Trimetazidine potentiates the effects of exercise training in patients with ischemic cardiomyopathy referred for cardiac rehabilitation.

BACKGROUND: Patients referred for cardiac rehabilitation may take advantage from combining trimetazidine (TMZ) with exercise training (ET), as both treatments produce similar effects in the cardiovascular system. It is, however, unknown whether the combination of TMZ with ET may determine greater improvements in functional capacity and endothelial function than ET alone. DESIGN: A randomized longitudinal controlled study. METHODS: We studied 116 patients (97 men and 19 women, mean age 58+/-9 years) with ischemic heart disease and left ventricular dysfunction who were referred for cardiac rehabilitation. Coronary risk factors were present in 82 patients (diabetes in 28 patients). Patients were randomized into three matched groups. A group (TMZ+training, TT, n=30) received TMZ at doses of 20 mg three times daily orally for 8 weeks in addition to standard medications and underwent a supervised program of ET at 60% of oxygen uptake at peak, three times a week for 8 weeks. A group (exercise, E, n=30) completed the ET program without receiving TMZ. A control group (C, n=26) was neither exercised nor received TMZ. A fourth group (TMZ, n=30) receiving TMZ 20 mg three times daily for 8 weeks was also studied. On study entry and at 8 weeks all patients underwent echocardiography, cardiopulmonary exercise testing, and vasomotor reactivity of the brachial artery. RESULTS: Oxygen uptake at peak was significantly increased in the TT (25%), TMZ (15.1%), and E group (15.3%) (P<0.001 TT vs. C; P<0.05 vs. TMZ and E). Left ventricular ejection fraction was also improved in TT (18.4%), TMZ (15.7%), and E (12.9%) (P<0.001 TT vs. C; P<0.05 vs. TMZ and E), as a result of reduction in end-systolic volume. The endothelium-dependent dilation was similarly improved (P<0.001 TMZ vs. C; P<0.05 vs. TMZ and E). The most significant improvements were observed in the subgroup TT with multiple risk factors. CONCLUSION: The addition of TMZ to ET determined greater improvements in functional capacity, left ventricular ejection fraction, and endothelium-dependent dilation than TMZ or ET given alone. No differences between improvements after TMZ and E as compared with controls were observed.

Waltz dancing in patients with chronic heart failure: new form of exercise training.

BACKGROUND: There is evidence that aerobic exercise improves functional capacity in patients with New York Heart Association (NYHA) class II and III chronic heart failure. However, it is unknown whether dancing is safe and able to improve functional capacity in patients with chronic heart failure. METHODS AND RESULTS: We prospectively studied 130 patients with stable chronic heart failure (107 men; mean age, 59+/-11 years) in New York Heart Association class II and III and left ventricle ejection fraction <40%. Patients were randomized to supervised aerobic exercise training at 70% of peak o(2) 3 times a week for 8 weeks (group E, n=44) or to a dance protocol of alternate slow (5 minutes) and fast (3 minutes) waltz lasting 21 minutes (group D, n=44). A group that did not undergo exercise training served as control (group C, n=42). On study entry and at 8 weeks, all patients underwent cardiopulmonary exercise testing on a cycle ergometer until volitional fatigue, 2D-echo with Doppler, and endothelium-dependent dilation of the brachial artery. Heart rate was 111+/-15 bpm during exercise training and 113+/-19 bpm during dancing (P=0.59). Peak o(2), anaerobic threshold, e/co(2) slope, and o(2)/W slope were all similarly improved in both E and D groups (+16% and 18%, 20% and 21%, 14% and 15%, 18% and 19%, respectively; P not significant for all comparisons; P<0.001 versus controls). Endothelium-dependent relaxation was also similarly improved (group E, from 2.6+/-1.3% to 5.2+/-1.5%, P<0.001 versus control; group D, from 2.2+/-1.4% to 5.0+/-1.5%, P<0.001 versus control for both E and D). The change in peak o(2) in E and D groups was correlated with changes in peak velocity of early filling wave/peak velocity of late filling ratio (r=-0.58, P<0.001) and endothelium-dependent dilation (r=0.64, P<0.001). Untoward events were rare in both E and D groups. CONCLUSIONS: In patients with stable chronic heart failure, waltz dancing is safe and able to improve functional capacity and endothelium-dependent dilation similar to traditional aerobic exercise training. Waltz dancing may be considered in clinical practice in combination with aerobic exercise training or as an alternative to it.

