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Allograft diastolic dysfunction and chronotropic incompetence limit cardiac output response to exercise two to six years after heart transplantation.

BACKGROUND: Because prolonged survival of heart transplant recipients is expected with the current immunosuppressive treatment, the functional capacity of these long-term survivors is of interest. Previous exercise studies showed no objective improvement in exercise tolerance several years after transplantation, but the extent to which chronotropic incompetence and allograft diastolic dysfunction observed early after transplantation may improve over time has not been defined. METHODS: Thirteen untrained heart transplant recipients without symptoms, between 27 and 70 months after transplantation, and 13 age-matched sedentary normal controls underwent maximal upright bicycle exercise testing with simultaneous hemodynamic, radionuclide, and expired gas measurements. RESULTS: Systolic function as measured by ejection fraction was supranormal at rest in the transplant group and normalized with exercise. Despite their maximal exercise effort, transplant recipients had a 60% reduction in their exercise capacity compared with nontransplant recipients. Peak oxygen consumption was similarly reduced by 52%. Cardiac output response to exercise was 43% lower in the transplant group because of a 78% reduction in heart rate reserve and an 18% reduction in maximal stroke volume. Ventricular volumes were similarly reduced after transplantation, but filling pressures remained normal, indicating allograft diastolic dysfunction. Despite the significantly reduced maximal cardiac output, maximal arteriovenous oxygen difference was 25% lower in the transplant recipients, suggesting a peripheral deficit in oxygen handling. CONCLUSIONS: Therefore, patients, 2 to 6 years after transplantation, continue to have a significant reduction in exercise tolerance as a result of a combination of severe chronotropic incompetence, limited stroke volume reserve caused by a reduced ventricular size and allograft diastolic dysfunction, and an abnormality in peripheral oxygen delivery or use. Efforts aimed at improving these factors may further enhance the functional capacity of these long-term survivors of heart transplantation.

Cardiac Output↗

The effects of home-based pulmonary rehabilitation in patients with chronic lung disease.

The purpose of this study was to examine the effects of a home-based pulmonary rehabilitation program on lung function, dyspnea, exercise tolerance, and quality of life in 23 Koreans with moderate to severe chronic lung disease. The outcome measures were forced expiratory volume in 1s (FEV1, % predicted), Borg score, 6 min walking distance (6MWD), and chronic respiratory disease questionnaire (CRDQ). Experimental group (n=15) performed the 8-week home-based pulmonary rehabilitation program, composed of inspiratory muscle training, upper and lower extremity exercise, relaxation, and telephone visit. Patients in control group (n=8) were only given educational advice. The experimental group showed a lower level of exertional dyspnea, more exercise tolerance, and greater improvement in health-related quality of life than the control group (p<0.05). Lung function was not statistically different. This study yielded evidence for the beneficial effects of home-based pulmonary rehabilitation program.

Aged↗

Effects of organized aerobic group training in elderly patients discharged after an acute coronary syndrome. A randomized controlled study.

The aim of this study was to compare the physiological effects of an individually adjusted outpatient group training programme to the standardized recommendations of walking in elderly patients (>65 years) discharged after an acute coronary episode. In all, 101 patients, 20 women and 81 men, aged 65-84 (mean 71) years, were randomized either to a supervised outpatient group training programme during three months (n = 50) or to a control group (n = 51). Exercise tolerance increased from 104 watts to 122 watts (p < 0.001) in the training group and from 102 watts to 105 watts (n.s.) in the control group. Self-estimated level of physical activity was higher in the patients in the training group than in the control group (p < 0.001), as was graded well-being (p < 0.05). Organized aerobic group training can easily be performed in elderly patients after acute coronary syndrome, with results of improved exercise tolerance and a higher self graded well-being.

Acute Disease↗

[Intermediate-term results after Fontan type operation for single ventricle].

From 1983 to 1985, Fontan type operation were successfully performed on five patients with single ventricle. Marked cyanosis disappeared soon after the surgery, and normal exercise tolerance was obtained in all cases but one in the late postoperative period. Compared to marked improvement in the exercise tolerance test, cardiac output remained subnormal both at rest and during exercise even in the late postoperative period. Several types of asymptomatic arrhythmias were observed during the acute postoperative days, but they were not recognized in the intermediate-term postoperative period. Routine blood chemistry studies showed that hepatic function was within normal limits, but hepatic dysfunction was suggested by Indocyanine Green clearance test. Renal function was well preserved after Fontan type procedure. Though cardiac output is subnormal, Fontan type procedure is a safe and effective operation, and intermediate-term state is satisfactory without any signs of heart failure.

