New strategies of cyclosporine monitoring in heart transplantation: initial results.

The aim of this study was to evaluate cyclosporine (CyA) absorption profiles in heart transplantation to establish the most adequate monitoring strategy and determine the optimal therapeutic range for AUC(0-4) or C2 levels. A total of 22 full pharmacokinetic studies were performed at steady-state in 22 adult heart transplant recipients (18 men, 4 women). Twelve studies were performed during the first month posttransplant (group I), and 10 studies were done after 1 month (group II). In 9 outpatients we performed an abbreviated AUC(0-4). The mean age of the patients was 49+/-15 years (range, 15-72 years), and the mean weight was 70.4+/-10.8 kg (mean, 54-98 kg). The CyA dosage had been adjusted to maintain trough levels (C0) in the putative target ranges of 200 to 400 ng/mL in group I and between 100 to 300 ng/mL in group II. Blood samples were drawn prior to and at 0.5, 1, 2, 4, 6, 8, and 12 hours after the morning dose. The CyA blood levels were measured by the AxSYM cyclosporine assay. The AUC was calculated by the trapezoidal rule. Multiple linear regression was done to evaluate the predictive ability of various limited sampling strategies. The C0 correlated poorly, either with the full AUC (r2=0.64) or the AUC(0-4) (r2=0.43), while C2 seemed to be the most accurate single predictor of drug exposure (r2=0.92 for AUC(0-12); r2=0.74 for AUC(0-4)). For both AUC(0-4) and AUC(0-12), all 2- or 3-point strategies had r2 values approaching that of the C2 value. In conclusion, C2 is a simple, fast, and accurate value to predict AUC(0-4) in routine clinical practice. Its implementation must focus on ensuring the commitment of all unit staff, thus ensuring that patients are sampled on time and minimizing the impact on workload.

[Clinical features and prognosis of infective endocarditis in the elderly]. / Características clínicas y pronósticas de la endocarditis infecciosa en el anciano.

INTRODUCTION AND OBJECTIVES: In recent decades the mean age of patients with infective endocarditis has progressively increased. The objective of the present study was to describe the clinical features and prognoses of infective endocarditis in the elderly. METHODS: A prospective study was performed of 125 non drug abuser patients over the age of 14 years and admitted from 1987 until 1997 in a single institution. Twenty-one patients were older than 65 years. RESULTS: No significant differences were observed among the age groups with respect to delay in diagnosis, clinical signs, site of the infection and the rate of negative blood cultures. Prosthetic valve endocarditis was more frequent in elderly than in younger adults (41 and 33%, respectively). S. viridans and enterococcus were more frequent (47 compared with 29% in younger adults, p < 0.05). Elderly patients underwent surgery less frequently (46 versus 56%) and most surgery was performed on an emergency basis. The in hospital mortality was higher in the elderly (50 versus 15%), p < 0.05. CONCLUSIONS: Prosthetic valve endocarditis and severe complications during the active phase are more frequent in the elderly and this is related to a worse prognosis in the short and intermediate term. A higher rate of elective surgery during the active phase could improve the prognosis of infective endocarditis in the elderly.

[Short and long-term prognosis of prosthetic valve endocarditis in non-drug addicts]. / Pronóstico a corto y largo plazo de la endocarditis sobre prótesis en pacientes no drogadictos.

INTRODUCTION AND OBJECTIVES: Prosthetic valve infective endocarditis is a complication of valvular replacement surgery with a high morbimortality during the in-hospital phase and an important risk of complications during follow-up. The objective of the present study is to assess the clinical features and the short and long-term prognosis of this disease. PATIENTS AND METHODS: A prospective study of 43 consecutive cases of prosthetic valve endocarditis in non-addict patients from January 1987 to March 1997. RESULTS: The mean age was 51 +/-16 years. Eight patients (19%) had early prosthetic valve endocarditis (two months following heart surgery), fourteen patients (32%) had intermediate (between 2 and 12 months post surgery) and twenty-one (49%) had late prosthetic valve endocarditis (more than one year after heart surgery). Transesophageal echocardiography was performed in 32 patients with a sensibility of 81%. Complications occurred in 86% of patients and 53% of patients underwent surgery during the active phase (25% was emergency surgery). Inpatient mortality was 23% (50% in early prosthetic valve endocarditis). After a mean follow-up of 56 months there were 5 cases of recurrence, four patients required late surgery and 5 patients died. Survival (excluding early mortality) was 82% at 5 years with no significant differences among patients who received only medical treatment and those who underwent surgery in the active phase. CONCLUSIONS: Early mortality of prosthetic valve endocarditis is, according to our experience of 20%. The prognosis of survivors to the active phase is favourable in the majority. Early prosthetic valve endocarditis still causes a high mortality rate despite the use of combined medical surgical treatment in most cases.

[The general characteristics and short- and long-term results of infective endocarditis in non-drug addicts]. / Características generales y resultados a corto y largo plazo de la endocarditis infecciosa en pacientes no drogadictos.

