Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Hacia un mejor manejo de la insuficiencia cardiaca: papel de las unidades multidisciplinares y de la colaboración ntre niveles asistenciales en la continuidad de la asistencia: experiencia en el noroeste de Madrid / No disponible

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Genetic testing of candidate genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare cardiac genetic disease characterized by the presence of structural alterations in the right ventricle which may cause ventricular arrhythmias and may induce sudden cardiac death. ARVC/D has been associated with mutations in genes encoding myocyte adhesion proteins. However, only 30%-50% of patients have mutations in these genes. Genetic testing is useful in obtaining a diagnosis, particularly in individuals who do not completely fulfill clinical criteria, thereby also enabling the undertaking of preventive strategies in family members. The main goal of this study was to identify mutations in candidate genes associated with intercalate disks that could be potentially involved in ARVC/D pathogenesis. We analyze a cohort of 14 Spanish unrelated patients clinically diagnosed with ARVC/D without any genetic alteration in all previously known responsible genes. Thus, a genetic screening has been performed in 7 additional potential candidate genes (ACTC1 -actin alpha cardiac muscle 1-, CDHN -cadherin 2 type 1 or N-cadherin-, CTNNA1 -catenin alpha 1-, Cx43 or GJA1 -gap junction protein alpha 1-, MVCL -Metavinculin-, MYL2 -myosin light chain 2- and MYL3 -myosin light chain 3-) by direct sequencing analysis. Our genetic analysis did not identify any disease-causing mutation. Thirty single nucleotides polymorphisms were found, six of them novel. In conclusion, our ARVC/D Spanish cohort has not shown any mutations in the analyzed candidate genes despite their involvement in formation and maintenance of the intercalated disk.

Improvement in chronic renal failure after mycophenolate mofetil introduction and cyclosporine dose reduction: four-year results from a cohort of heart transplant recipients.

Chronic renal failure (CRF) due to calcineurin inhibitor (CNI) nephrotoxicity is a frequent complication among heart transplant (HT) recipients. Small studies have suggested that the introduction of mycophenolate mofetil (MMF) can help to reduce CNI doses thereby to maintaining or improving renal function. We conducted a 4-year, prospective, multicenter study in 89 maintenance HT recipients at 5.6 ± 2.7 years postgrafting who displayed CRF (serum creatinine > 1.4 mg/dL) and were undergoing treatment with cyclosporine and prednisone ± azathioprine. We introduced MMF and reduced cyclosporine to level below 100 ng/mL. Creatinine clearance (CrCl), acute rejection episodes, and survival were through retrospectively compared with a contemporary cohort of HT recipients who were not treated with MMF (control group; n = 38). After conversion to MMF, a rapid increase was observed in the CrCl, which was maintained over the follow-up: namely, CrCl at month 6 and at 4 years were 51.0 ± 15.6 and 54.1 ± 15.6 mL/min versus 41.9 ± 11.1 mL/min at baseline (P < .0001). No renal function changes were observed among the control group. Acute rejection rates were 5.6% and 2.6% in the MMF versus control groups (P = NS) with 4-year survivals >85%. In conclusion, the introduction of MMF allowed a safe reduction of cyclosporine and significantly improved renal function after 4 years.

Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

Incidence and risk factors for nonmelanoma skin cancer after heart transplantation.

INTRODUCTION: The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence. PATIENTS AND METHODS: We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure. RESULTS: The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P<.0005) and azathioprine (AZA) 1.8 (1.2-2.7; P<.0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant. CONCLUSION: Age at transplantation>45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).

Pseudomembranous Aspergillus tracheobronchitis in a heart transplant recipient.

