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.

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.

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.

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%).

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.

[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.

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.

[Angina pectoris in the heart transplant recipient: evidence of reinnervation]. / Angina de pecho en el paciente con trasplante cardíaco: una evidencia de reinervación.

Heart transplantation involves the removal of a sick heart together with its innervation and replacement with a donor heart isolated from the control of the autonomous nervous system of the recipient, therefore being, functionally dennervated. Dennervation conditions several alterations in cardiac physiology, such as the inability to experience pain during myocardial ischemia, so that theoretically these patients cannot present angina pectoris. However, several reports have shown evidence of reinnervation with isolated cases of transplanted patients with angina pectoris having been reported. We describe the case of a transplanted patient who showed typical effort angina, vascular disease of the graft and data of sympathetic reinnervation demonstrated by cardiac gammagraphy with metayodo-benzilguanidina-I-123.

[The heart transplantation in Spain. Organization and results]. / El trasplante cardíaco en España. Organización y resultados.

Heart transplantation has achieved a great development in Spain. With 8 heart transplantation procedures per million of inhabitants per year, we are the second ranking country, after the U.S.A., in this therapeutic activity. A relative adequacy between the number of available donors and the number of receptors included on the waiting list help to reduce the delays and the mortality rates in expecting patients, compare to other countries, which demonstrated the efficiency of the system. From 1984 to 1998, 2,756 heart transplantations were performed in Spain, in 16 authorized hospitals. In 56 cases (2%) the procedures were re-transplantation. Cardiomyopathy with ischemic origin was the most frequent pathology in determining the intervention, affecting to the 37% of the receptors, followed by idiopathic dilated cardiomyopathy with a 35%. Compared to other countries, a high proportion of cardiopathies (11%) of rheumatic origin stands out.20% of the heart transplantations were performed in a maximum emergency situation of the receptors. Assigning donors priority on a national scale. In a 2, 9% of the cases, extra procedures of circulatory assistance devises were used. The actuarial survival of the whole series is 74% at the end of the first year; 62% after five years and 46% after ten years. The mean survival of the grafts was 9.5 years. These data do not differ substantially from those of the Registry of the International Society of Heart and Lung Transplantation. The most important causes of early mortality were the graft primary failure, the infections and the rejection. Among the causes of late morbidity, cancer, with a prevalence of 6,1%, and vascular disease of the graft, present in 8,4% of the receptors, stand out. These results support the so-called Spanish Model for Solid Organ Transplantation, which, according to the health authorities of the European Union, should be implemented in all the member countries. The keys to the success of the Spanish Model are based on three factors, in order of importance: a) to have a public professionalized institution for the detection of donors, the allocation of the grafts, and the coordination of the extraction and transportation force. The Transplant National Organization is the name of this complex force in our country; b) the high rates of road and labour mortality in Spain, and c) to provide incentives for the professionals in charge of the whole process.

Visceral leishmaniasis (kala-azar) in solid organ transplantation: report of five cases and review.

Visceral leishmaniasis is an infectious disease that occurs only rarely in recipients of solid organ grafts but is associated with an elevated mortality rate despite proper treatment. We report five cases diagnosed in our hospital. All the patients were men aged 30 to 60 years who had undergone kidney transplantation (3 patients), heart transplantation (1), or liver transplantation (1). Three of the patients died, one had multiple recurrences, and one developed post-kala-azar cutaneous leishmaniasis. We review the clinical features, treatments, and outcomes of 26 previously reported cases, pointing out the lower cure rate associated with human immunodeficiency virus infection.

[Practice guidelines of the Spanish Society of Cardiology. Cardiac and heart-lung transplants]. / Guías de actuación clínica de la Sociedad Española de Cardiología. Trasplante cardíaco y de corazón-pulmones.

Cardiac transplantation is the only therapy that is able to substantially modify the natural evolution of patients with severe heart failure, along with angiotensin converting enzyme inhibitors. Nevertheless, because of the limited number of donors, its impact is scarce compared to the magnitude of the problem. Up to the end of 1998, 48,541 orthotopic cardiac transplantations and about 2,510 heart and both lung transplantations have been registered throughout the world. In Spain 2,780 procedures have been performed in the last 15 years. The survival expectations for a transplanted patient is 75% after the first year and 60% the following 5 years. The average duration of the graft is 8 years and 6 months. Cardiac transplantation is indicated for young and middle-age patients with irreversible cardiac process in bad clinical condition, with no other possibility of medical or surgical management and with a limited life expectancy. The major debate when choosing this therapy appears with the critical patients, patients older than 65 years, and some patients with systemic diseases. The great demand of transplantation obliges the teams to enlarge the criteria for donors' acceptance. At the same time, the increase of the knowledge about the transmission of some infections, mainly viral, forces to review those criteria day-to-day. The use of different immunosuppressive strategies pursues the control of rejection. The most commonly used is the so-called triple therapy (cyclosporine-azathioprine and steroids). The use of antilymphocytic antibodies such as cytolytic induction treatment is not unanimously accepted. Some of the new immunosuppressive agents such as myphenolate-mofetil and tacrolimus seem to offer advantages mainly due to their greater potency. Since transplantation is a limited procedure, of which its practise has an effect on the whole health system of a country, a perfect planning and adequacy of the Centers is compulsory, as well as the setting-up of clear rules for the use of donors and priority of transplantation. Finally, the patient must be informed clearly and comprehensively at length of the risks, limitations and expectations of these complex procedures.

[Experimental endocarditis. Pathological anatomy of human endocarditis]. / Endocarditis experimental. Anatomía patológica de la endocarditis humana.

Experimental reproduction of human endocarditis in animal models has been based on the induction of structural lesions in valve endocardium using different methods. The primary lesion caused in this way is the so called non-bacterial thrombotic endocarditis. Its colonization is then induced by inoculation of microorganisms in the bloodstream. Freedman's modified method has been the most widespread model of this type. It has mainly been performed in rabbits with inoculation of Staphylococcus aureus or alpha-hemolitic Streptococcus. Experimental models of endocarditis have contributed to our knowledge of the pathogenic mechanisms, causative agents and predisposing factors of endocarditis. They have also allowed us to develop appropriate diagnostic, therapeutic and prophylactic measures for its management.

Detection of herpesvirus-like sequences in Kaposi's sarcoma from heart transplant recipients.

BACKGROUND: Herpesvirus-like DNA sequences have been found in lesions from patients with Kaposi's sarcoma in its several forms, suggesting that this tumor may be caused by a new herpesvirus, referred to as Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8. METHODS: We analyzed DNA from skin and lung lesions, healthy skin, and peripheral blood mononuclear cells of three heart transplant recipients with Kaposi's sarcoma. We also studied DNA from normal skin and from peripheral blood of Kaposi's sarcoma-free heart transplant recipients. Samples were analyzed by polymerase chain reaction with specific primers to amplify the KS 330 sequence. RESULTS: The KS 330 fragment was found in Kaposi's sarcoma tissue of all three patients, in normal skin of one of them, and in peripheral blood of two. It was not detected in any of the samples from skin or peripheral blood of heart transplant recipients not affected by Kaposi's sarcoma. DNA extracted from a peripheral blood sample of one patient before transplantation showed that the KS 330 sequence was already detectable at that time. CONCLUSIONS: These findings suggest that Kaposi's sarcoma-associated herpesvirus may play a significant role in the pathogenesis of all forms of Kaposi's sarcoma. The development of the tumor in transplant recipients may be related, at least in some cases, to transplantation-associated immunosuppression, rather than to the acquisition of the virus from the donor.