Interdisciplinary Mobile Health Model to Improve Clinical Care After Heart Transplantation: Implementation Strategy Study.

BACKGROUND: Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. OBJECTIVE: The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. METHODS: This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. RESULTS: An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. CONCLUSIONS: The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory-based mHealth strategy.

Design of the ß3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial.

Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (ß3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available ß3AR agonist) in patients with CpcPH due to HF. The effect of ß3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539).

Sacubitril/Valsartan in Real-Life Practice: Experience in Patients with Advanced Heart Failure and Systematic Review.

PURPOSE: Sacubitril/valsartan reduced heart failure (HF) admissions and cardiovascular mortality in the PARADIGM-HF trial. However, real-life studies are scarce comparing daily practice patients with those of the trial. The aim of our study was to analyze the efficacy and safety of the drug in an advanced heart failure cohort and to review systematically the previous real-life studies published to date. METHODS: We performed a retrospective analysis of consecutive patients prescribed sacubitril/valsartan in a single tertiary HF clinic between September 2016 and February 2018. HF admissions before and after the initiation of the drug were assessed in a paired fashion. A systematic review of real-life studies published to date was also conducted. RESULTS: Sacubitril/valsartan was started in 108 patients who were in a more advanced NYHA class and more frequently treated with mineral receptor antagonists, internal cardiac defibrillator, and cardiac resynchronization therapy than in the PARADIGM-HF trial. After a 6-month follow-up, we observed a significant reduction in the HF hospitalizations, median levels of NT-proBNP, and need for levosimendan ambulatory perfusion. Likewise, we found a significant improvement in mean LVEF and end diastolic left ventricle diameter. Regarding safety, sacubitril/valsartan was well-tolerated without any severe adverse effect. CONCLUSION: Sacubitril/valsartan in real-life is prescribed to a more advanced HF population, which could be responsible for the difficulties in reaching high doses of the drug. However, after a 6-month follow-up, sacubitril/valsartan significantly reduces HF hospitalization and induces cardiac reverse remodeling, without remarkable adverse events.

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

ANTECEDENTS: Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. AIM: Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. METHODS: 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. RESULTS: 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015-1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001-1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). CONCLUSION: Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.

Cancer antigen-125 and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Cancer antigen-125 (Ca-125) is traditionally recognised as a tumour marker and its role in cardiovascular diseases has been studied only in recent years. Whether Ca-125 is elevated in patients with atrial fibrillation (AF) and its levels predict the risk of AF remains controversial. Therefore, we conducted a systematic review and meta-analysis of the association between Ca-125 levels and AF. METHODS: PubMed and EMBASE databases were searched until 1 June 2017 for studies that evaluated the association between Ca-125 and AF. Inclusion criteria included studies that compare Ca-125 in patients with and without AF, or those reporting HRs/ORs for risk of AF stratified by Ca-125 levels. RESULTS: A total of 39 entries were retrieved from the databases, of which 10 studies were included in the final meta-analysis. Ca-125 was significantly higher in patients with AF compared with those in sinus rhythm (mean difference=16 U/mL, 95% CI 2 to 30 U/mL, P<0.05; I2: 98%). Ca-125 significantly increased the risk of AF (HR: 1.39, 95% CI 1.06 to 1.82, P<0.05; I2: 84%). CONCLUSION: Ca-125 was significantly higher in patients with AF than in those in sinus rhythm, and high Ca-125 is predictive of AF occurrence. However, the high heterogeneity observed means there is an uncertainty in the relationship between Ca-125 and AF, which needs to be confirmed by larger prospective studies.

Spanish Heart Transplantation Registry. 26th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2014).

