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Pulmonary arterial hypertension has a poor prognosis quoad vitam et valitudinem. Herein, we report on a middle-aged woman affected by idiopathic pulmonary arterial hypertension whose quality of life and exercise tolerance improved remarkably after a six-month course of treatment with the long-acting phosphodiesterase-5 inhibitor tadalafil.
OBJECTIVE: Left atrial volume (LAV) is a powerful predictor of outcome in patients with chronic heart failure (CHF) independently of symptomatic status, age and left ventricular (LV) function. It is unknown whether LAV provides independent and incremental information compared with exercise tolerance parameters. METHODS: 273 patients with CHF (mean (SD) 62 (9) years; 13% female) prospectively underwent echocardiography and exercise testing with maximal oxygen consumption (Vo(2)). The primary end point was composite and included cardiac death, hospitalisation for worsening heart failure or cardiac transplantation. RESULTS: At Cox proportional hazard analysis, LAV normalised for body surface area (LAV/BSA) was strongly associated with mortality (hazard ratio (HR) = 1.027 (95% CI 1.018 to 1.04), p<0.001). The predictive value of LAV/BSA was independent of Vo(2) and LV ejection fraction (EF) (HR = 1.014 (1.002 to 1.025), p = 0.02; HR = 0.95 (0.91 to 0.99), p = 0.02; HR = 0.89 (0.82 to 0.98), p = 0.02 for LAV/BSA, EF and Vo(2), respectively). Receiver operator characteristic (ROC) curve analysis identified the best cut-off values for prediction of the end point. LAV/BSA >63 ml, EF <30% and Vo(2) <16 ml/kg/min were considered to be risk factors. Patients with three risk factors had an HR of 38 (95% CI 11 to 129) compared with patients with no risk factors. CONCLUSION: LAV provides powerful prognostic information incrementally and independently of Vo(2). LAV, EF and Vo(2 )can be used to build a risk prediction model, which can be used clinically.
An exercise tolerance test (ETT) is often performed to identify patients for early discharge after observation for acute chest pain, but the safety of this strategy is unproven. We prospectively studied 276 low-risk patients who underwent an ETT within 48 hours after presentation to the emergency department with acute chest pain. The ETT was considered negative if subjects achieved at least stage I of the Bruce protocol and the electrocardiogram showed no evidence of ischemia. There were no complications associated with ETT performance. The ETT was negative in 195 patients (71%); there was no identifiable subsets of patients at very low probability of an abnormal test. During the 6-month follow-up, patients with a negative ETT had fewer additional visits to the emergency department (17% vs 21%, respectively; p < 0.05) and fewer readmissions to the hospital (12% vs 17%; p < 0.01) than those with positive or inconclusive ETTs. No patient with a negative ETT died and only 4 patients with a negative ETT experienced a major cardiac event (myocardial infarction, coronary angioplasty, or bypass) within 6 months. Among these 4 patients, only 1 had an event within 4 months. In conclusion, our results suggest that ETT can be safely used to identify patients at low risk of subsequent events. Patients without a clearly negative test are at increased risk for readmission and cardiac events, and should be reevaluated either during the same admission or shortly after discharge.
Naftidrofuryl enhances oxidative phosphorylation and might therefore be expected to improve exercise tolerance and breathlessness in advanced chronic bronchitis. This hypothesis was tested in a four-week placebo-controlled trial in 11 bronchitic patients. Seven patients completed the study. There was no evidence of any benefit from naftidrofuryl either subjectively or after a 12-minute walking test.
Myophosphorylase deficiency [McArdle's disease (MD)] produces a defect in muscle glycogenolysis in which muscular work is limited by delivery of external sources of substrate, primarily glucose and nonesterified fatty acids, to meet energy demands associated with exercise. In the present study, we evaluated an unusual patient with both MD and non-insulin-dependent diabetes mellitus. We hypothesized that insulin resistance would limit transport of extracellular glucose to skeletal muscle during exercise, resulting in impaired exercise performance that was reversible by insulin infusion. The effect of a hyperinsulinemic "euglycemic" clamp on exercise tolerance was evaluated by in vivo 31P-magnetic resonance spectroscopy as well as total work performed. We observed that insulin infusion significantly increased the rate of systemic glucose utilization (P < 0.01) and also significantly decreased the ratio of inorganic phosphate to phosphocreatine (P < 0.001) during forearm exercise compared with the control study. Insulin clamp was also associated with an increase in total work performed (56%) during exercise. Our findings demonstrate that resistance to the biological actions of insulin, as occurs in type II diabetes mellitus, leads to a defect in glucose transport that limits the availability of extracellular glucose to exercising muscle. In our subject with a substrate-limited skeletal muscle metabolism (MD), reversal of this defect in insulin-dependent glucose transport by a hyperinsulinemic euglycemic clamp was associated with significant improvement in magnetic resonance spectroscopy parameters of skeletal muscle metabolism as well as exercise performance.