INTRODUCTION AND OBJECTIVES: Infective endocarditis is a disease with a high morbimortality during the active phase and a considerable risk of complications during follow-up. The aim of our study is to describe the clinical and prognostic features of infective endocarditis in non-drug addict patients in short and long terms. PATIENTS AND METHODS: A prospective study of 138 cases of infective endocarditis in non-drug addict patients through the parenteral pathway treated in our institution from 1987 to 1997. RESULTS: The mean age was 44 +/- 20 years. Ninety-five patients (69%) had native valve infective endocarditis and forty-three (31%) had prosthetic valve endocarditis. Streptococci were the causal microorganism in 34% and staphylococci in 33%. 83% of patients developed some type of complications during hospital stay. 51% of patients were operated on during the active phase (22% were urgent). The in-hospital mortality rate was 21%. 10 patients (9%) needed late cardiac surgery and seven patients (5%) died during follow-up. Global survival at 10 years was 71%. There were no statistical differences in survival in as much as the type of treatment received during the hospital stay in the active phase (medical alone or combined medical-surgical). CONCLUSIONS: A high early surgery rate in the active phase related to good long-term results and does not increase early in-hospital mortality. Medical treatment also offers good long-term results in cases of infectious endocarditis with absence of bad prognostic factors and good clinical outcome.

[Embolism in the right heart chambers: the diagnostic and therapeutic aspects]. / Embolia en cavidades cardiacas derechas: aspectos diagnósticos y terapéuticos.

Deep venus thrombosis may result in pulmonary embolism. In rare instances, embolization has occurred, not directly to the pulmonary arterial tree, but to the right heart chambers. Although the value of echocardiography in the diagnosis is well recognised, their is no consensus for the appropriate treatment. We report herein six cases of floating right atrial thrombi, diagnosed by echocardiography, in patients with pulmonary embolism, or unexplained shock or syncope. Surgical embolectomy was carried out in 4 patients, and thrombolytic therapy in 2, without in-hospital mortality. The high mortality associated to this entity may be improved by rapid echocardiographic recognition and emergency treatment with thrombolysis or surgery. Our data suggest the possible use of thrombolysis as a first-choice therapy in selected patients.

[Revascularization versus transplantation in patients with limited ejection fraction]. / Revascularización frente a trasplante en pacientes con fracción de eyección límite.

Ventricular dysfunction caused by ischemia is frequently a consequence of episodes of myocardial infarction which occur in the context of coronary disease, as well as of the ischemic situation in patients with severe failure in the main coronary arteries. The physiopathological mechanisms, as well as the therapeutic possibilities, are different in the case of diagnosed necrosis of myocardium or in situations of its circulatory deficiency, and, in the latter case, they depend on the period of absence of blood flow to the ischemic area, and on the occurrence of reperfusion of the area at the end of the ischemic event, the existence of an adequate collateral flow, etc. Classically, moderate degrees of ischemic ventricular dysfunction were considered as a preferential indication for revascularization surgery, together with the existence of coronary disease anatomically suitable for bypass. However, severe degrees of ventricular dysfunction were regarded as a contraindication to surgery, as they were considered irreversible due to an ischemic myocardiopathy which could not be palliated by an ulterior revascularization. These patients were referred to heart transplantation or to medical treatment when they did not fulfill the criteria to be included in transplantation programmes. In a later stage, due to a scarcity of donors for transplantation and to the disappointing results of pharmacological treatment in these patients, revascularization operations begun to be performed on patients with severe heart failure. Although initial results were not comparable to the ones obtained nowadays, work continued on this track and rapid improvement was achieved when particular clinical and diagnostic patterns were followed. Thus the concept of myocardial viability was created, presently being a central criterion in deciding which patients should go through revascularization. There are different methods to assess viability, and new ones are added to the diagnostic arsenal every day. With an adequate assessment of this concept, it is presently possible to really predict which patients may obtain clinical and functional improvement from their coronary disease in spite of severe deterioration of their cardiac function. This article analyzes the physiopathology of ventricular dysfunction, present methods to detect the viability of myocardial cells, as well as present indications and results obtained with ventricular revascularization in patients with severe depression of ventricular function as an alternative, currently well established, to heart transplantation.

[A comparison of bezafibrate and lovastatin treatment at the usual doses in post-heart transplant hyperlipemia]. / Comparación del tratamiento con bezafibrato y lovastatina a dosis habituales en la hiperlipemia postrasplante cardíaco.

INTRODUCTION: Coronary artery disease is a major limiting factor for long-term survival after heart transplantation. Hyperlipidemia is a probable risk factor for coronary artery disease in this kind of patient. Bezafibrate and lovastatin have proved to be effective in lowering total and low density lipoprotein cholesterol. The present study tested the safety and efficacy of both drugs on lipid levels in 21 patients with post-heart transplantation hyperlipidemia. PATIENTS AND METHODS: Patients maintained the same diet for three months. Then, they were randomized to lovastatin (20 mg/day) or bezafibrate (400 mg/day) for 8 weeks, and then, crossovered to an additional 8 weeks of bezafibrate or lovastatin. RESULTS: Both drugs were effective in lowering total and low density lipoprotein cholesterol and apoprotein B concentrations, but the effect of lovastatin was significantly greater. Only bezafibrate produced a significant reduction in total triglycerides and a significant rise in high density lipoprotein cholesterol and apoprotein AI. The total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios were decreased under both treatments. CONCLUSION: Both drugs, bezafibrate and lovastatin appear to be safe, effective and well-tolerated therapies for hyperlipidemia in cardiac transplant recipients.