Adolescent↗

Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure.

In animals, intermittent sympathomimetic stimulation with dobutamine produces benefits analogous to those of physical conditioning. Longer intermittent or continuous beta-stimulant therapies have not, however, been successful in managing patients with chronic heart failure. We have investigated the role of beta-receptor stimulants in patients with severe chronic heart failure by changing the method of administration to intermittent, very short-duration pulsed intrope therapy (PIT). We studied 10 patients (mean age 64 [SE 2] years) with stable moderate to severe chronic heart failure (ejection fraction 23 [3]%) who received PIT, and 10 control patients matched for age and severity. We infused sufficient dobutamine to raise heart rate to 70-80% maximum for 30 min per day, 4 days per week for 3 weeks. PIT increased exercise tolerance (from 10.4 [1.2] min at baseline to 13.0 [1.5] min at 3 weeks; p < 0.001, 95% CI for difference 1.6 to 3.9) and lowered peripheral vascular resistance (19.8 [3.1] to 17.7 [2.4] mm Hg.min.L-1; p < 0.05, -4.1 to -0.1). PIT produced significant increases in lymphocyte beta-receptor density (502 [110] to 1200 [219] per cell, p < 0.02, 258 to 1138) and chronotropic responsiveness to exercise (change in heart rest to peak exercise 51.0 [3.2] to 57.5 [3.9] beats per min; p < 0.01, 2.9-10.1). Plasma noradrenaline concentrations (2.39 [0.28] to 1.65 [0.19] nmol/L, p < 0.05) were reduced. The patients' symptoms were also improved. By contrast, no change in autonomic function or exercise capacity was seen in the control group. Short-duration PIT induces pharmacological conditioning with improved symptoms, autonomic balance, exercise tolerance, beta-receptor up-regulation, and enhanced chronotropic responsiveness in chronic heart failure.

Aged↗

Comparison of three oxygen delivery systems during exercise in hypoxemic patients with chronic obstructive pulmonary disease.

Oxygen therapy improves submaximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease (COPD). This study compared the standard nasal cannula, reservoir nasal cannula, and a demand flow device in 15 male hypoxemic patients with COPD. On six separate occasions each subject used, in a randomized order, all three systems while completing incremental cycle ergometry and a test circuit composed of tasks that simulate activities of daily living. Oxygen flow required during exercise was 1.8 +/- 0.9 and 2.8 +/- 0.7 L/min for reservoir nasal cannula and standard nasal cannula use, respectively (p < 0.0001). The effect of the three oxygen delivery systems on oxygen saturation (Spo2) during the last 30 s of exercise varied with type of activity. Only during demand flow device use while undressing and dressing was the subjects' Spo2 (90 +/- 3%) significantly lower (p = 0.019). There was a trend toward lower Spo2 with the demand flow device (p = 0.103) during arm work above shoulder level. Although not statistically significant, reservoir nasal cannula use resulted in consistently lower tidal volume and minute ventilation during test circuit activities. Exercise tolerance was not significantly different between the three oxygen delivery systems.

Activities of Daily Living↗

Cardiorespiratory responses to exercise after anatomic repair of atrioventricular discordance with abnormal ventriculoarterial connection.

We evaluated exercise tolerance and cardiorespiratory responses to exercise in patients with atrioventricular discordance (AVD) and abnormal ventriculoarterial connection after anatomic repair. Cardiopulmonary treadmill exercise testing with gas measurement was done 62 times in 19 patients with AVD who had undergone anatomic repair at the National Cardiovascular Center. Exercise duration, oxygen uptake (V(O2)) and heart rate at anaerobic threshold and peak, and oxygen pulse during exercise were significantly lower in patients with AVD after anatomic repair than in controls. Carbon dioxide ventilatory equivalent during exercise was worse in patients with AVD after anatomic repair than in controls. Percentage peak V(O2) significantly correlated positively with percentage peak oxygen pulse and tended to correlate positively with the heart rate increments. Patients with AVD after anatomic repair exhibit impaired responses of heart rate and oxygen pulse with lower exercise capacity. Careful attention should be paid to patients with AVD after anatomic repair in terms of their functional capacity as well as other postoperative complications.

Adolescent↗

Withdrawal phenomenon after abrupt cessation of nifedipine in stable angina pectoris.