Aspergillus tracheobronchitis (AT) is an uncommon clinical presentation of pulmonary aspergillosis that frequently progresses to invasive pulmonary aspergillosis. Diagnosis of AT may be delayed because of its insidious onset, non-specific signs and symptoms, and scarcity of radiographic abnormalities. We report the case of a patient who received a heart transplant (HT) because of cardiac amyloidosis and who developed pseudomembranous AT. Possible risk factors concurrent in this case were splenectomy, lymphocytopenia, and previous cytomegalovirus infection. Chest computed tomography scan showed thickening of the left bronchi and a 'tree-in-bud' pattern with multiple small nodules. Bronchoscopic examination revealed raised yellowish pseudomembranous plaques on the tracheobronchial tree. Bronchoalveolar lavage and aspirate cultures yielded Aspergillus fumigatus. The patient recovered with voriconazole. Clinicians should be aware of AT as a potential cause of respiratory symptoms with few radiographic abnormalities in HT recipients, as delay in performing bronchoscopy could result in an unfavorable prognosis.

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

[Epidemiological analysis of the improving areas for blood pressure control at Primary Care practice]. / Análisis de las áreas de mejora del control de la hipertensión arterial en Atención Primaria.

BACKGROUND AND OBJECTIVES: Most hypertensive patients do not have their blood pressure (BP) under control. This study aims to evaluate Primary Care physicians' management of hypertension by analyzing the four main areas proposed by experts to improve BP control. MATERIAL AND METHODS: From February to May 2003 a questionnaire was completed by 195 Primary Care physicians from 33 Primary Care centers of Madrid, Spain. Four aspects of clinical practice were examined: a) knowledge of hypertension guidelines and objectives; b) diagnosis and follow-up of patients; c) hypertension treatment, and d) drug compliance. RESULTS: Guidelines were followed by 90.6% of the physicians. Twenty six percent of the physicians perceived that guideline objectives are too strict and only 32% identified systolic BP as the component that provides more risk. Only 14% used automatic devices to measure BP while 89% still use the mercury sphygmomanometer. Diuretics were included among the 3 most used antihypertensive drugs by 94% of the physicians, ACEI by 91%, beta blockers by 62% and combinations only by 24%. Eighty eight percent believed that more than 40% of their patients have their BP under control and 53% felt that less than 20% of their patients were non-compliant with antihypertensive treatment. CONCLUSIONS: Hypertension management among Primary Care physicians showed some deficiencies in the 4 analyzed areas. Thus, perception of excessively rigorous guideline objectives, underrating of systolic BP, underuse of automatic devices and drug associations, and the overestimation of BP control and therapeutic compliance are specific areas that should be modified to improve BP control.

Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients--a large European trial.

We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized (1:1) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies, which underwent local and blinded central evaluation. The full analysis set comprised 157 patients per group. Patient/graft survival was 92.9% for Tac and 89.8% for CyA at 18 months. The primary end point, incidence of first biopsy proven acute rejection (BPAR) of grade >/= 1B at month 6, was 54.0% for Tac vs. 66.4% for CyA (p = 0.029) according to central assessment. Also, incidence of first BPAR of grade >/= 3A at month 6 was significantly lower for Tac vs. CyA; 28.0% vs. 42.0%, respectively (p = 0.013). Significant differences (p < 0.05) emerged between groups for these clinically relevant adverse events: new-onset diabetes mellitus (20.3% vs. 10.5%); post-transplant arterial hypertension (65.6% vs. 77.7%); and dyslipidemia (28.7% vs. 40.1%) for Tac vs. CyA, respectively. Incidence and pattern of infections over 18 months were comparable between groups, as was renal function. Primary use of Tac during antibody induction resulted in superior prevention of acute rejection without an associated increase in infections.

Análisis de las áreas de mejora del control de la hipertensión arterial en Atención Primaria / Epidemiological analysis of the improving areas for blood pressure control at Primary Care practice

