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Background: This small clinical trial tested the hypothesis that the addition of inspiratory muscle training (IMT) to aerobic exercise training (AE) results in further improvement in cardiorespiratory responses to exercise than those obtained with AE in patients with chronic heart failure (CHF) and inspiratory muscle weakness (IMW)., Methods: Twenty-four patients with CHF and IMW (maximal inspiratory pressure <70% of predicted) were randomly assigned to a 12-week program of AE plus IMT (AE + IMT, n = 12) or to AE alone (AE, n = 12). Before and after intervention, the following measures were obtained: maximal inspiratory muscle pressure (PI(max)), peak oxygen uptake (Vo(2)peak), peak circulatory power, oxygen uptake efficiency slope, ventilatory efficiency, ventilatory oscillation, oxygen uptake kinetics during recovery (T(1/2)Vo(2)), 6-minute walk test distance, and quality of life scores., Results: Compared to AE, AE + IMT resulted in additional significant improvement in PI(max) (110% vs 72%), Vo(2)peak (40% vs 21%), circulatory power, oxygen uptake efficiency slope, ventilatory efficiency, ventilatory oscillation, and T(1/2)Vo(2). Six-minute walk distance and quality of life scores improved similarly in the 2 groups., Conclusion: This randomized trial demonstrates that the addition of IMT to AE results in improvement in cardiorespiratory responses to exercise in selected patients with CHF and IMW. The clinical significance of these findings should be addressed by larger randomized trials.

Background: In nondiabetic patients with stable angina, combined treatment with hemodynamic agents and trimetazidine is well-tolerated and effective in controlling ischemia. This study aims to evaluate the antiischemic and metabolic effects of trimetazidine in patients with type 2 diabetes mellitus, not eligible for revascularization, who remained symptomatic despite the use of at least 2 antianginal agents., Methods: A randomized, double-blind, crossover clinical trial was used. Ten patients were randomized to receive trimetazidine (20 mg, 3 times a day) or placebo for 6-week periods. At baseline and at the end of each 6-week intervention period, clinical and biochemical evaluations, exercise testing, 24-hour ambulatory blood pressure, and Holter monitoring were performed., Results: During trimetazidine therapy, patients had significant improvement on angina functional class (P < .05), with decrease in the number of weekly angina episodes (1.5 +/- 0.8 vs 0.4 +/- 0.7, P < .01), and in sublingual nitrate doses (1.4 +/- 0.7 mg vs 0.1 +/- 0.3 mg, P < .001). Time to 1-mm ST-segment depression during exercise test was increased after trimetazidine use (229 +/- 126 seconds at baseline, 276 +/- 101 seconds after placebo, and 348 +/- 145 seconds after trimetazidine, P < .001). No differences were observed between treatment periods on mean 24-hour blood pressure, heart rate, and rate-pressure product evaluated concomitantly with ambulatory blood pressure and Holter monitoring. Glycemic and lipid profiles were similar after trimetazidine and placebo use., Conclusions: In patients with diabetes who remain symptomatic, the addition of trimetazidine improves symptoms and exercise responses without hemodynamic or metabolic changes. The present data suggest that trimetazidine may be an effective adjunct therapy for these patients, but further investigation is needed to confirm these findings.

Background: Increased ventricular arrhythmia density and reduced heart rate variability are associated with risk of death in patients with heart failure. Cholinesterase inhibition with pyridostigmine bromide increases heart rate variability in normal subjects, but its effect on patients with heart failure is unknown. In this study, we tested the hypothesis that short-term administration of pyridostigmine bromide, a cholinesterase inhibitor, reduces ventricular arrhythmia density and increases heart rate variability in patients with congestive heart failure., Methods: Patients with heart failure and in sinus rhythm participated in a double-blind, cross-over protocol, randomized for placebo and pyridostigmine (30 mg orally 3 times daily for 2 days). Twenty-four hour electrocardiographic recordings were performed for arrhythmia analysis and for the measurement of time domain indices of heart rate variability. Patients were separated into 2 groups, according to their ventricular arrhythmia density. The arrhythmia group (n = 11) included patients with >10 ventricular premature beats (VPBs) per hour (VPBs/h), and the heart rate variability group (n = 12) included patients with a number of VPBs in 24 hours not exceeding 1% of the total number of R-R intervals., Results: For the arrhythmia group, pyridostigmine resulted in a 65% reduction of ventricular ectopic activity (placebo 266 +/- 56 VPBs/h vs pyridostigmine 173 +/- 49 VPBs/h, P =.03). For the heart rate variability group, pyridostigmine administration increased mean R-R interval (placebo 733 +/- 22 ms vs pyridostigmine 790 +/- 33 ms, P =.01), and in the time domain indices of heart rate variability root-mean-square of successive differences (placebo 21 +/- 2 ms vs pyridostigmine 27 +/- 3 ms, P =.01) and percentage of pairs of adjacent R-R intervals differing by >50 ms (placebo 3% +/- 1% vs pyridostigmine 6% +/- 2%, P =.03)., Conclusion: In patients with heart failure, pyridostigmine reduced ventricular arrhythmia density and increased heart rate variability, most likely due to its cholinomimetic effect. Long-term trials with pyridostigmine in heart failure should be conducted.