We investigated the effect of abrupt cessation of nifedipine after regular administration (20 mg, four times daily) for 5 weeks in seven patients with stable angina pectoris. A rebound decrease in exercise tolerance and increase of exercise-induced myocardial ischaemia were registered on the first day of nifedipine withdrawal.

Angina Pectoris↗

Results of the Bruce treadmill test in children after arterial switch operation for simple transposition of the great arteries.

Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during exercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stress-induced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve.

Age Factors↗

Early and late exercise capacity after acute myocardial infarction treated with recombinant tissue-plasminogen activator.

Thrombolytic therapy salvages jeopardized myocardium and preserves left ventricular function. Therefore, a beneficial effect on exercise tolerance and haemodynamic adaptation to exercise can be anticipated. In the present study the results of bicycle exercise tests, performed at 10 to 14 days and at more than 1 year after infarction, were compared between patients randomized double blindly to recombinant tissue plasminogen activator (rt-PA) or placebo. At 2 weeks, the maximal heart rate (140 vs 130 beats.min-1 P = 0.017), systolic blood pressure (169 vs 161 mmHg, P = 0.018) and pressure-rate product (22907 vs 20865 beats.min-1.mmHg, P = 0.0025) were higher in rt-PA treated patients (n = 145) than in controls (n = 142). At a mean follow-up of 16 months, rt-PA patients (n = 126) performed a higher total and peak work load (733 vs 600 Watts.min, P = 0.027 and 133 vs 100 Watts, P = -0.036, respectively) than control patients (n = 122). During both exercise tests the incidence of clinical or electrocardiographic signs of ischaemia was similar. Multiple regression analysis indicated that age and end-systolic volume were predictors of peak pressure-rate product at 2 weeks (R2 = 0.11, P = 0.0001). Age, sex and left ventricular ejection fraction at discharge were independent predictors of peak work load at 2 weeks (R2 = 0.32, P = 0.0001) and the square root of peak work load at 16 months (R2 = 0.39, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗

Comparative effects of bisoprolol and nitrendipine on exercise capacity in hypertensive patients with regular physical activity.

The aim of this study was to evaluate the long-term effects of administering bisoprolol compared with nitrendipine on the duration of the exercise tolerated by male and female patients, aged 18-65 years, having mild to moderate hypertension and taking regular exercise. In this double-blind, randomized prospective study, 96 patients (85 men and 11 women, 48+/-10 years) formed two groups: 49 in the bisoprolol group, and 47 in the nitrendipine group. After a washout period of 14 days, either 10 mg of bisoprolol or 20 mg of nitrendipine was given daily over a treatment period of 12 weeks. During the treatment period, the stability of the physical training was monitored weekly by using a questionnaire. The results of two maximal triangular exercise tolerance tests (ETTs) on an ergometric bicycle performed at D0 under placebo and at D84 under active treatment were compared. No statistical difference was observed between both groups, concerning age, gender, morphologic characteristics, resting cardiovascular parameters, or physical training. Both groups maintained the same training level throughout the study. No significant differences between the groups were noted for duration of ETT [D0 892+/-284 s, D84, 919+/-267 s (NS) vs. D0 929+/-290 s, D84 904+/-324 s (NS)], or maximal work load [D0 190+/-49 W, D84 197+/-48 W (NS) vs. D0 198+/-49 W, D84 196+/-55 W (NS)]. On the other hand, both groups differed in maximal systolic blood pressure [D0 239+/-24 mm Hg, D84 215+/-22 mm Hg (p<0.001) vs. D0 237+/-24 mm Hg, D84 222+/-27 mm Hg (p<0.05)] (p = 0.05), and maximal pulse rate during exercise [141+/-18 vs. 163+/-17] (p<0.001), albeit not in maximal diastolic blood pressure [D0 113+/-13 mm Hg, D84 106+/-17 mm Hg (p<0.05) vs. D0 112+/-13 mm Hg, D84 104+/-15 mm Hg (p<0.05)]. The patient's own perception of the maximal effort (Borg scale) was not significantly different in either of the groups (placebo vs. treatment). Overall, in a population of hypertensive patients taking regular exercise, long-term treatment with bisoprolol produced no significant changes in the duration of peak effort, maximal workload, or the effort perceived by the patients themselves. The effects of regular exercise were comparable in both groups (bisoprolol or nitrendipine). Because previous studies have shown that dihydropyridines do not modify exercise performance in hypertensive patients, it may be concluded that the antihypertensive therapy with bisoprolol is well tolerated in a population of active hypertensive patients during dynamic exercise.

