Cardiopulmonary exercise testing is more accurate than ECG-stress testing in diagnosing myocardial ischemia in subjects with chest pain.

BACKGROUND: Cardiopulmonary exercise stress testing (CPET) is used to grade the severity of heart failure and to assess its prognosis. However it is unknown whether CPET may improve diagnostic accuracy of standard ECG stress testing to identify or exclude obstructive coronary artery disease (O-CAD) in patients with chest pain. METHODS: We prospectively studied 1265 consecutive subjects (55 ± 8 years, 156 women) who were evaluated with ECG stress testing (ET) for chest pain. No one had a documented O-CAD. All patients performed an incremental CPET with ECG recordings on an electronically braked cycle ergometer. RESULTS: Of 1265 patients, 73 had a positive CPET and 1192 had a negative CPET. Seventy-three patients with a positive CPET and 71 patients with a negative CPET agreed to undergo nuclear SPECT imaging and coronary angiography. Follow-up lasted 48 ± 7 months. As compared with ET, sensitivity, specificity, PPV and NPV were all improved significantly (ET: 48%, 55%, 33%, 95%; CPET: 88%, 98%, 73%, 99%, respectively, P<0.001). Patients with both peak VO2>91% of predicted VO2 max and absence of VO2-related signs of myocardial ischemia had no evidence of O-CAD in 100% of cases. Cardiac events occurred in 32 patients with a positive CPET and 8 patients with a negative CPET (log rank 18.2, P<0.0001). CONCLUSIONS: In patients with chest pain, CPET showed a better diagnostic and predictive accuracy than traditional ET to detect/exclude myocardial ischemia. Its use should be encouraged among physicians as a first line diagnostic tool in clinical practice.

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.

Effects of trimetazidine on myocardial perfusion and left ventricular systolic function in type 2 diabetic patients with ischemic cardiomyopathy.

AIMS: To determine whether short-term treatment with trimetazidine (TMZ), an antiischemic agent that directly inhibits fatty acid oxidation and results in stimulation of glucose oxidation, may improve myocardial perfusion and left ventricular systolic function in diabetic patients with ischemic cardiomyopathy. METHODS AND RESULTS: We studied 34 clinically stable patients with type 2 diabetes mellitus (DM) and documented multivessel coronary artery disease (29 men and 5 women, mean age 54 +/- 9 years) with depressed systolic function (left ventricular ejection fraction 38 +/- 6%). Patients were randomized into two groups. One group received TMZ (20 mg tid) for 3 months (n = 19), while another group received a placebo during the same period (n = 15). On study entry and at 3 months, all patients underwent a gated Single Photon Emission Computed Tomography (SPECT) myocardial scintigraphy with a 2-day stress(Bruce)-rest protocol (500 MBq tetrofosmin). At 3 months, TMZ-treated patients had a significant improvement in systolic wall thickening (P < 0.05) and ejection fraction (P = 0.007) as compared with control patients. These effects were more marked in patients with more severe reversible perfusion defects on initial evaluation and were not associated with changes in myocardial defects (P = 0.38). Total exercise time was also improved in TMZ-treated patients (20.5%, P < 0.05 vs. controls). CONCLUSIONS: In diabetic cardiomyopathy, short-term TMZ improved left ventricular systolic function and functional capacity despite no change in myocardial perfusion. These benefits were more evident in patients with more severe perfusion defects on initial evaluation, suggesting that chronic myocardial ischemia is a requirement for the effects of TMZ on left ventricular systolic performance.

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.

Coenzyme Q10 and exercise training in chronic heart failure.

AIMS: There is evidence that plasma coenzyme Q(10) (CoQ(10)) levels decrease in patients with advanced chronic heart failure (CHF). However, it is not known whether oral CoQ(10) supplementation may improve cardiocirculatory efficiency and endothelial function in patients with CHF. METHODS AND RESULTS: We studied 23 patients in NYHA class II and III (20 men, three women, mean age 59+/-9 years) with stable CHF secondary to ischaemic heart disease [ejection fraction 37+/-7%], using a double-blind, placebo-controlled cross-over design. Patients were assigned to each of the following treatments: oral CoQ(10) (100 mg tid), CoQ(10) plus supervised exercise training (ET) (60% of peak VO(2), five times a week), placebo, and placebo plus ET. Each phase lasted 4 weeks. Both peak VO(2) and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ(10) and after ET as compared with placebo. CoQ(10) main effect was: peak VO(2)+9%, EDDBA +38%, systolic wall thickening score index (SWTI) -12%; ET produced comparable effects. CoQ(10) supplementation resulted in a four-fold increase in plasma CoQ(10) level, whereas the combination with ET further increased it. No side effects were reported with CoQ(10). CONCLUSIONS: Oral CoQ(10) improves functional capacity, endothelial function, and LV contractility in CHF without any side effects. The combination of CoQ(10) and ET resulted in higher plasma CoQ(10) levels and more pronounced effects on all the abovementioned parameters. However, significant synergistic effect of CoQ(10) with ET was observed only for peak SWTI suggesting that ET amplifies the already described effect of CoQ(10) on contractility of dysfunctional myocardium.

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.

Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure.

BACKGROUND: There is evidence that plasma CoQ(10) levels decrease in patients with advanced chronic heart failure (CHF). OBJECTIVE: To investigate whether oral CoQ(10) supplementation could improve cardiocirculatory efficiency in patients with CHF. METHODS: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 +/- 9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 +/- 7%), using a double-blind, placebo-controlled cross-over design. Patients were assigned to oral CoQ(10) (100 mg tid) and to placebo for 4 weeks, respectively. RESULTS: CoQ(10) supplementation resulted in a threefold increase in plasma CoQ(10) level (P < 0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ(10) supplementation (+12.1 and 15.6%, respectively, P < 0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P < 0.0001) in relation to a decrease in LV end-systolic volume index (from 57 +/- 7 mL/m(2) to 45 mL/m(2), P < 0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ(10) levels (r = -0.52, P < 0.005). Peak VO(2) was also improved after CoQ(10) as compared with placebo (+13%, <0.005). No side effects were reported with CoQ(10). CONCLUSIONS: Oral CoQ(10) improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity.

Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing.

BACKGROUND: The objective of the study was to identify the parameter(s) of cardiopulmonary exercise testing (CPET) that can detect exercise-induced myocardial ischaemia (EIMI), and to determine its diagnostic accuracy for identifying patients with coronary artery disease (CAD). METHODS AND RESULTS: We prospectively studied 202 consecutive patients (173 men, 29 women, mean age 55.7+/-10.8 years) with documented CAD. All patients underwent an incremental exercise stress testing (ECG-St) with breath-by-breath gas exchange analysis, followed by a 2-day stress/rest gated SPECT myocardial scintigraphy (GSMS) as the gold standard for ischaemia detection. ROC analysis selected a two-variable model-O(2)pulse flattening duration, calculated from the onset of myocardial ischaemia to peak exercise, and deltaVO(2)/deltawork rate slope-to predict EIMI by CPET. GSMS identified 140 patients with reversible myocardial defects, with a Summed Difference Score (SDS) of 9.7+/-2.8, and excluded EIMI in 62 (SDS 1.3+/-1.6). ECG-St had low sensitivity (46%) and specificity (66%) to diagnose EIMI as compared with CPET (87% and 74%, respectively). CONCLUSIONS: The addition of gas exchange analysis improves the diagnostic accuracy of standard ECG stress testing in identifying EIMI. A two-variable model based on O(2)pulse flattening duration and deltaVO(2)/deltawork rate slope had the highest predictive ability to identify EIMI.