Fundamento y objetivo. La mayoría de los hipertensos no tienen sus cifras de presión arterial (PA) controladas. Este estudio pretende conocer el manejo de la hipertensión arterial (HTA) por médicos de Atención Primaria en su práctica diaria analizando las cuatro grandes áreas de mejora del control propuestas por los expertos. Material y métodos. Desde febrero a mayo de 2003 se administró una encuesta a 195 médicos de Atención Primaria procedentes de 33 Centros de Salud de la Comunidad de Madrid. El cuestionario estudia 4 aspectos de la práctica clínica: a) conocimiento de las guías de HTA y objetivos terapéuticos; b) diagnóstico y seguimiento de pacientes hipertensos; c) tratamiento de la HTA, y d) cumplimiento terapéutico. Resultados. El 90,6% de los médicos sigue alguna guía acreditada. Para el 26% los objetivos terapéuticos de las guías son demasiado rigurosos y sólo el 32% identificó la presión sistólica como la que mayor riesgo confiere. Sólo el 14% utiliza dispositivos automáticos de brazo para medir la PA y el 89% utiliza esfigmomanómetros de mercurio. Para el 94% los diuréticos están entre los 3 fármacos más utilizados, los inhibidores de la enzima conversora de la angiotensina (IECA) para el 91%, los bloqueadores beta para el 62% y las combinaciones sólo para el 24%. El 88% cree que más del 40% de sus pacientes tienen su PA controlada. El 53% opina que menos del 20% de sus pacientes incumple/abandona el tratamiento antihipertensivo. Conclusiones. Se han identificado deficiencias en el manejo de la HTA en las 4 áreas analizadas. Así, la percepción de un excesivo rigor en los objetivos de las guías, el menosprecio de la presión sistólica, la infrautilización de los tensiómetros automáticos y de las asociaciones farmacológicas y la sobreestimación del control y del cumplimiento terapéutico son aspectos a corregir para incrementar el control de la PA (AU)

Background and objectives. Most hypertensive patients do not have their blood pressure (BP) under control. This study aims to evaluate Primary Care physicians' management of hypertension by analyzing the four main areas proposed by experts to improve BP control. Material and methods. From February to May 2003 a questionnaire was completed by 195 Primary Care physicians from 33 Primary Care centers of Madrid, Spain. Four aspects of clinical practice were examined: a) knowledge of hypertension guidelines and objectives; b) diagnosis and follow-up of patients; c) hypertension treatment, and d) drug compliance. Results. Guidelines were followed by 90.6% of the physicians. Twenty six percent of the physicians perceived that guideline objectives are too strict and only 32% identified systolic BP as the component that provides more risk. Only 14% used automatic devices to measure BP while 89% still use the mercury sphygmomanometer. Diuretics were included among the 3 most used antihypertensive drugs by 94% of the physicians, ACEI by 91%, beta blockers by 62% and combinations only by 24%. Eighty eight percent believed that more than 40% of their patients have their BP under control and 53% felt that less than 20% of their patients were non-compliant with antihypertensive treatment. Conclusions. Hypertension management among Primary Care physicians showed some deficiencies in the 4 analyzed areas. Thus, perception of excessively rigorous guideline objectives, underrating of systolic BP, underuse of automatic devices and drug associations, and the overestimation of BP control and therapeutic compliance are specific areas that should be modified to improve BP control (AU)

[Neurological complications in a series of 205 orthotopic heart transplant patients]. / Complicaciones neurológicas en una serie de 205 trasplantes cardíacos ortotópicos.

INTRODUCTION: A heart transplant is the only effective therapeutic option open to many patients with severe heart failure and performing such an intervention is not free of complications. Little is known about the risk factors for neurological complications after a heart transplant. AIMS: The aim of this study was to identify the risk factors for neurological complications following a heart transplant and, more especially, those associated with epileptic seizures, encephalopathy, cerebrovascular accidents (CVA) and headaches. PATIENTS AND METHODS: We conducted a retrospective review of the records of 205 orthotopic heart transplant patients and collected clinical, haemodynamic and laboratory data before, during and after the intervention, using a standardised protocol. RESULTS: 95 patients (48%) presented neurological complications. Their frequencies were as follows: encephalopathy (16.6%), epileptic seizures (13.6%), neuromuscular disorders (10.6%), headaches (10.6%), CVA (10.1%), psychiatric disorders (2.2%) and infection of the central nervous system (2.2%). The risk factors for encephalopathy were post-transplant renal failure (RR: 4.6; CI 95%: 1.4-15), post-transplant hepatic failure (RR: 5.6; CI 95%: 1.5-22) and pre-transplant haemodynamic instability (RR: 4.3; CI 95%: 1.3-14); for epileptic seizures they were a cardiac index of < or = 2 L/min/m2 (RR: 23.8; CI 95%: 2-247) and extracorporeal circulation time > or = 115 min (RR: 11.3; CI 95%: 1-79); and for CVA the risk factor was post-transplant hepatic failure (RR: 12.9; CI 95%: 2.5-66). CONCLUSIONS: Neurological complications often occur after a transplant and are transient. Perioperative haemodynamic instability giving rise to cerebral ischemia and the metabolic disorders secondary to multiple organ failure are determining factors of encephalopathy, epileptic seizures and CVA.

