levels (1.8 +/- 2.4 vs. 0.9 +/- 1.3 mg/l, p = 0.029) than non-diabetics. They tended to have more peripheral arterial disease (20.8 vs. 14.8%, p = NS) and carotid disease (25.8 vs. 14.3%, p = NS). In diabetic patients fasting glucose levels were significantly lower at one year than before heart transplantation (134.2 +/- 45.3 vs. 158.4 +/- 71.2 mg/dl, p = 0.039). There were no significant differences between diabetic and non-diabetic patients in rejection (16.2 vs. 23.4%, p = 0.467), infection (27.0 vs. 33.8%, p = 0.524) or mortality (16.2 vs. 6.5%, p = 0.171) at 1-year follow-up. On logistic regression analysis, the only predictor of 1-year mortality was baseline creatinine > 1.4 mg/dl (OR: 6.36, 95% CI: 1.12-36.04). Diabetes and impaired fasting glucose before heart transplantation were not independent predictors of 1-year mortality.

Conclusions: These data suggest that diabetes is not associated with worse 1-year survival or higher morbidity in heart transplant patients, as long as good blood glucose control is maintained.
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February 2010

Simultaneous cardiac and renal transplantation late after hepatic transplantation.

Eur J Cardiothorac Surg 2010 Nov 18;38(5):645-6. Epub 2010 Apr 18.

Centre of Cardiothoracic Surgery, University Hospital, Coimbra, Portugal.

Multiple organ transplantation is rarely performed because the combination in a single patient of the clinical conditions with that indication is uncommon. Besides, the scarcity of organ donors dictates a policy of maximisation of the results. We present the case of a patient who previously had a liver transplantation and was subsequently submitted to a successful simultaneous cardiac and renal transplantation.
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http://dx.doi.org/10.1016/j.ejcts.2010.03.009DOI Listing
November 2010

Uric acid: a prognostic marker not only before but also after heart transplantation.

Eur J Cardiothorac Surg 2010 Aug 24;38(2):187-91. Epub 2010 Feb 24.

Department of Cardiothoracic Surgery, University Hospital, Coimbra, Portugal.

Objectives: Early diagnosis of rejection after heart transplantation is mandatory, since even mild rejection can rapidly progress to more severe rejection. However, the identification of patients at high risk of acute cellular rejection and their non-invasive diagnosis remains a challenge. To identify patients with a high risk of acute cellular rejection during the first post-transplantation year.

Methods: A retrospective study of 114 consecutive patients submitted to first heart transplantation (between November 2003 and January 2008). The International Society for Heart and Lung Transplantation (ISHLT) grading system was used for the classification of endomyocardial biopsies. Patients were divided into two groups: group A (non-rejecting)--90 patients who had no significant rejection episodes (ISHLT grade <2R); and group B (rejecting)--included 24 patients with moderate or severe rejection episodes (grade > or =2R) during a 1-year post-transplantation follow-up. The Kaplan-Meier method was used for cumulative survival analysis with the Breslow test for assessing statistical differences between curves.

Results: The group B patients tended to have more ischaemic aetiology (42% vs 26%, p=0.13) and lower baseline triglycerides (99.1+/-34.2 vs 117.9+/-63.6 mg dl(-1), p=0.17), tended to receive less cardiac allografts from donors of the same ABO blood type (83% vs 92%, p=0.25) and to have longer cardiopulmonary bypass times (108+/-64 min vs 94+/-26 min, p=0.12). Significantly, they had more hyperuricaemia (71% vs 43%, p=0.02) and longer mechanical ventilation times (19.2+/-17.9h vs 14.3+/-5.3h, p=0.031). During follow-up, the group B patients tended to have more severe infections (46% vs 31%, p=0.16), to be more frequently Quilty-positive (50% vs 30%, p=0.073) and to have a higher 1-year mortality (8% vs 2%, p=0.18). Uric acid levels higher than 7.2 mg dl(-1) were identified as the optimal cut-off value to predict acute rejection after heart transplantation (with a sensitivity of 71%, a specificity of 62% and an area under the curve of 0.64).

Conclusions: Our work suggests that hyperuricaemia may be a marker of acute cellular rejection that could be another tool helping to identify acute rejection during the follow-up of cardiac-transplanted patients.
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http://dx.doi.org/10.1016/j.ejcts.2010.01.018DOI Listing
August 2010

Endocarditis of the mitral valve with left ventricular atrial fistula.

Eur J Cardiothorac Surg 2009 Dec 18;36(6):1078. Epub 2009 Aug 18.

Centre of Cardiothoracic Surgery, University Hospital, 3000-075 Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.ejcts.2009.06.031DOI Listing
December 2009

Cardiac allograft systolic function. Is the aetiology (ischaemic or idiopathic) a determinant of ventricular function in the heart transplant patient?

Interact Cardiovasc Thorac Surg 2008 Aug 8;7(4):586-90; discussion 590. Epub 2008 May 8.

Program of Heart Transplantation, Centre of Cardiothoracic Surgery, University Hospital, Coimbra, Portugal.

The natural history of the LV systolic function (LV-SF) and functional capacity of survivors of heart transplantation (Htx) has not been defined. Some investigators suggest that SF may be different in recipients with different pre-transplant aetiologies: ischaemic or dilated, idiopathic disease. Routine transthoracic echocardiograms (TTE) were performed during a 1-year follow-up in 48 Htx recipients (total 864 examinations; mean 18/patient). Patients were divided into two groups based on pre-transplant diagnosis: ischaemic (CAD-CMP: n=13, age 54+/-1.7 years, 23% females) and idiopathic dilated cardiomyopathy (ID-CMP: n=35, age 51+/-2.3 years, 26% females). Patients with valvular and toxic aetiology were excluded. All patients underwent left ventriculography (VENT) 12-15 months after Htx. The majority of 1-year survivors of Htx maintained normal LV-SF: mean LVEF 65+/-4% by echocardiography and 68+/-3% by ventriculography, but in the ID-CMP group LVEF was significantly higher: 67+/-4% vs. 62+/-4% (TTE) and 77+/-4% vs. 60+/-4% (VENT), without significant differences in functional capacity (NYHA). 82.9% of ID-CMP patients had LVEF >65% vs. 39% in CAD-CMP. The incidence of acute cellular rejection, freedom from cardiac vasculopathy, renal failure, diabetes, hypertension and pre-transplant alloantibody level was similar. Our study shows a strong correlation between pre-transplant heart disease and the systolic function of the cardiac allograft at 1-year follow-up.
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http://dx.doi.org/10.1510/icvts.2007.167924DOI Listing
August 2008
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