Clinical benefits of a metabolic approach in the cardiac rehabilitation of patients with coronary artery disease.

Patients referred for cardiac rehabilitation may benefit from combining trimetazidine with exercise training because both treatments produce synergic benefits on the cardiovascular system. There is evidence that trimetazidine improves left ventricular (LV) function in patients with ischemic and diabetic cardiomyopathy by shifting the cellular energy substrate reference from fatty acids to glucose oxidation, and that this effect is associated with a better outcome. Recently, results have demonstrated that trimetazidine improves radial artery endothelium-dependent relaxation related to its antioxidant properties. Similarly, exercise training has been demonstrated to improve diastolic filling and systolic function in patients with ischemic cardiomyopathy, in relation to enhanced perfusion and contractility of dysfunctional myocardium. Patients with viable myocardium, in theory, should have the greatest benefits because trimetazidine improves contractility of dysfunctional hibernating/stunned myocardium, whereas exercise has documented efficacy in improving endothelial vasomotor response of coronary arteries, stimulating coronary collateral circulation and small vessel growth, improving LV function, and increasing functional capacity. At present, there are no published reports about the efficacy of the combination of trimetazidine with exercise training. In this article, we discuss the rationale for using trimetazidine in cardiac rehabilitation, the identification of patients referred for cardiac rehabilitation who might benefit the most from the addition of trimetazidine to standard therapy, and the documented benefits.

Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have sexual dysfunction that impairs quality of life. Recent trials have demonstrated that exercise training (ET) improves quality of life (QOL) of CHF patients, but it is not established whether this benefit may be associated with an improvement in sexual dysfunction. OBJECTIVE: To determine whether ET can improve sexual dysfunction in patients with CHF. METHODS: We prospectively studied 59 male patients (57+/-9 years) with stable CHF in sinus rhythm and without prostatic disease. Patients were randomized into two groups. A group (T, n = 30) underwent supervised cycle ergometer ET at 60% of peak VO2, three times a week, 60 min each session, for 8 weeks. A group (NT, n = 29) was not exercised. Medications were not changed during the study. On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing, brachial artery endothelium-dependent (ED) and endothelium-independent (EI) vasomotor responses, QOL and sexual activity profile assessment (SAP) by questionnaire. RESULTS: At 8 weeks, no changes were observed in control patients. In trained patients, however, peak VO2 improved by 18% (P < 0.005) and was correlated with QOL (r = 0.80; P < 0.001). Flow-mediated dilation improved in trained patients (from 2.29+/-1.13% to 5.04+/-1.7%, P = 0.0001), while EI dilation (after 0.3 mg sublingual NTG) did not. In group T, all three domains (i.e. Domain 1=relationship with the partner; Domain 2 = quality of penile erection; Domain 3 = personal wellness) were significantly improved from baseline (total score patients: from 3.49+/-3.4 to 6.17+/-3.2, P < 0.001; partners: from 2.47+/-2.7 to 4.87+/-2.5, P < 0.001). Pre-post training change in SAP total score was correlated with changes in coronary risk profile (r = -0.49; P = 0.01), peak VO2 (r = 0.67; P < 0.001) and QOL (r = 0.73; P = 0.01). Multivariate analysis selected the improvement in ED-vasomotor response as the strongest independent predictor of SAP improvement (r = 0.63, P < 0.001). CONCLUSIONS: In stable CHF, cycle ergometer ET significantly improves brachial artery endothelial dysfunction, suggesting a systemic effect of leg exercise. This benefit was correlated with improvements in sexual activity.