Complicaciones neurológicas en una serie de 205 trasplantes cardíacos ortotópicos / Neurological complications in a series of 205 orthotopic heart transplant patients

Introducción. El trasplante cardíaco es la única opción terapéutica efectiva para muchos pacientes con insuficiencia cardíaca grave, pero su realización no está exenta de complicaciones. Los factores de riesgo de complicaciones neurológicas después del trasplante cardíaco se conocen poco. Objetivos. Identificar los factores de riesgo de complicaciones neurológicas tras un trasplante cardíaco, especialmente los asociados con crisis epilépticas, encefalopatía, accidente cerebrovascular (ACV) y cefalea. Pacientes y métodos. Se revisaron de forma retrospectiva las historias clínicas de 205 pacientes con trasplantes cardíacos ortotópicos y se recogieron los datos clínicos, hemodinámicos y de laboratorio, antes, durante y después de la cirugía, según un protocolo estandarizado. Resultados. Hubo 95 pacientes (48 por ciento) que presentaron complicaciones neurológicas. Fueron encefalopatía (16,6 por ciento), crisis epilépticas (13,6 por ciento), alteración neuromuscular (10,6 por ciento), cefalea (10,6 por ciento), ACV (10,1 por ciento), trastornos psiquiátricos (2,2 por ciento) e infección del sistema nervioso central (2,2 por ciento). Los factores de riesgo para la encefalopatía fueron la insuficiencia renal postrasplante (RR: 4,6; IC 95 por ciento: 1,4-15), la insuficiencia hepática postrasplante (RR: 5,6; IC 95 por ciento: 1,5-22) y la inestabilidad hemodinámica pretrasplante (RR: 4,3; IC 95 por ciento: 1,3-14); para las crisis epilépticas fueron índice cardíaco = 115 min (RR: 11,3; IC 95 por ciento: 1-79), y para el ACV fue la insuficiencia hepática postrasplante (RR: 12,9; IC 95 por ciento: 2,5-66). Conclusiones. Las complicaciones neurológicas postrasplante son frecuentes y transitorias. La inestabilidad hemodinámica perioperatoria productora de isquemia cerebral y las alteraciones metabólicas secundarias a fallo multiorgánico son determinantes de encefalopatía, crisis epilépticas y ACV (AU)

Introduction. A heart transplant is the only effective therapeutic option open to many patients with severe heart failure and performing such an intervention is not free of complications. Little is known about the risk factors for neurological complications after a heart transplant. Aims. The aim of this study was to identify the risk factors for neurological complications following a heart transplant and, more especially, those associated with epileptic seizures, encephalopathy, cerebrovascular accidents (CVA) and headaches. Patients and methods. We conducted a retrospective review of the records of 205 orthotopic heart transplant patients and collected clinical, haemodynamic and laboratory data before, during and after the intervention, using a standardised protocol. Results. 95 patients (48%) presented neurological complications. Their frequencies were as follows: encephalopathy (16.6%), epileptic seizures (13.6%), neuromuscular disorders (10.6%), headaches (10.6%), CVA (10.1%), psychiatric disorders (2.2%) and infection of the central nervous system (2.2%). The risk factors for encephalopathy were post-transplant renal failure (RR: 4.6; CI 95%: 1.4-15), post-transplant hepatic failure (RR: 5.6; CI 95%: 1.5-22) and pre-transplant haemodynamic instability (RR: 4.3; CI 95%: 1.3-14); for epileptic seizures they were a cardiac index of ≤ 2 L/min/m2 (RR: 23.8; CI 95%: 2-247) and extracorporeal circulation time ≥ 115 min (RR: 11.3; CI 95%: 1-79); and for CVA the risk factor was post-transplant hepatic failure (RR: 12.9; CI 95%: 2.5-66). Conclusions. Neurological complications often occur after a transplant and are transient. Perioperative haemodynamic instability giving rise to cerebral ischemia and the metabolic disorders secondary to multiple organ failure are determining factors of encephalopathy, epileptic seizures and CVA (AU)

Differential characteristics of heart transplantation in patients older than 60 years.

