Predictors of improved left ventricular systolic function in an urban cardiomyopathy program.

After long-term therapy, some patients with systolic heart failure (HF) display improved left ventricular (LV) function over time, a response that is associated with improved long-term outcomes. To investigate predictors of improved LV function in an ethnically diverse HF cohort, we selected 71 patients with HF who had baseline ejection fractions (EF) <40%, follow-up EFs > or =50%, and >20% increases on follow-up echocardiography performed > or =6 months later. Their clinical features were compared with 142 age- and gender-matched control patients with baseline EFs <40% and no change or worse EFs on follow-up echocardiography. The baseline EFs were similar between patients and controls. Compared with controls, patients had a lower prevalence of diabetes mellitus (19.7% vs 36.6%, p = 0.01), a lower prevalence of an ischemic cause of disease (8.4% vs 35.2%, p <0.001), but a higher prevalence of a hypertensive cause of cardiomyopathy (29.6% vs 12%, p <0.001). Fewer patients than controls used aspirin (p = 0.04) or statins (p = 0.001) or had previous cardiac procedures (p = 0.009). In a multivariate conditional logistic regression model adjusting for age, gender, disease cause, statin use, cardiac procedures, change in heart rate, and follow-up time, hypertensive etiology was most strongly associated with improved LV function (adjusted odds ratio 9.73, 95% confidence interval 1.44 to 52.76, p = 0.02). In conclusion, patients with hypertensive causes of HF are more likely to demonstrate improved LV function over time than patients with ischemic causes of HF. Because long-term prognosis and indication for defibrillator implantation may be affected by changes in LV function, the present study provides additional support for the importance of evaluating the cause of HF to guide management.

Platelet-activating factor antagonists decrease follicular dendritic-cell stimulation of human B lymphocytes.

Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6 to 10-8 M) inhibited [3H]-thymidine incorporation by up to 35% +/- 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.