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PubMed2005

Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy.

STUDY OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension. DESIGN: Prospective, nonrandomized, open-label study. SETTING: University hospital. PATIENTS: Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3). INTERVENTIONS: Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy. MEASUREMENTS AND RESULTS: Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (+/- SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66 m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and - 0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication. CONCLUSION: Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials.

Adult↗
PubMed1997

Effects of pimobendan on exercise tolerance and quality of life in patients with heart failure.

There has been an intensive search for safe and clinically effective inotropic agents for use as adjunctive therapy in patients with advanced heart failure. Pimobendan is a benzimidazole-pyridazinone derivative with calcium-sensitizing properties that increases myocardial contractile force without increasing intracellular calcium. This review summarizes the data from five controlled, randomized prospective trials of pimobendan that demonstrate significant improvements in exercise capacity and quality of life in patients with heart failure. The clinical benefits of pimobendan found in these trials contrast with the adverse experience noted previously with milrinone and enoximone. This may be related to the different mechanism of action of pimobendan or to a study design that permitted examination of a lower dosage. These cumulative data suggest that pimobendan may have a useful adjunctive role in heart failure and that further assessment of its effects on overall mortality is needed.

Cardiotonic Agents↗
PubMed2002

Muscle metabolism and exercise tolerance in COPD.

This article explores the hypothesis that dyspnea in patients with COPD arises from an imbalance between the load placed on the respiratory muscle pump and its capacity. Evidence to support this concept is presented, and possible therapeutic approaches are discussed.

Exercise Therapy↗
PubMed1986

A computer program for the interpretation of exercise tolerance tests.

A software package has been developed to interpret exercise test data recorded by a metabolic measurement cart (MMC). This package reduces and interprets the exercise test data relative to population and patient specific criteria. The data flow for the data reduction and report printing is described. The data structures used in this processing are illustrated. The application of structured programming, a real-time executive and an easy-to-read language--such as Pascal--is illustrated for the implementation of a medical instrument. Issues of prediction and interpretation relative to exercise testing are discussed.

Diagnosis, Computer-Assisted↗
PubMed2005

Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review.

Greater omega-3 fatty acid consumption is associated with reduced cardiovascular disease risk. Though the mechanisms of their effect are unclear, they may involve lesion formation and heart function. We conducted a systematic review of the clinical literature on the effect of omega-3 fatty acids on measures of vascular structure and function. We included studies that assessed fish and plant sources of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid IMT, and exercise capacity. Compared to placebo, the summary risk ratio of coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12 randomized controlled trials. Two prospective studies reported increased carotid IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish, fish oil or ALA consumption. Three randomized trials and three uncontrolled studies reported small non-significant improvements in exercise capacity with fish oil. Overall, little or no effect of fish oil was found for a variety of markers of cardiovascular disease risk. There are insufficient studies to draw conclusions about the effect of ALA. The dearth of long term data on fish consumption or omega-3 fatty acid supplementation on measures of cardiovascular disease risk severely limits our ability to draw definitive conclusions at this time.

Carotid Arteries↗
PubMed1993

Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease.

This study prospectively assessed the time course, magnitude and mechanism of the hemodynamic changes after restoration of sinus rhythm in patients with chronic atrial fibrillation (AF) unassociated with valvular disease. Severe cardiac dysfunction may occur after chronic supraventricular tachycardia in patients with and without underlying cardiac disease. Improvement may follow abolishment of the arrhythmia or adequate slowing of the ventricular rate. Eight patients were studied with a mean previous duration of AF of 10 +/- 9 months. Ejection fraction, exercise capacity and the atrial contribution to the left ventricular filling (only during sinus rhythm) were studied before cardioversion, after cardioversion and 1 week, 1 month and 6 months thereafter. A significant improvement in ejection fraction from 36 +/- 13 to 53 +/- 8% (p < 0.05) occurred at 1 month after cardioversion. Concomitantly, peak oxygen consumption had increased at 1 month, from 20.1 +/- 7 to 25.2 +/- 6 ml/min/kg (p < 0.05). Thereafter, no further improvement in hemodynamic parameters occurred. The atrial systole improved already at 1 week (from 3 +/- 5 to 16 +/- 11%, p < 0.05) and remained unchanged thereafter. Thus, restoration of sinus rhythm was associated with a delayed improvement in ejection fraction and maximal exercise capacity, preceded by an early restoration of atrial contractility and an acute slowing of the heart rate. The discrepancy in time course of restoration of atrial and ventricular function parameters suggests that an intrinsic left ventricular cardiomyopathy is present in patients with AF.