INTRODUCTION AND OBJECTIVES: We present the characteristics and outcomes of heart transplantation in Spain since it was first performed in 1984. METHODS: A descriptive analysis of the characteristics of recipients, donors, the surgical procedure, and the outcomes of heart transplantations performed in Spain until 31 December 2014. RESULTS: In 2014, 266 procedures were performed, making a time series of 7289 transplantations. The temporal analysis confirmed a significant worsening of the clinical profile of recipients (higher percentage of older patients, patients with severe renal failure, insulin-dependent diabetes, previous cardiac surgery, and previous mechanical ventilation), of donors (higher percentage of older donors and greater weight mismatch), and of the procedure (higher percentage of emergency transplantations, reaching 41.4% in 2014, and ischemia time>240min). Mechanical assist devices were used less than in 2013; in 2014 they were used in 18.8% of all transplant recipients. Survival at 1, 5, 10, and 15 years was 76%, 65%, 52%, and 38%, respectively, and has remained stable since 1995. CONCLUSIONS: Cardiac transplantation activity in Spain has remained stable in recent years, at around 250 procedures per year. Despite a clear deterioration in donor and recipient characteristics and surgical times, the mortality outcomes have remained comparable to those of previous periods in our environment. The growing use of circulatory assist devices before transplantation is also confirmed.

Prevalence of Stable Angina in Spain. Results of the OFRECE Study.

INTRODUCTION AND OBJECTIVES: The objective of the OFRECE study was to estimate the prevalence of stable angina in Spain. This prevalence is currently unknown, due to a lack of recent studies and to changes in the epidemiology and treatment of ischemic heart disease. METHODS: This cross-sectional study involved a representative sample of the Spanish population aged 40 years or older, obtained via 2-stage random sampling: in the first stage, primary care physicians were randomly selected from each Spanish province, whereas in the second stage 20 people were selected from the population assigned to each physician. The prevalence was weighted by age, sex, and geographical area. Participants were classified as having angina if they met the "definite angina" criteria of the Rose questionnaire and as having confirmed angina if the angina was confirmed by a cardiologist or if they had a history of acute ischemic heart disease or revascularization. RESULTS: Of the 11 831 people invited to participate, 8378 (71%) were analyzed (mean age, 59.2 years). The weighted prevalence of definite angina (Rose) was 2.6% (95% confidence interval, 2.1%-3.1%) and was higher in women (2.9%) than in men (2.2%), whereas that of confirmed angina was 1.4% (95% confidence interval, 1.0%-1.8%), without differences between men (1.5%) and women (1.3%). The prevalence of definite angina (Rose) increased with age (0.7% in patients aged 40 to 49 years and 7.1% in those aged 70 years or older), history of cardiovascular disease, and cardiovascular risk factors, except smoking. CONCLUSIONS: The prevalence of definite angina (Rose) in the Spanish population aged 40 years or older was 2.6%, whereas that of confirmed angina was 1.4%. Both prevalences increased with age, cardiovascular risk factors, and cardiovascular history.

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.

Heart transplantation using allografts from older donors: Multicenter study results.

BACKGROUND: The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors. METHODS: We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors. RESULTS: There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs. 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18-1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22-2.27; p = 0.001). CONCLUSIONS: There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.

CD4+CD45RO+CD25-/lowCD127+: CD4+CD45RO+CD25hiCD127-/low Ratio in Peripheral Blood: A Useful Biomarker to Detect Cardiac Allograft Vasculopathy in Heart Transplanted Patients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major limitation in long-term graft survival after heart transplantation (HTx). Its prediction and detection at an early stage is a challenge because an accurate, minimally invasive blood test is lacking. The aim of this study was to analyze the relationship of Tact (CD4CD45ROCD25-CD127) cells, Th1 cells, and thymus-derived regulatory (Treg) (CD4CD45ROCD25CD127) cells in peripheral blood with the development of CAV in HTx patients. METHODS: First, we performed a cross-sectional study in 29 patients at least 2 years after HTx, 17 with CAV and 12 without CAV. We then prospectively followed a group of 38 patients for 2 years immediately after HTx surgery. In both groups, we analyzed the relationship between CAV and the effector-to-regulatory T cell ratio. RESULTS: In the cross-sectional study, patients with CAV showed statistically significant higher values of Th1-to-FoxP3Treg and Tact-to-CD127Treg ratios than non-CAV patients, with P less than 0.01 and P less than 0.001, respectively. Receiver operating characteristic curve analysis showed that the Tact:CD127Treg ratio was a potential biomarker of CAV, clearly discriminating CAV and non-CAV patients (area under curve [AUC] = 0.955; P = 0.001). In the prospective part of the study, we monitored the Th1:FoxP3Treg and Tact:CD127Treg ratios using the best tradeoff between anterior receiver operating characteristic sensitivity and specificity as a cutoff. Changes in the Tact:CD127Treg ratio were detected earlier than changes in the Th1:FoxP3Treg ratio. Both ratios were higher in HTx patients with CAV. CONCLUSION: The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.

