Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation

PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8%) presented a good response. The response rate for the different indications was: (1) acute cellular + sepsis - 0/1 case; (2) recurrent acute cellular - 1/1 case; (3) OKT3-resistant acute cellular - 2/2 cases; (4) steroid-resistant acute cellular + active viral infection - 3/3 cases; (5) chronic rejection - 8/11 cases (72.7% response rate). The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.

Histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics: a review

PURPOSE: To review the medical literature regarding the histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics. METHODS: Review of articles in the MEDLINE and LILACS databases regarding serum levels and prevalence of alterations in aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, and total bilirubin, in relation to liver histopathology, with or without discrimination of types of histopathologic alteration. RESULTS: Global mean prevalence rates of aspartate-aminotransferase and alanine-aminotransferase alterations were 86.3% and 51.1%; in cases with steatosis they were 79.1% and 38.5%; and in cases of hepatitis, 90.1% and 58%. In all studies, prevalence rates of aspartate-aminotransferase alterations were significantly higher with lower variability than those of alanine-aminotransferase. Mean aspartate-aminotransferase levels were higher than 2N (N is the upper normal limit of the method employed) in all cases with hepatitis histopathology, while those of alanine-aminotransferase were 1.48N, in the same cases. Prevalence of alkaline phosphatase and total bilirubin abnormalities were 74.5% and 74.9% globally; in cases of steatosis, they were 70.9% and 67.9%; and in cases of hepatitis, 75.9% and 77.7%. Mean alkaline phosphatase levels were above the upper normal limit in all cases, but those of total bilirubin were above normal in 4 of 7 hepatitis studies. CONCLUSIONS: Prevalence of aspartate-aminotransferase alteration was consistently related to presence of histopathologic abnormalities; an enzyme level higher than 2N suggests the diagnosis of alcoholic hepatitis.

A questionnaire to evaluate the impact of chronic diseases: validated translation and Illness Effects Questionnaire (IEQ) reliability study

INTRODUCTION: Patients' perception about their health condition, mainly involving chronic diseases, has been investigated in many studies and it has been associated to depression, compliance with the treatment, quality of life and prognosis. The Illness Effects Questionnaire (IEQ) is a tool which makes the standardized evaluation of patients' perception about their illness possible, so that it is brief and accessible to the different clinical settings. This work aims to begin the transcultural adaptation of the IEQ to Brazil through the validated translation and the reliability study. METHODS: The back-translation method and the test-retest reliability study were used in a sample of 30 adult patients under chronic hemodialysis. The reliability indexes were estimated using the Pearson, Spearman, Weighted Kappa and Cronbach's alpha coefficients. RESULTS: The semantic equivalence was reached through the validated translation. In this study, the reliability indexes obtained were respectively: 0.85 and 0.75 (p < 0.001); 0.68 and 0.92 (p < 0.0001). DISCUSSION: The reliability indexes obtained attest to the stability of responses in both evaluations. Additional procedures are necessary for the transcultural adaptation of the IEQ to be complete. CONCLUSION: The results indicate the translation validity and the reliability of the Brazilian version of the IEQ for the sample studied.

Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML) in patients with dilated cardiomyopathy (DCM) and New York Heart Association (NYHA) class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO) and cardiac index (CI); pulmonary capillary wedge pressure (PCWP); mean aortic pressure (MAP); mean pulmonary artery pressure (MPAP); mean right atrial pressure (MRAP); left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively); peak rate of left ventricular pressure rise (dP/dt); systemic vascular resistance (SVR); pulmonary vascular resistance (PVR); and heart rate (HR). RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt) and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

Evaluation of the heart rate and arrhythmias following the Maze procedure for chronic atrial fibrillation