Aged↗
PubMed2003

Improved exercise tolerance and quality of life with cardiac rehabilitation of older patients after myocardial infarction: results of a randomized, controlled trial.

BACKGROUND: Whether cardiac rehabilitation (CR) is effective in patients older than 75 years, who have been excluded from most trials, remains unclear. We enrolled patients 46 to 86 years old in a randomized trial and assessed the effects of 2 months of post-myocardial infarction (MI) CR on total work capacity (TWC, in kilograms per meter) and health-related quality of life (HRQL). METHODS AND RESULTS: Of 773 screened patients, 270 without cardiac failure, dementia, disability, or contraindications to exercise were randomized to outpatient, hospital-based CR (Hosp-CR), home-based CR (Home-CR), or no CR within 3 predefined age groups (middle-aged, 45 to 65 years; old, 66 to 75 years; and very old, >75 years) of 90 patients each. TWC and HRQL were determined with cycle ergometry and Sickness Impact Profile at baseline, after CR, and 6 and 12 months later. Within each age group, TWC improved with Hosp-CR and Home-CR and was unchanged with no CR. The improvement was similar in middle-aged and old persons but smaller, although still significant, in very old patients. TWC reverted toward baseline by 12 months with Hosp-CR but not with Home-CR. HRQL improved in middle-aged and old CR and control patients but only with CR in very old patients. Complications were similar across treatment and age groups. Costs were lower for Home-CR than for Hosp-CR. CONCLUSIONS: Post-MI Hosp-CR and Home-CR are similarly effective in the short term and improve TWC and HRQL in each age group. However, with lower costs and more prolonged positive effects, Home-CR may be the treatment of choice in low-risk older patients.

Aged↗
PubMed1996

Prospective studies on left ventricular geometric patterns and exercise tolerance in unmedicated men with borderline and mild hypertension.

OBJECTIVE: This study was designed and conducted to assess the clinical significance of left ventricular geometric patterns and physical fitness in subjects with untreated borderline and mild hypertension. METHODS: Symptom-limited maximal treadmill stress testings and echocardiographic examinations were administered to 192 previously unmedicated men. Left ventricular geometric patterns were determined by the combined criteria of left ventricular mass index and relative wall thickness. Subjects whose left ventricular mass index was < 125 g/m2 were followed up for more than 3 years. RESULTS: Normalized treadmill time was lower and pressure rate products at peak exercise were higher in patients with concentric hypertrophy than in those with normal geometry. Of the 77 patients who revealed left ventricular mass index at baseline < 125 g/m2 and who were successfully followed without medication for more than 3 years, 18 demonstrated concentric hypertrophy at the final follow-up examination. During the follow-up period, these 18 patients had significant further augmentation of concentric geometric features, significant decreases in both cardiac output and normalized treadmill time, and significant increases in casual blood pressure and total peripheral resistance compared with those at baseline. CONCLUSION: Patients with concentric hypertrophy exhibited slightly but significantly impaired levels of physical fitness and cardiac work efficiency, and the progression of concentric hypertrophy demonstrated further impairments of these conditions. Therefore, not only lowering blood pressure, but also improving left ventricular hypertrophy, cardiovascular hemodynamics, and physical fitness might be required in patients with concentric hypertrophy.

Adult↗
PubMed2006

Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease.

BACKGROUND: To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication. METHOD: Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training. RESULTS: Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group. CONCLUSION: These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.

Aged↗
PubMed2002

Cardiovascular hemodynamics and exercise tolerance in thyroid disease.

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiovascular performance are detected with small variations in thyroid hormone serum concentrations. Most patients with thyroid disease experience cardiovascular manifestations, and the most serious complications of thyroid dysfunction occur as a result of cardiac involvement. The increased metabolic state and oxygen consumption that occur in hyperthyroid patients require an increased supply of oxygen and removal of metabolic products from the periphery. This is accomplished by increasing the cardiac output to meet the needs of the periphery. Circulation time is decreased in hyperthyroid patients, and a lowered arterial resistance and increased venous resistance promote the return of blood to the heart. Thyroid hormones may significantly decrease the strength of respiratory and skeletal muscles and affect regulatory mechanisms of adaptation to incremental effort. In hyperthyroidism, cardiovascular exercise testing and analysis of respiratory gas exchange demonstrate low efficiency of cardiopulmonary function as well as impaired chronotropic, contractile, and vasodilatatory reserves, which are reversible when euthyroidism is restored. During exercise, the increment (delta) of minute ventilation (respiratory rate x tidal volume), and oxygen pulse (oxygen uptake per heart beat) are significantly lower in dysthyroidism versus euthyroidism. Especially in older patients with thyroid dysfunction, markedly reduced workload, delta ejection fraction, and delta heart rate, both at the anaerobic threshold as well as at maximal exercise, are observed. In thyrotoxicosis, mitochondria oxidative dysfunction during exercise mostly causes intracellular acidosis, whereas in hypothyroidism, inadequate cardiovascular support appears to be one of the principal factors involved. These abnormalities partly explain why subjects with dysthyroidism are intolerant to exertion. Thus, in thyroid disease, both cardiac structures and function may remain normal at rest, however impaired cardiovascular and respiratory adaptation to effort becomes unmasked during exercise.

