Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure. / Documento de consenso de la Sociedad Española de Cardiología y la Sociedad Española de Medicina Interna sobre el diagnóstico y tratamiento del déficit de hierro en la insuficiencia cardíaca.

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure.

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.

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.

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%).