PURPOSE: To assess the presence and the prevalence of arrhythmias and the variability of the heart rate in the medium-term postoperative period following the maze procedure for chronic atrial fibrillation (AF). METHODS: Seventeen patients with a mean age of 51.7±12.9 years, who previously underwent the maze procedure without cryoablation for chronic atrial fibrillation, were evaluated with the 24 hour electrocardiogram (ECG) - Holter monitoring from the 6th month after the operation. Valvular and coronary procedures were concomitantly performed. RESULTS: The mean heart rate during Holter monitoring was 82±8bpm; the maximal heart rate was 126 ± 23bpm and the minimal heart rate 57±7bpm. Sinus rhythm was found in 10 (59%) patients and atrial rhythm was found in 7 (41%). Supraventricular extrasystoles had a rate of 2.3±5.5% of the total number of heartbeats and occurred in 16 (94%) patients. Six (35%) patients showed nonsustained atrial tachycardia. Ventricular extrasystoles, with a rate of 0.8±0.5% of the total heartbeats, occurred in 14 (82%) patients. The chronotropic competence was normal in 9 (53%) patients and attenuated in 8 (47%). The atrioventricular conduction (AV) was unchanged in 13 (76%) patients and there were 4 (24%) cases of first degree atrioventricular block (AVB). CONCLUSION: After the maze procedure, the values for the mean heart rate, AV conduction and chronotropic competence approach the normal range, although some cases show attenuation of the chronotropic response, first degree AV block or benign arrhythmias.

Natural course of subsequent pregnancy after peripartum cardiomyopathy

OBJECTIVE: To assess the effect of subsequent pregnancy after peripartum cardiomyopathy (PPCM) on maternal and fetal outcome. METHODS: Prospective study of 34 patients with the diagnosis of PPCM (mean age= 26years). At the time of first diagnosis 5 were in NYHA functional class (FC) II for heart failure, one in FC III and 28 in FC IV. After clinical treatment, patients were advised to avoid new pregnancies and a follow-up was obtained. RESULTS: There were 12 (35.3%) subsequent pregnancies in patients (pt) aged 19 to 44 years (mean 32), divided into two groups: GI: 6 pts who had normalized their heart size and GII: 6 pts with persistent cardiomegaly. GI had initially mild clinical manifestations ( 3 were in FC II, 1 in FC II and 2 in FC IV) and complete recovery of cardiac function (FC I). A new pregnancy was well-tolerated in 5 (83.3%); 1 pt presented with preeclampsia, and progressed to FC II. Presently, 5 pt are in FC I and 1 in FC II. GII pts had more severe heart failure at the onset of PPCM (1 pt in FC II and 5 in FC IV); during follow-up, 4 pt were in FC I and 2 in FC II. A new pregnancy was well tolerated in all of them, but the eldest, who had had 2 pregnancies and had a progressive worsening of clinical status, dying 8 years after the last pregnancy and 13 years after the diagnosis of PPCM. The remaining 5 pt are still alive, 3 in FC I and 2 in FC II, with worsening of FC in 1. Subsequent pregnancies occurred 3-7 years after clinical treatment of PPCM and no fetal distress was observed. CONCLUSION: Subsequent pregnancies are well-tolerated after PPCM, but not devoid of risk. No fetal distress was observed. A minimum interval of 3 years after the recovery of function seems to be safe for subsequent pregnancies.

Results of the surgical treatment of chronic atrial fibrillation

OBJECTIVE: Report clinical experience in surgical treatment of atrial fibrillation (AF) by Cox-maze procedure. METHODS: 61 patients underwent surgical treatment for AF. Two had primary AF and 59 AF secondary to heart disease (2 atrial septal defects, 57 mitral). Ages ranged from 20 to 74 years (mean = 49). There were 44 females (72%). The surgical technique employed was Cox 3 without cryoablation. The patients were follow-up in specific at patient clinics and underwent periodical ECG, exercise tests, echocardiogram and Holter monitoring. RESULTS: In-hospital mortality was 4.9% and late mortality 1.6%. A temporary pacemaker was used in 28 (46%) and a definitive in 7 patients (11.4%). On hospital discharge, AF remained in 17%; 63.9% had sinus rhythm, 6.9% atrial rhythm, 1.7% junctional rhythm, and 10.3% had pacemaker rhythm. In the last evaluation, AF was present in 19.5%; (70.5% sinus rhythm, 4% atrial rhythm, 2% atrial tachycardia, and 4% pacemaker rhythm). There was no report of thromboembolic episodes. Chronotropic response was considered adequate in 19%, intermediate in 29%, and inadequate in 42%. In Holter monitoring, the mean heart rate was 82±8 bpm, with a minimum of 57±7 bpm and maximum of 126±23 bpm, with supraventricular extrasystoles in 2.3±5.5% of the total heartbeats and ventricular extrasystoles in 0.8±0.5%. In the echocardiogram, the A wave was present in the left atrium in 87.5%. CONCLUSION: Maze procedure is effective and has acceptable surgical risk. Atrial or sinus rhythms remain stable with a small but remarkable frequency of atrial and ventricular arrhythmias. Left atrial contraction is present, although attenuated, as well as the chronotropic response to exercise.