Age Factors↗
PubMed2002

Effect of non-insulin-dependent diabetes mellitus on pulmonary function and exercise tolerance in chronic congestive heart failure.

In chronic congestive heart failure (CHF), backward effects of left ventricular dysfunction alter pulmonary volumes and gas diffusion. Some of these disorders are detected in some patients with diabetes mellitus, possibly due to a microangiopathic process and nonenzymatic glycosylation of lung tissue proteins. We explored the possibility that coexistence of non-insulin-dependent diabetes mellitus (NIDDM) may potentiate the deterioration of lung function in CHF. In 20 normoglycemic patients (group 1) and in 20 patients with NIDDM (group 2), with New York Heart Association class II to III CHF due to idiopathic or ischemic cardiac disease, and in 20 controls (groups were age- and gender-matched), we investigated cardiac function, pulmonary volumes, carbon monoxide diffusion (DL(CO)) and its alveolar-capillary membrane (D(M)) subcomponent, oxygen uptake and dead space-to-tidal volume ratio (pVD/VT) at peak exercise (individualized ramp test), and slope of ventilation-to-carbon dioxide production ratio (VE/VCO(2)) during exercise. Although, compared with reference subjects, both patient groups had similar variations in left ventricular diastolic volume, ejection fraction, and pulmonary wedge pressure; in group 2 lung volumes, DL(CO), D(M), and oxygen uptake were significantly more reduced; in this group there was no overlap of individual results of DL(CO) and D(M) with those in controls; VE/VCO(2) slope and pVD/VT also were significantly increased, and inversely correlated with D(M). Thus, coexistence of NIDDM makes pulmonary dysfunction worse in CHF, and significantly enhances exercise intolerance.

Analysis of Variance↗
PubMed2005

Exercise tolerance and daily life in McArdle's disease.

McArdle's disease is a common disorder of muscle metabolism and is due to myophosphorylase deficiency. The major complaint of patients with this disease is effort intolerance. Although the clinical features of affected patients are well known, their daily lifestyle is not well documented. The main objective of this work was to assess their mean daily energy expenditure (DEE) and compare it with control subjects. Thirty patients and 87 control subjects completed a questionnaire. A 3-day self-record of daily physical activities was used to estimate the mean DEE for patients and control subjects. A separate section of the questionnaire was used to assess patients' clinical features and daily lifestyle. The DEE of patients (44.1 +/- 6.9 kcal/kg) was not significantly different from control subjects (44.5 +/- 5.6 kcal/kg). Half of the patients with McArdle's disease performed a daily physical leisure activity as sport, sometimes at a high level (17%). Despite large individual variation, physical abilities and patients' symptoms were negatively correlated. Physical leisure activity significantly decreased the sensation of muscle pain (P < 0.03). These findings show that patients with McArdle's disease do not have a strictly sedentary lifestyle. Moreover, physical exercise appears to have positive effects on the main clinical features, such as effort intolerance. Thus, regular, moderate physical activity may be beneficial in McArdle's disease.

Activities of Daily Living↗
PubMed1995

Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.

This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [+/-SD] 26.5% [+/-6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure: death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic. At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P = 0.101 by ANCOVA and 0.010 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P = 0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20%, of patients, P = 0.002), as were hospitalizations (3% vs 12% of patients, P = 0.002) and study discontinuations (2% vs 12% of patients, P < 0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P = 0.723). In addition, symptoms of dyspnoea (P = 0.017), fatigue (P = 0.019), and NYHA functional class (P = 0.008) improved with fosinopril relative to placebo. In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure.

Angiotensin-Converting Enzyme Inhibitors↗