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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]

Abstract: Aims: To evaluate whether metabolic syndrome MS has a gender dependent effect on the recovery of functional capacity in patients (pts) with coronary heart disease (CHD) undergoing a cardiac rehabilitation program. Methods and Results: We studied 286 CHD patients, age 66.2±10.6 (median±SD); M/F 187/99. Patients were divided into two groups according to the presence (MS, 48%) or not (nMS, 52%) of MS. MS was present in 48% of patients. Functional capacity was assessed by the distance walked at six minute walking test (6MWT), and by a maximal exercise test. Compared to patients without MS, those with MS walked a lower distance at 6MWT (438±110 vs 408±123 m; p <0.05), had a lower maximal exercise capacity (7.6±1.8 vs 9.3±1.2 MET; p <0.05) and a lower heart rate recovery (HRR) (16±9 vs 22±8; p <0.05). Male patients with or without MS had a similar degree of functional recovery (51%) while women with MS had a significantly lower recovery than nMS (20% vs 40%). In a multivariate logistic regression model, including body mass index, age, gender hypertension, ejection fraction and diabetes, MS predicted a reduced performance at 6MWT in the overall population (OR 1.4, 95% CI 1.7 to 2.4) and in women (OR 1.31; 95% CI 1.20–1.62), while it was not predictive in males. Conclusions: CAD patients with MS have lower functional recovery and HRR than nMS. However MS is an independent predictor of lower exercise capacity only in female gender. [Copyright &y& Elsevier]

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]

The heart rate regulation problem is addressed for the well-known second order nonlinear model of the human heart rate response during treadmill/cycle-ergometer exercises. The mainly restrictive stability & global attractivity constraint in the literature, being constituted by an inequality involving four constant parameters of such a nonlinear model, is definitely removed. Nonlinear analytical arguments and design steps are innovatively presented to achieve heart rate regulation when model parameters satisfy the so-called 'instability constraint', with just stability & local attractivity properties being involved. Experimental results are included to illustrate all the theoretical derivations. [ABSTRACT FROM AUTHOR]