Background: Parasympathetic dysautonomia is an established feature of advanced Chagas cardiomyopathy. However, in the absence of cardiac involvement, the presence of vagal dysfunction remains controversial. In a cross-sectional study, we compared patients with Chagas disease without cardiac involvement and healthy individuals by three different methods to determine whether vagal dysfunction is present in the early phase of Chagas disease., Methods: Sixty-one patients with Chagas disease without cardiac involvement and 38 controls were submitted to respiratory sinus arrhythmia test and 24-hour Holter monitoring. Vagal heart influences were assessed by the expiratory/inspiratory (E/I) ratio, time-domain indexes of heart rate variability (HRV), and by the quantification of a 3-dimensional return map., Results: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. Compared with the control group, patients with Chagas disease had significantly lower values of the E/I ratio (mean +/- SD: 1.38 +/- 0.02 and 1.25 +/- 0.02, P <.004) and short-term indexes of HRV (median [interquartile range]-rMSSD: 23 [18-27] and 17 [13-23], P =.00; pNN50: 11 [7-17] and 6 [2-12], P =.00). P(3), a beat-to-beat HRV index derived from the 3-dimensional return map, also was significantly reduced in the Chagas disease group (mean +/- SD: 118 +/- 5 vs 100 +/- 4, P =.00). None of these indexes of vagal heart control were significantly correlated with left ventricular function or to the presence of esophageal radiologic abnormalities., Conclusion: Parasympathetic dysautonomia is an independent and early phenomenon in Chagas disease and may precede left ventricular systolic dysfunction.

Background: Some antiarrythmic agents that may increase mortality rates have been shown to reduce heart rate variability in patients with heart failure. Amiodarone is a potent antiarrhythmic agent that may reduce mortality rates in heart failure, but little is known about its effects on heart rate variability., Methods and Results: The purpose of this study was to evaluate the effect of partial arrhythmia suppression by amiodarone on indexes of heart rate variability in patients with heart failure. Ten clinically stable patients in New York Heart Association class II-III received amiodarone during a 4-week period (600 mg every day for 14 days and 300 mg every day for 16 days), and 24-hour Holter recordings were performed before and after treatment. Heart rate variability indexes were calculated by a semiautomatic method that applies a 20% filter to the temporal series, excluding ectopy and compensatory pauses. After amiodarone administration, there was a significant reduction in pNN50 from 8% +/- 7% to 3% +/- 2% (p < 0.05) and there was a trend toward reduction in rMSSD (p = 0.06). Other time domain indexes did not change significantly. Spectral analysis demonstrated a significant reduction of low-frequency components (421 +/- 122 to 151 +/- 25 msec2; p < 0.05) and total power (1503 +/- 314 to 609 +/- 144 msec2, p < 0.05). Multivariate analysis showed that the observed reduction in pNN50 was strongly associated with the number and the reduction of ventricular premature contractions before and after amiodarone administration (r2 = 0.94; p < 0.01)., Conclusions: These findings indicate that despite the use of software corrections for arrhythmia, short-term time domain indexes of heart rate variability may be affected by partial suppression of ectopy.

To evaluate the effects of a high complex carbohydrate, low lipid diet on the management of coronary artery disease, we reviewed data on 32 patients, who had participated in a diet and exercise program, and compared the results with 40 patients who had been managed only with exercise. After a follow-up period of 10 to 16 weeks the patients on the diet-exercise program showed significant reduction in body weight (-6 +/- 2 kg mean +/- standard deviation), serum cholesterol (-43 +/- 41 mg/dl), and triglycerides (-51 +/- 70 mg/dl), while patients who were managed only with exercise had no significant changes in weight or serum lipids. Both the diet-exercise and the exercise groups showed significant improvement in working capacity and reduction in resting systolic blood pressure. Patients on the diet-exercise program had significantly less angina (21.9%) occurring on the exercise test after the program compared to before, even though the same double product was reached. Multiple logistic regression analysis of the data for patients with angina on the exercise test demonstrated that the only significant (p = 0.004) contributor for reduction in angina was the dietary intervention. Beta-blocking drugs did not affect the results. Although randomized controlled trials must be run in order to ascertain the significance of this finding, this study strongly suggests that a low lipid, high carbohydrate diet is a useful addition to exercise in the management of patients with coronary disease.