Adolescent↗

Effects of physical activity in mild to moderate COPD: a systematic review.

Pulmonary rehabilitation has become an evidence-based treatment for patients with severe chronic obstructive pulmonary disease (COPD). However, large numbers of patients who suffer from mild to moderate COPD receive treatment from their general practitioners (GPs). To encourage compliance, advice given to patients in general practice should be clear, practical, and acceptable. This is particularly true of the advice that is given by GPs to improve their patients' physical condition by walking, cycling or swimming, as recommended by the Dutch College of General Practitioners in their guideline for the treatment of COPD. We performed a literature search on the effects of physical activity in patients with mild to moderate COPD on exercise tolerance, dyspnoea and quality of life (QOL). We also looked at the numbers of hospitalisation days and exacerbations, expressed as oral prednisolone courses. The literature search included Medline (1983 to 1999), EMBASE (1984 to 2000), and the Cochrane Library (2000). All hits were screened for subject and language and abstracts were selected on the basis of a protocol that included disease severity, hypothesis, outcome parameters, and control group. Review articles on physical exercise and COPD were examined and reference lists of selected articles were screened for relevant studies The broad literature search generated 4,968 articles and, after exclusion according to title and abstract, 35 original studies and 27 review articles were analysed. Of these, five original studies fitted the criteria and none of the review articles was selected. A positive influence of physical activity on exercise tolerance in mild to moderate COPD was reported in four out of five studies. There was no clear effect on dyspnoea or QOL, probably because of the low numbers of subjects. No studies that addressed the number of hospitalisation days or prednisolone courses as outcomes were included. Physical exercise training (usually as part of a package of rehabilitation) can improve the fitness of patients with mild or moderate COPD, but it has not been shown to benefit QOL or dyspnoea significantly, or indeed long-term disease progression.

Dyspnea↗

Buspirone effect on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease.

Buspirone is an anxiolytic agent that appears to have no sedative effects. The aim of this study was to assess the effects of buspirone on breathlessness and exercise tolerance in patients with chronic airway obstruction. Sixteen patients, age 56.9 +/- 17.0; forced expiratory volume in 1 s (FEV1) 1.15 +/- 0.42 l; FEV1/forced vital capacity (FVC) 50.7 +/- 15.0%; PaCO2 42.2 +/- 5.5 mm Hg; and PaO2 57.6 +/- 10 mm Hg, underwent a 6-min walking test, an incremental cycle ergometer test, an incremental treadmill walking test with self-assessment of dyspnea on Borg's scale during exercise and an assessment of respiratory drive (P 0.1), timing [inspiration time (TI)/total breathing time (Ttot)], PaO2, PaCO2, FVC, FEV1, following oral administration for 14 days of placebo or buspirone (20 mg daily) in a double-blind, cross-over randomized way. We also used the symptom check list-90-R for the assessment of subjective complaints and symptomatic behavior. A significant improvement in anxiety, depression and obsessive symptoms and complaints was noted after buspirone treatment. The P 0.1, TI/Ttot, arterial blood gases and respiratory mechanics did not change after drug treatment. There was an improvement in exercise tolerance and in the sensation of dyspnea during the buspirone period. Thus, as given in this study, oral buspirone has therapeutic potential in the treatment of dyspnea in patients with chronic lung disease.

Adult↗

Placebo-controlled trial of flosequinan in moderate heart failure. The possible importance of aetiology and method of analysis in the interpretation of the results of heart failure trials.

One hundred-thirty five patients with moderate heart failure, recruited from 18 centres, were included in a double blind, placebo controlled study to evaluate the effects of flosequinan on symptom limited tread-mill exercise tolerance. Fifteen patients in the placebo group were withdrawn from the study compared with 14 from the group given flosequinan. New York Heart Association classification was improved at week 16 in the flosequinan group relative to those randomised to placebo (P < 0.01). Depending how the other results are analysed flosequinan either appeared to have no effect on symptom limited exercise tolerance in those who completed the study; a suggestion of superiority if an analysis at endpoint is used (P = 0.09), or, if a covariate analysis at endpoint is used, then a significant improvement can be demonstrated (P = 0.04). Subset analysis suggests that the aetiology of the heart failure and the dose of diuretics used might have a major effect on the response to treatment. The best way of analysing clinical trials in heart failure is not clear as the results can be profoundly influenced by the way data from withdrawn patients are handled. The aetiology and diuretic requirement of patients may influence their response to treatment.

