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Objectives: We sought to compare the short- and long-term clinical effects of atrial synchronous pre-excitation of one (univentricular) or both ventricles (biventricular), that provide cardiac resynchronization therapy (CRT)., Background: In patients with heart failure (HF) who have a ventricular conduction delay, CRT improves systolic hemodynamic function. The clinical benefit of CRT is still being investigated., Methods: Forty-one patients were randomized to four weeks of first treatment with biventricular or univentricular stimulation, followed by four weeks without treatment, and then four weeks of a second treatment with the opposite stimulation. The best CRT stimulation was continued for nine months. Cardiac resynchronization therapy was optimized by hemodynamic testing at implantation. The primary end points were exercise capacity measures. Data were analyzed by two-way repeated-measures analysis of variance., Results: The left ventricle was selected for univentricular pacing in 36 patients. The clinical effects of univentricular and biventricular CRT were not significantly different. The results of each method were pooled to assess sequential treatment effects. Oxygen uptake during bicycle exercise increased from 9.48 to 10.4 ml/kg/min at the anaerobic threshold (p = 0.03) and from 12.5 to 14.3 ml/kg/min at peak exercise (p < 0.001) with the first treatment, and from 10.0 to 10.7 ml/kg/min at the anaerobic threshold (p = 0.2) and from 13.4 to 15.2 ml/kg/min at peak exercise (p = 0.002) with the second treatment. The 6-min walk distance increased from 342 m at baseline to 386 m after the first treatment (p < 0.001) and to 416 m after the second treatment (p = 0.03). All improvements persisted after 12 months of therapy., Conclusions: Cardiac resynchronization therapy produces a long-term improvement in the clinical symptoms of patients with HF who have a ventricular conduction delay. The differences between optimized biventricular and univentricular therapy appear to be small for short-term treatment.

Objectives: We sought to study exercise capacity at different points in time after left ventricular assist device (LVAD) implantation and subsequent heart transplantation (HTx)., Background: The lack of donor organs warrants alternatives for transplantation., Methods: Repeat treadmill testing with respiratory gas analysis was performed in 15 men with a LVAD. Four groups of data are presented. In group A (n = 10), the exercise capacities at 8 weeks and 12 weeks after LVAD implantation were compared. In group B (n = 15), the data at 12 weeks are presented in more detail. In group C (n = 9), sequential analysis of exercise capacity was performed at 12 weeks after LVAD implantation and at 12 weeks and one year after HTx. In group D, exercise performance one year after HTx in patients with (n = 10) and without (n = 20) a previous assist device was compared., Results: In group A, peak oxygen consumption (Vo2) increased from 21.3+/-3.8 to 24.2+/-4.8 ml/kg body weight per min (p < 0.003), accompanied by a decrease in peak minute ventilation/ carbon dioxide production (VE/Vco2) (39.4+/-10.1 to 36.3+/-8.2; p < 0.03). In group B, peak Vo2 12 weeks after LVAD implantation was 23.0+/-4.4 ml/kg per min. In group C, levels of peak Vo2 12 weeks after LVAD implantation and 12 weeks and one year after HTx were comparable (22.8+/-5.3, 24.6+/-3.3 and 26.2+/-3.8 ml/kg per min, respectively; p = NS). In group D, there appeared to be no difference in percent predicted peak Vo2 in patients with or without a previous LVAD (68+/-13% vs. 74+/-15%; p < 0.37), although, because of the small numbers, the power of this comparison is limited (0.45 to detect a difference of 10%)., Conclusions: Exercise capacity in patients with a LVAD increases over time; 12 weeks after LVAD implantation, Vo2 is comparable to that at 12 weeks and one year after HTx. Previous LVAD implantation does not seem to adversely affect exercise capacity after HTx.

It is unclear whether the intracardial immune reactivity after heart transplantation influences the peripheral immunological status (activation or nonresponsiveness) of the patient. Co-stimulation and activation-induced cell death (AICD) or apoptosis play an important role in determining the balance between lymphocyte reactivity and nonreactivity. Therefore, we studied the expression of co-stimulatory molecules and the process of apoptosis in biopsies of human heart allografts, using immunohistochemistry. Although a normal expression of co-stimulatory molecules on antigen-presenting cells was observed, the expression of their counter-structures on T cells was absent. This may be due to chronic T cell activation, which can lead to the induction of apoptosis via the Fas/Fas ligand pathway. In the infiltrates, a considerable percentage of the lymphocytes, but not the macrophages, were apoptotic. Apoptosis was confirmed by DNA fragmentation analysis. Increased numbers of Bax-expressing versus decreased numbers of Bcl2-expressing lymphocytes in comparison with normal lymphoid tissue confirmed a imbalance in favor of apoptosis. Apoptosis was biased towards CD4+ T cells (65.7% versus 26.6% in CD8+ T cells). Fas was expressed on most of the infiltrating cells. Fas ligand expression was also observed, not only on most of the T cells but also on all macrophages. Because macrophages were often detected in close contact with T cells, they may play a role in T cell regulation via the Fas/Fas ligand pathway. This study indicates that, during rejection, not only is tissue damage induced by infiltrating T cells, but also the infiltrating lymphocytes themselves are actively down-regulated (eg, AICD) by one another and by macrophages in the infiltrate. This regulatory process may affect the immunological status of the patient after heart transplantation.