Cardiac abnormalities in the acquired immunodeficiency syndrome. A prospective study with a clinical-pathological correlation in twenty-one adult patients

OBJECTIVE - To evaluate the cardiac abnormalities and their evolution during the course of the acquired immunodeficiency syndrome, as well as to correlate clinical and pathological data. METHODS - Twenty-one patients, admitted to the hospital with the diagnosis of acquired immunodeficiency syndrome, were prospectively studied and followed until their death. Age ranged from 19 to 42 years (17 males). ECG and echocardiogram were also obtained every six months. After death, macro- and microscopic examinations were also performed. RESULTS - The most frequent causes of referral to the hospital were: diarrhea or repeated pneumonias, tuberculosis, toxoplasmosis or Kaposi sarcoma. The most frequent findings were acute or chronic pericarditis (42%) and dilated cardiomyopathy (19%). Four patients died of cardiac problems: infective endocarditis, pericarditis with pericardial effusion, bacterial myocarditis and infection by Toxoplasma gondii. CONCLUSION - Severe cardiac abnormalities were the cause of death in some patients. In the majority of the patients, a good correlation existed between clinical and anatomical-pathological data. Cardiac evaluation was important to detect early manifestations and treat them accordingly, even in asymptomatic patients.

A new surgical approach for treating dilated cardiomyopathy with mitral regurgitation

OBJECTIVE: To evaluate the early outcome of mitral valve prostheses implantation and left ventricular remodeling in 23 patients with end-stage cardiomyopathy and secondary mitral regurgitation (NYHA class III and IV). METHODS: Mitral valvular prosthesis implantation with preservation of papillary muscles and chordae tendinae, and plasty of anteriun cuspid for remodeling of the left ventricle. RESULTS: The surgery was performed in 23 patients, preoperative ejection fraction (echocardiography) varied from 13% to 44% (median: 30%). In 13 patients associated procedures were performed: myocardial revascularization (9), left ventricle plicature repair (3) and aortic prosthese implantation (1). Early deaths (2) occurred on the 4th PO day (cardiogenic shock) and on the 20th PO day (upper gastrointestinal bleeding), and a late death in the second month PO (ventricular arrhythmia). Improvement occurred in NYHA class in 82.6% of the patients (P<0.0001), with a survival rate of 86.9% (mean of 8.9 months of follow-up). CONCLUSION: This technique offers a promising therapeutic alternative for the treatment of patients in refractory heart failure with cardiomyopathy and secondary mitral regurgitation.

Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study)

OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women) with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years), and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016) as well as an increase in left ventricular shortening fraction (p=0.02) and in left ventricular ejection fraction (p=0.017) occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

Peripheral arterial embolism. Report of hospitalized cases

OBJECTIVE: We analyzed the frequency of peripheral embolisms, the underlying heart disease,triggering factors, the sites of the emboli, and evolution of the patients. METHODS: We analyzed 29 cases of peripheral arterial embolism out of a total of 20,211 hospitalizations in a cardiology center in the city of São Paulo. The age was 51.89±18.66 years, and 15 were males. RESULTS: Embolism in the right lower limb occurred in 18 patients (62.0%),in the left lower 11(37.9%) and right upper 3 (10.3%) limbs, and in the left arm (1). Four patients had embolism in two limbs. The heart disease, mitral valvar heart disease (9 patients - 31.0%); infective endocarditis (7- 24.1%); dilated cardiomyopathy (6 - 20.6%); ischemic coronary heart disease (6 patients - 20.6%); and one patient with cor pulmonale. Atrial fibrillation was observed in 20 patients (68.9%), chronic in 12 patients (41.3% ) and acute in 8 (27.5%). All patients with mitral valvar heart disease had atrial fibrillation, chronic in 8 patients (88.8%); patients with cardiomyopathy and coronary heart disease, 4 in each group had atrial fibrillation, acute in 60% of the patients.Patients with infective endocarditis, 3 had staphylococcus and 2 Gram-negative bacteria. In the follow-up, 2 patients (6.8%) required limbs amputation, and 5 (17.2%) died due to embolism. CONCLUSION: Most of the time, embolism does not cause permanent complications. Our data highlight the importance of anticoagulation for patients acute atrial fibrillation in myocardial dysfunction and for patients with chronic atrial fibrillation in cases of mitral valvar heart disease to prevent peripheral embolism.