Adult↗

A dose response study with oral prenalterol in patients with chronic congestive cardiac failure.

Prenalterol is an orally active cardioselective beta agonist, with a long half-life. Previous studies have confirmed its inotropic activity following intravenous infusion in patients with heart failure. It has little chronotropic activity and no significant arrhythmogenicity. We have studied the response to sustained-release oral prenalterol given over four weeks at doses of 20, 40, 100, and 200 mg daily in 10 patients with New York Heart Association class II and III heart failure due to ischemic heart disease. All were in sinus rhythm and already receiving diuretics and digoxin. The drug was well tolerated and without side effects. Nine patients showed a dose-related improvement in their exercise tolerance as measured on the treadmill, up to a dose of 100 mg daily, with a significant increase in estimated oxygen uptake. There was a dose-related reduction in maximum heart rate, systolic blood pressure, and rate-pressure product during exercise, which is suggestive of a reduction in myocardial oxygen consumption. We conclude that prenalterol improves exercise tolerance without any significant cardiovascular or other side effects, and produces a clinically relevant and sustained improvement in patients with chronic heart failure. M-mode echocardiographic measurements of left ventricular dimension and function at rest did not show any change during the study.

Administration, Oral↗

Clinical predictors of marked improvement in left ventricular performance after cardiac resynchronization therapy in patients with chronic heart failure.

BACKGROUND: Previous studies have shown that cardiac resynchronization therapy (CRT) improves cardiac performance and decreases mortality and hospital admission rates. However, it is not yet clear which patients will benefit from the procedure the most. The purpose of the study was to identify the pre-implant characteristics that better predict which patients will have the best outcome after CRT. METHODS: In this observational study, 156 patients were studied with echocardiography and a 6-minute walking test at baseline and 12 months after CRT. RESULTS: After CRT, we observed an increase in left ventricular ejection fraction (+29.6%, P < .0001), a decrease in left ventricular end systolic volume (-26.4%, P < .0001), in the proportion of patients with grade 2-4 mitral regurgitation (from 47.1% to 34.0%, P = .002), and with NYHA functional class III-IV (from 83.2% to 11.6%, P < .0001), an increase in exercise tolerance (+31.1%, P < .0001). Sixty-two patients had a marked increase in left ventricular ejection fraction (> 10 units); the only independent predictor of a marked effect of CRT was the nonischemic etiology of heart failure. In patients with ischemic cardiomyopathy, the benefit on ejection fraction correlates inversely with the extension of the ischemic damage. CONCLUSIONS: CRT improves left ventricular function and exercise tolerance in the long term. The nonischemic etiology of the cardiomyopathy is the only independent predictor of a marked effect of CRT; this is probably due to the absence of ischemic, nonviable scar tissue in these patients.

Adrenergic beta-Antagonists↗

Vasodilation by urapidil in the treatment of chronic congestive heart failure in addition to angiotensin-converting enzyme inhibitors is not beneficial: results of a placebo-controlled, double-blind study.

BACKGROUND: The therapeutic benefit of an angiotensin-converting enzyme (ACE) inhibitor in combination with a different type of vasodilator is unknown. METHODS AND RESULTS: To evaluate the effects of a combined therapy on quality of life, exercise tolerance, and hemodynamic parameters, patients with severe heart failure (New York Heart Association classes III and IV, ejection fraction below 35%) who were on ACE inhibitor therapy were randomly assigned to additional double-blind treatment with urapidil (60-120 mg/d) or placebo for 12 weeks. After enrollment of 36 patients, the study was terminated early because no beneficial effects on exercise tolerance and hemodynamic parameters could be shown for the urapidil treatment, and a trend toward increased mortality of the urapidil group was observed (odds ratio, 4.92 [0.49-49.6]; P = .167). CONCLUSION: The combination of urapidil with an ACE inhibitor in the treatment of severe chronic congestive heart failure does not seem to offer any advantages over therapy with an ACE inhibitor alone and may have potentially harmful effects.

Adult↗

Pacing in hypertrophic obstructive cardiomyopathy. A randomized crossover study. PIC Study Group.

BACKGROUND: Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. METHOD: In order to evaluate the impact of pacing therapy, were performed a randomized multicentre double-blind cross-over (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment. RESULTS: After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59 +/- 36 mmHg to 30 +/- 25 mmHg (P < 0.001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2.4 to 1.4 and 1.0 to 0.4, respectively (P < 0.007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. CONCLUSION: Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment.

Adult↗