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%).

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

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.

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.

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.

Current induction immunosuppression and post-heart transplant lymphoproliferative disorders.

BACKGROUND: The use of high-dose OKT3 has been reported to be associated with a high incidence of posttransplant lymphoproliferative disorders (PTLD) in heart transplantation (HTx) recipients. The incidence and characteristics of PTLD with current induction protocols remain largely unknown. The aim of our study was to analyze the incidence and characteristics of PTLD in a large series of HTx recipients treated with low-dose OKT3 induction. METHODS: From 1984 to 2002, a retrospective review of diagnosis, treatment, and evolution of PTLD cases was performed on the 560 patients who underwent HTx in our center. RESULTS: The incidence of PTLD was 1% (6/560). The disease occurred early after HTx in two cases and between 13 and 121 months in the other four. Molecular studies showed evidence of Epstein-Barr virus (EBV) infection in four patients. B-cell proliferation was observed in five cases, and T-cell proliferation in the other one. Various therapies were employed for each patient. Ganciclovir and reduction in immunosuppression were the most common measures. Interestingly, OKT3 was used as a specific anti-T-cell proliferation agent with some success in the one case of T-cell PTLD. Complete remission was achieved in just two patients, whereas the other four (67%) died, mostly due to other conditions. CONCLUSIONS: The use of low-dose OKT3 as induction therapy did not increase the incidence of PTLD in our series. Late appearance of disease prevailed among our patients. Despite a multidisciplinary approach to therapy, including the use of OKT3 against T-cell proliferation, the mortality rate was high (67%).

[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.

Three cases of tuberculosis after heart transplantation in Spain.

Three cases are presented of tuberculosis occurring in a series of 410 heart transplant recipients in a Spanish hospital, representing a rate of 0.73%. Twenty-eight cases reported in the literature are also reviewed. In most series reported, tuberculosis occurred in a small percentage of heart transplant recipients, the average rate being 1.25%. Compared to the general population, a higher percentage (28%) of extrapulmonary and disseminated forms of the disease is seen in these patients. Although a cure without recurrence can usually be achieved with a conventional anti-tuberculous antibiotic regimen, the disease is still associated with a significant mortality rate of 11%. Guidelines for the early diagnosis and treatment of these patients are discussed.

VDD pacing with single lead in a heart transplant recipient: case report.

Permanent pacemaker implantation is required in a large number of transplantation patients principally because of sinus node dysfunction of the donor atrium. The most suitable mode of pacing in these cases is still subject to controversy. We describe one case of a single lead system of VDD stimulation and sensing of the recipient atrial signal in a 32-year-old patient with posttransplant symptomatic sinus node dysfunction. Physiological adaptation of rate was achieved with recovery of normal receptor sinus node function.

Mitral valve replacement in a heart transplant recipient with iatrogenic mitral regurgitation.

A 65-year-old cardiac transplant recipient suffered rupture of the mitral valve apparatus during endomyocardial biopsy of the left ventricle. Severe mitral regurgitation resulted, and because of heart failure with progressive clinical deterioration the patient was finally subjected to mitral valve replacement. He had a favorable postoperative course and is now asymptomatic.

[A heart transplant in a patient with doxorubicin-induced myocardiopathy as a complication of the treatment of a lymphoma]. / Trasplante cardíaco en un paciente con miocardiopatía por doxorrubicina como complicación del tratamiento de un linfoma.

We present the case of a young man who developed severe cardiomyopathy eight years after receiving high-dose doxorubicin therapy as treatment for diffuse lymphoblastic lymphoma. He underwent cardiac transplantation and eighteen months later the tumor has not recurred and the patient has no cardiac symptoms.

Rhodococcus equi: first case in a heart transplant recipient.

Rhodococcus equi is a gram-positive diphtheroid that occasionally affects immunocompromised patients, usually causing a chronic respiratory infection with cavitating pulmonary opacities on chest radiograph that resemble mycobacterial or fungal disease. Etiologic diagnosis presents a number of pitfalls, because Rhodococcus equi isolates mimic many of the characteristics of other microorganisms more familiar to the laboratory staff. The treatment of choice for this disease has not yet been established, and its mortality rate is greater than 50% in individuals with human immunodeficiency virus and 20% to 25% among the remaining patients. We describe here the first case of Rhodococcus equi infection in a heart transplant recipient. Clinical presentation was typical, and treatment with a sensitivity-based combination of antibiotics resulted in resolution of both the clinical and radiologic picture.

Heart transplantation in a patient with liver hydatidosis.

The human can serve as an accidental intermediate host to Echinococcus granulosus, a parasite that targets dogs as its definitive hosts. We present the case of a 27-year-old man with liver hydatidosis, who underwent heart transplantation because of ischemic cardiomyopathy. The immunosuppressor treatment had no effect on the size of the cysts, which were removed surgically 14 months after heart transplantation; good results persist after 3 years of follow-up.