Progression and management of chronic heart failure.

Current heart failure therapeutic guidelines are based on a new classification of the progression of the syndrome of chronic heart failure (CHF) that was proposed by ad hoc committees of the American College of Cardiology (ACC) and the American Heart Association (AHA). The new ACC/AHA classification depicts the progression of CHF in 4 stages that are labeled A to D. The 4 stages range from risk factors for CHF (A) to the presence of structural heart disease (B) and the development of symptoms (C). The last stage (D) is one of low cardiac output state despite optimal medical therapy. The merit of this new classification is to encourage tailoring of CHF therapy according to the stage of the syndrome. However, except for the final stage D that has clear therapeutic implications, the first 3 stages A, B and C do not have clear therapeutic implications. Moreover, these first 3 stages may inadvertently delay the diagnosis of CHF and fail to identify the important therapeutic target at each stage of CHF. A revised classification consisting of only 3 stages is proposed. These 3 stages are: 1) Left ventricular (LV) remodeling; 2) clinical heart failure and 3) low cardiac output state. These 3 stages have the advantage of delineating precise therapeutic targets at each stage thereby facilitating the management of patients with CHF by non-experts in the field.

Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation.

Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels. In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.

Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus.

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied. At baseline, history, clinical and laboratory evaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 +/- 1.53 years. After a mean period of 5.39 +/- 1.42 years; 40 patients underwent a repeat TTE. Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients. During follow-up, ICVAs had recurred in seven patients, while a first event TIA occurred in one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstrates that LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.

Bone marrow transplantation in the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is an uncommon, progressive, sometimes lethal fibrotic disease whose pathogenesis probably includes immunologic elements, especially early in its course. There is no proven therapy for this disease, although some promising results have been obtained with the use of immunosuppressive drugs such as cyclophosphamide. There exists a subgroup of patients who have rapidly progressive disease or who are not responsive to conventional treatment, and who may benefit from intensive immunosuppression with stem cell rescue (stem cell transplantation). The rationale for bone marrow transplantation (BMT), and, more recently, peripheral blood stem cell transplantation (SCT), has been validated by studies on animal models of autoimmunity. Autologous transplantation has shown encouraging anecdotal results, and it is now being evaluated in phase I/II studies in patients with predictably poor outcome. In this light, reliably identifying patients early in the course of SSc is extremely important in order to establish correct eligibility criteria. For patients unable to tolerate transplant regimens, other approaches may be feasible. In this regard, nonmyeloablative approaches, such as immunosuppression without rescue and mixed chimerism, are also discussed.