Spanish Heart Transplantation Registry. 25th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2013).

INTRODUCTION AND OBJECTIVES: The present article reports the characteristics and outcome of heart transplantation in Spain since it was first performed in May 1984. METHODS: We provide a descriptive analysis of the characteristics of the recipients, the donors, the surgical procedure, and results of the heart transplantations performed in Spain until 31 December 2013. RESULTS: During 2013, a total of 248 transplantation procedures were carried out, bringing the time series to a total of 7023 transplantations. The temporal analysis confirms a significant deterioration in the clinical profile of the recipients (higher percentage of older patients, severe renal failure, insulin-dependent diabetes mellitus, previous heart surgery, mechanical ventilation), of the donors (higher proportion of older donors and greater weight mismatch), and of the procedure (higher percentage of emergency transplantations which, in 2013, reached 49%, and with ischemia times > 240min). There was a marked increase in the use of circulatory assist devices prior to transplantation which, in 2013, were employed in 25.2% of all the patients. The survivals at 1, 5, 10, and 15 years were 76%, 65%, 52%, and 37%, respectively, and have remained stable since 1995. CONCLUSIONS: Heart transplantation activity in Spain remains stable in recent years, with around 250 procedures a year. Despite the clear deterioration in the clinical characteristics of the donors and recipients, and lengthening of the operative times, the results in terms of mortality continue to be comparable to those reported in our neighboring countries, and a growing use of circulatory assist devices prior to transplantation is confirmed.

Initial experience of percutaneous treatment of mitral regurgitation with MitraClip® therapy in Spain.

INTRODUCTION AND OBJECTIVES: Symptomatic mitral regurgitation has an unfavorable prognosis unless treated by surgery. However, the European registry of valvular heart disease reports that 49% of patients with this condition do not undergo surgery. Percutaneous treatment of mitral regurgitation with MitraClip® has been proved a safe, efficient adjunct to medical treatment in patients with this profile. The objective of the present study is to describe initial experience of MitraClip® therapy in Spain. METHODS: Retrospective observational study including all patients treated between November 2011 and July 2013 at the 4 Spanish hospitals recording the highest numbers of implantations. RESULTS: A total of 62 patients (77.4% men) were treated, mainly for restrictive functional mitral regurgitation (85.4%) of grade III (37%) or grade IV (63%), mean (standard deviation) ejection fraction 36% (14%), and New York Heart Association functional class III (37%) or IV (63%). Device implantation was successful in 98% of the patients. At 1 year, 81.2% had mitral regurgitation ≤ 2 and 90.9% were in New York Heart Association functional class ≤ II. One periprocedural death occurred (sepsis at 20 days post-implantation) and another 3 patients died during follow-up (mean, 9.1 months). Two patients needed a second implantation due to partial dehiscence of the first device and 2 others underwent heart transplantation. CONCLUSIONS: In Spain, MitraClip® therapy has principally been aimed at patients with functional mitral regurgitation, significant systolic ventricular dysfunction, and high surgical risk. It is considered a safe alternative treatment, which can reduce mitral regurgitation and improve functional capacity.

Spanish Heart Transplantation Registry. 24th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2012).

