The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group.

OBJECTIVE: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. METHODS: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. RESULTS: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). CONCLUSION: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.

Discrepancy between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy.

A pretransplant diagnosis was compared with the diagnosis made after macroscopic and microscopic examination of the explanted hearts in 112 cardiac transplant recipients. A coronary angiogram was recorded in 87.5% and endomyocardial biopsy was performed in 12.5% of patients within 1 year of the transplant. Echocardiograms were obtained in all patients. Before transplantation, 57.1% of patients were classified as having ischemic cardiomyopathy and 33.9% were classified as having idiopathic dilated cardiomyopathy (IDC). At explantation, severe coronary artery disease was found in all patients with a pretransplant diagnosis of ischemic cardiomyopathy, in 9 patients with a pretransplant diagnosis of IDC (6 of them had a "normal" pretransplant angiograms), and in 3 of the 4 patients with presumptive alcoholic cardiomyopathy. Left ventricular hypertrophy, undetected on echocardiography, was found at autopsy in 11 patients with presumed IDC, and acute myocarditis was found in 3 patients with a pretransplant diagnosis of IDC. A correct pretransplant diagnosis can lead to different management (e.g., bypass surgery rather than transplant), and may also portend different pre- and post-transplant prognoses. The results of this study suggest that an "in-depth" search for a cause should be conducted in all patients with heart failure, regardless of their clinical presentation. Our study also emphasizes the limitations of coronary angiography and echocardiography in patients with IDC and the need for improving current diagnostic techniques in these patients.

South American Heart Transplantation Registry of patients receiving everolimus in their immunosuppressive regimens.

The increasing number of heart transplant recipients receiving immunosuppression with mammalian target of rapamycin inhibitors prompted the implementation of a South American Transplant Physicians Group to register these patients in a database. Everolimus (EVL) is a signal proliferation inhibition that reduces graft vascular disease when used de novo. Recently, its administration has expanded to subjects with resistant rejection or with side effects due to other immunosuppressive drugs (calcineurin inhibitors and/or steroids), allowing for better regulation of the immunosuppressive regimen. Herein we have shown the data collected from patients receiving EVL in ten South American Heart Transplant Centers. We have concluded that the administration of EVL is a useful adjunctive therapy that allows the reduction or suspension of other immunosuppressive drugs that caused unwanted side effects, without a loss of immunosuppressive efficacy, with manageable side effects, and constituting a valuable therapeutic option.

Immunohistochemical staining of lymphocytes for the reliable diagnosis of myocarditis in endomyocardial biopsies.

Interobserver variability in the interpretation of pathologic endomyocardial biopsies for detecting myocarditis has been widely reported. Thus, conflicting reports about the therapeutic benefit of immunosuppressive treatment in myocarditis may be due to differences in the interpretation of the biopsy findings. In doubtful cases, scattered interstitial cells may be present between myocytes and can be misinterpreted as true lymphocytes. In our study, a further characterization of interstitial cells in endomyocardial biopsies previously diagnosed as showing 'myocarditis' was performed by lymphocyte immunophenotyping with immunocytochemical techniques for membrane and cytoplasmic antigens. Common leukocyte antigen (CLA), kappa and lambda light immunoglobulin chains and T lymphocyte antigens were made visible by an indirect immunoperoxidase technique. A previous diagnosis of 'myocarditis' had been established histologically in 27 patients by the presence of an inflammatory cell infiltrate associated with focal acute cellular damage. These specimens were selected for further study using an immunoperoxidase technique. The number of negative and positive mononuclear cells for each marker was counted on all fields at a magnification of X 400. These numbers were correlated with the extent of interstitial fibrosis and/or myocyte damage on each sample. According to previous studies, 5.0 lymphocytes/high-power field were considered as the lower limit of myocarditis if they were associated with myocyte injury. From the 27 samples previously diagnosed histologically as 'myocarditis' only 14 showed 5 or more CLA-positive mononuclear cells/X 400 field. In 6 out of 8 selected cases having less than 5 CLA-positive cells, no T-antigen-positive cells could be detected. The remaining samples showed T lymphocytes localized in acute infiltrated areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA)

In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias. The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure. Our prospective multicentre trial included 516 patients on optimal standard treatment for heart failure. Patients were randomised to 300 mg/day amiodarone (260) or to standard treatment (256). Intention-to-treat analysis showed 87 deaths in the amiodarone group (33.5%) compared with 106 in the control group (41.4%) (risk reduction 28%; 95% CI 4%-45%; log rank test p = 0.024). There were reductions in both sudden death (risk reduction 27%; p = 0.16) and death due to progressive heart failure (risk reduction 23%; p = 0.16). Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure (119 versus 149 in the control group; risk reduction 31%; 95% CI 13-46%; p = 0.0024). The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia. Side-effects were reported in 17 patients (6.1%); amiodarone was withdrawn in 12. Low-dose amiodarone proved to be an effective and reliable treatment, reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias.