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Abstract: Aim: Patients with heart failure (HF) have reduced exercise capacity. The beneficial effect of beta-blocker on prognosis is not matched by an impact on exercise capacity and quality of life. We performed a randomised open blinded endpoint study to assess the effect of heart rate reduction with carvedilol, ivabradine, and their combination on exercise capacity in HF patients receiving maximal dose of ACE inhibitor. Methods and results: After a run-in phase patients were randomly allocated to 3 groups: carvedilol up to 25mg bid (n=38); ivabradine up to 7.5mg bid (n=41); and carvedilol/ivabradine up to 12.5/7.5mg bid (n=42). The maximal dose of study treatment was more frequently tolerated in patients receiving ivabradine (36/41) than in those receiving carvedilol (18/38) or combination therapy (32/42) (P <0.01 ivabradine versus carvedilol). Heart rate was reduced in all three groups, but to a greater extent by the combination. The distance walked on the 6-min walking test and the exercise time on MVO2 test significantly improved in the ivabradine and combination groups (both P <0.01 versus baseline), as did peak VO2 and VAT (P <0.01 for ivabradine and P <0.03 for combination versus carvedilol, respectively). No changes in these parameters were found with carvedilol. The patients receiving ivabradine or the combination had better quality of life (P <0.01 versus baseline for ivabradine and P< 0.02 for combination), versus no change with carvedilol. Conclusion: Ivabradine alone or in combination with carvedilol is more effective than carvedilol alone at improving exercise tolerance and quality of life in HF patients. [Copyright &y& Elsevier]

Atrial fibrillation (AF) occurs frequently soon after coronary artery bypass grafting (CABG) and often results in increased mortality and morbidity, particularly in patients with heart failure. New-onset AF is also a common event in the early period after discharge from a cardiac surgery clinic. Current guidelines recommend β blockers as first-line medication for the prevention of AF after CABG. In this prospective study, we investigated the effectiveness of the highly selective β1 receptor antagonist bisoprolol compared to the less selective β blocker carvedilol in preventing postdischarge AF after CABG in patients with decreased left ventricular function. Three hundred twenty patients (231 men, 89 women, mean age 66 ± 10 years) with ejection fraction <40% who underwent CABG and were then referred to an in-hospital cardiac rehabilitation program were randomized to receive bisoprolol (n = 160) or carvedilol (n = 160) starting 4 to 5 days after surgery. Bisoprolol was started at 1.25 mg 1 time/day and carvedilol was started 3.125 mg 2 times/day. All patients underwent continuous telemetric electrocardiographic monitoring for 5 days after entry in the study and thereafter 2 times/day routinely up to hospital discharge. During follow-up, 23 patients (14.6%) in the bisoprolol group and 37 patients (23%) in the carvedilol group developed AF (relative risk 0.6, confidence interval 0.4 to 0.9, p = 0.032). Twenty-six percent of all AF episodes were asymptomatic. At the 4-week outpatient visit, those in the bisoprolol group showed a significantly greater decrease in heart rate, being in sinus rhythm or AF (−15.6 ± 3 vs −9.4 ± 3 beats/min, p = 0.021), whereas changes in systolic and diastolic blood pressures did not differ significantly. In conclusion, bisoprolol is more effective than carvedilol in decreasing the incidence of postdischarge AF after CABG in patients with decreased left ventricular function. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heart Rate Variability (HRV) and Baroreflex Sensitivity (BRS) are impaired in patients with Chronic Heart Failure (CHF) and carry negative prognosis. Exercise training improves these parameters. However, the relationship between exercise training with HRV and BRS has been investigated without regard for individual training loads. We tested the hypothesis that in CHF patients changes in HRV and BRS are dose–response related to individual volume/intensity training load (TL). Methods: Twenty patients with stable postinfarction CHF under optimal medical treatment were randomized to either aerobic continuous training (ACT) or aerobic interval training (AIT) for 12weeks. Individualized TL was monitored by the Training Impulses (TRIMPi) method, which was determined using the individual HR and lactate profiling determined during a treadmill test at baseline. HRV (standard deviation of mean R-R interval) and BRS were assessed at rest and 3weeks apart, throughout the study. Results: HRV, BRS and R–R interval increased significantly with training, being very highly correlated to the dose of exercise with a second-order regression model (r 2 ranged from 0.75 to 0.96; P<0.001), resembling a bell-shaped in the ACT, and an asymptotic-shaped curve in the AIT groups, respectively. These changes were accompanied by a significant increase in functional capacity. No significant differences were detected between ACT and AIT in any variable. Conclusions: These results suggest that improvements in HRV and BRS by exercise training in CHF patients are dose related to TL in a non-linear fashion on an individual basis, with optimal results at moderate doses of exercise. [Copyright &y& Elsevier]

Abstract: Objectives: We studied the effect of a short-term (3weeks) exercise training program on the number of circulating CD34/KDR+ endothelial progenitor cells (EPCs) and on serum levels of matrix metalloproteinases (MMPs) in chronic heart failure (CHF) patients as well as on serum capacity to foster colony forming units-endothelial cells (CFU-ECs) in vitro. Methods: Effectiveness of training was assessed by the 6-minute walking test (6MWT). Peripheral blood and serum were obtained from fourteen patients with CHF due to coronary artery disease before and after an inpatient aerobic exercise training program. At admission and at discharge we analysed circulating EPC number and serum levels of MMPs, TIMP-1 and TNF-α. The number and function of CFU-EC colonies were evaluated in cultures performed with serum obtained before and after training. Results: After training, distance walked at 6MWT and number of circulating CD34/KDR+ cells increased (from 154±27 to 233±48m; P <0.0001 and from 5±3 to 9±6 cells/ml P <0.05, respectively). Conversely, serum concentrations of MMP-1 and TIMP-1 decreased significantly (from 11.4±2.4 to 6.3±1.1ng/ml, and from 320.4±41.2 to 167.2±12.6ng/ml, respectively, both P <0.01), while MMP2/TIMP-1 and MMP-9/TIMP-1 ratios increased. Interestingly, we found increased CFU-EC proliferation in cultures performed with serum obtained after training. Conclusions: Considering that both EPCs and MMPs might play a role in vascular remodeling, the increased number of EPCs and MMP activities observed in this study, suggest that the selected short-term exercise training could be a potential therapeutic strategy to rescue cardiac function in CHF patients. [Copyright &y& Elsevier]