INTRODUCTION AND OBJECTIVES: The present article reports the characteristics and results of heart transplantation in Spain since this therapeutic modality was first used in May 1984. METHODS: We summarize the main features of recipients, donors, and surgical procedures, as well as the results of all heart transplantations performed in Spain until December 31, 2012. RESULTS: A total of 247 heart transplantations were performed in 2012. The whole series consisted of 6775 procedures. Recent years have seen a progressive worsening in the clinical characteristics of recipients (34% aged over 60 years, 22% with severe kidney failure, 17% with insulin-dependent diabetes, 29% with previous heart surgery, 16% under mechanical ventilation) and donors (38% aged over 45 years, 26% with recipient: donor weight mismatch>20%), and in surgical conditions (29% of procedures at >4 h ischemia and 36% as emergency transplantations). The probability of survival at 1, 5, 10, and 15 years of follow-up was 78%, 67%, 53%, and 38%, respectively. These results have remained stable since 1995. CONCLUSIONS: In recent years, the number of heart transplantations/year in Spain has remained stable at around 250. Despite the worsening of recipient and donor clinical characteristics and of time-to-surgery, the results in terms of mortality have remained stable and compare favorably with those of other countries.

Clinical recommendations for the use of everolimus in heart transplantation.

Proliferation signal inhibitors (PSIs), everolimus (EVL), and sirolimus are a group of immunosuppressor agents indicated for the prevention of acute rejection in adult heart transplant recipients. Proliferation signal inhibitors have a mechanism of action with both immunosuppressive and antiproliferative effects, representing an especially interesting treatment option for the prevention and management of some specific conditions in heart transplant population, such as graft vasculopathy or malignancies. Proliferation signal inhibitors have been observed to work synergistically with calcineurin inhibitors (CNIs). Data from clinical trials and from the growing clinical experience show that when administered concomitantly with CNIs, PSIs allow significant dose reductions of the latter without loss of efficacy, a fact that has been associated with stabilization or significant improvement in renal function in patients with CNI-induced nephrotoxicity. The purpose of this article was to review the current knowledge of the role of PSIs in heart transplantation to provide recommendations for the proper use of EVL in cardiac transplant recipients, including indications, treatment regimens, monitoring, and management of the adverse events.

Severe aortic regurgitation and reduced left ventricular ejection fraction: outcomes after isolated aortic valve replacement and combined surgery.

BACKGROUND: In patients with severe aortic regurgitation and reduced left ventricular ejection fraction (LVEF), uncertainty remains whether to recommend aortic valve replacement (AVR) over heart transplantation, especially when mitral regurgitation and/or coronary heart disease coexist. METHODS: We assessed outcomes in 26 consecutive AVR patients aged

Assessment of peripheral endothelial-dependent vasodilatation within the first year after heart transplantation.

BACKGROUND: Peripheral endothelial dysfunction (ED) has been found in patients with severe heart failure. Whether ED improves after heart transplantation (HTx) is still a matter of controversy. METHODS: Forearm endothelium-dependent vasoreactivity was assessed in 40 patients after HTx. Flow-mediated vasodilatation (FMD) was measured by high-resolution brachial artery ultrasound to assess endothelial function at 1, 6, and 12 months after HTx. Cardiac allograft vasculopathy (CAV) was assessed by coronary angiography at 1 and 12 months and by intravascular ultrasound (IVUS) at 1 year. RESULTS: Mean FMD at 1 month was 1.9% +/- 2.6%, improving to 3.3% +/- 3.2% at 6 months (p < 0.005) and to 5.1% +/- 3.4% at 1 year (p < 0.0001). FMD was significantly impaired in 33 patients (82%) at 1 month, in 27 (67%) at 6 months, and in 19 (47%) at 1 year after HTx. CAV was diagnosed by IVUS in 19 patients (63%) at 1 year. Patients without peripheral ED at 1 month had lower incidence of increased intimal thickness of 0.5 mm or more at 1 year after HTx (20% vs 75%, p < 0.01). CONCLUSIONS: Impairment of peripheral FMD was highly prevalent soon after HTx and was present in nearly 50% of patients at 1 year. Patients without peripheral ED at 1 month were associated with lower probability of CAV. Although more studies are needed, the evaluation of peripheral endothelial function at 1 month after HTx could be potentially useful to identify patients at lower risk of CAV.

Effects of cyclosporine, tacrolimus and sirolimus on vascular changes related to immune response.

BACKGROUND: Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation. METHODS: Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts. RESULTS: At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p < 0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods. CONCLUSIONS: SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.

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.