BACKGROUND: The effect of advanced age on the results of heart transplantation (HTx) is still controversial. The few articles addressing this issue have not been conclusive, due to either short follow-up periods or small numbers of patients. METHODS: We present a retrospective study of 560 HTx which were divided into group A, including patients of 60 or less years at HTx (n=465, 83%), and group B, of 95 recipients older than 60 years. A subgroup of the latter, named B1, includes 24 patients older than 65. More than 100 recipient, donor and surgical procedure variables were analyzed for their impact on actuarial survival and incidence of common causes of posttransplant morbidity and mortality during a follow-up period longer than 10 years. RESULTS: Group B showed a lower number of acute rejection episodes than group A, (1.53+/-1.87 versus 1.96+/-1.81, P<.04). Both groups showed a similar incidence of infection episodes, malignancies or graft vasculopathy, but older patients experienced fewer viral infections than younger ones (9% in group A versus 18% in group B, P<.05). Log-rank test showed a trend to shorter survival in group B (P=.08), a disadvantage that reached significance (P=.01) among patients older than 65 years. CONCLUSIONS: Patients who were older than 60 at HTx displayed a lower incidence of acute rejection episodes and viral infections, but a trend toward shorter long-term survival. This disadvantage in prognosis was statistically significant among recipients older than 65 years.

Rapamycin in lung transplantation: preliminary results.

INTRODUCTION: Rapamycin is a potent immunosuppressive agent with a different mechanism of action and different adverse effects from those of calcineurin inhibitors (CNIs). OBJECTIVE: To analyze our experience with rapamycin in patients undergoing lung transplantation and heart-lung transplantation in our center. PATIENTS AND METHODS: Patients were treated with rapamycin when showing chronic rejection and/or toxicity associated with the CNI after lung transplantation or heartlung transplantation. Patients with chronic rejection were administered rapamycin in combination with CNIs, whereas the CNIs were eliminated in patients with toxicity. RESULTS: Since October 2001, 7 patients (4 women), of mean age 45+/-15 years, received treatment with rapamycin (heart-lung transplantation, 2 cases; lung transplantation, 5 cases). The indications were chronic rejection in 4 patients and CMIs toxicity in 3 patients (kidney failure in 2 cases and optic neuropathy in 1 case). Pulmonary function stabilization was observed in 3 of 4 patients receiving rapamycin for chronic rejection. In the 3 patients with CNIs toxicity elimination of these drugs did not result in pulmonary functional deterioration. Patients with kidney failure showed an improvement in creatinine levels; visual acuity improved in the patient with optic neuropathy. We observed 2 infectious complications (pneumococcal pneumonia and pulmonary aspergillosis), which resolved with treatment. CONCLUSION: Rapamycin is an alternative for lung-transplant recipients who develop chronic rejection and/or CNIs toxicity.

High incidence of severe infections in heart transplant recipients receiving tacrolimus.

BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx). It is believed to engender slightly more powerful protection against acute rejection. However, the increased immunosuppression could result in an excess of infectious complications. METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84). RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK. Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients. After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year. Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05). Among the FK group, the most common site of MInf was pulmonary (69%). A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria. There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy. CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients. We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx.

Pulmonary nocardiosis in heart transplant recipients: treatment and outcome.

BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients. The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients. METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002. RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up). All patients had pulmonary disease and one in addition had subcutaneous nodules. Microbiological diagnosis required open lung biopsy in one case. All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases. Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism. Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years. In one case a cutaneous recurrence of disease was attributed to noncompliance. CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported. Its incidence seems to be delayed in time with modern immunosuppressants. Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity. We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population.