BACKGROUND: Trimetazidine has been shown to improve anginal symptoms without altering hemodynamic variables in patients with coronary artery disease. The aim of this study was to compare the effect of trimetazidine and atenolol upon symptoms, resting left ventricular filling dynamics and exercise tolerance. METHODS: Sixteen patients (3 males, 13 females, mean age 62 +/- 7 years) were randomized to receive trimetazidine for 2 weeks (20 mg 3 times daily) or atenolol (100 mg daily), according to a double-blind, randomized, cross-over, placebo-controlled design. At the end of each treatment period patients underwent symptom-limited exercise testing, an echocardiogram and a Doppler assessment of transmitral flow pattern. Daily life anginal symptoms were annotated on a diary throughout the study. Two patients discontinued trimetazidine because of severe palpitations and only 14 patients completed the study. RESULTS: Atenolol significantly reduced the number of anginal episodes as compared to placebo or trimetazidine (0.44 +/- 0.53, 4.8 +/- 4, 2.9 +/- 4.9, p < 0.01). On atenolol, the exercise test was negative in 8 patients, but none of the patients had a negative test while on trimetazidine. Atenolol increased both time to 1 mm ST segment depression (668 +/- 213 vs 838 +/- 81 s, p < 0.05) and Doppler-derived indices of ventricular filling (E/A ratio 0.87 +/- 0.20 vs 1.21 +/- 0.26, p < 0.05). CONCLUSIONS: These results confirm the beneficial effects of atenolol in improving symptoms, exercise performance and diastolic function in syndrome X patients. Trimetazidine did not exert any significant effect on any of the analyzed variables. Since trimetazidine has been previously shown to improve myocardial ischemia in patients with overt coronary artery disease to a similar extent of beta-blockers, it is likely that other mechanisms are responsible for angina in patients with syndrome X.
A prospective study of patients with neurogenic claudication and lumbar spinal stenosis was undertaken to determine whether measurement of exercise tolerance on the treadmill would be useful in defining baseline functional status and response to surgical treatment. Twenty patients with an average age of 73 years, all of whom had intractable neurogenic claudication and radiographically confirmed severe lumbar spinal stenosis, were studied. Lumbar decompressive laminectomy was performed in all patients. Preoperatively and 2 months postoperatively, quantitative assessment of ambulation was conducted on a treadmill at 0 degree ramp incline at two different speeds: 1.2 mph and the patient's preferred walking speed. The following information was recorded: time to first symptoms, time to severe symptoms, and nature of symptoms (leg pain, back pain, or generalized fatigue). The examination was stopped after 15 minutes or at the onset of severe symptoms. In the preoperative 1.2-mph trial, the mean time to first symptoms was 2.68 minutes (median 1.31) and the mean time to severe symptoms was 5.47 minutes (median 3.42). In the postoperative trial at the same speed, 13 patients (65%) were able to walk symptom free for 15 minutes. The mean time to first symptoms was 11.12 minutes (median 15) and the mean time to severe symptoms was 11.81 minutes (median 15). Similar findings were recorded in the preferred walking-speed trials. There were no complications from the treadmill testing procedure. These findings indicate that exercise stress testing on a treadmill is a safe, easily administered, and quantifiable means of assessing baseline functional status and outcome following laminectomy in patients with symptomatic lumbar spinal stenosis.
A randomized, double-blind study of 6 months of losartan 50 mg or hydrochlorothiazide (HCTZ) 12.5 mg was performed in 40 subjects with left ventricular diastolic dysfunction (mitral flow velocity E/A ratio < 1), exercise systolic blood pressure (BP) > 200 mm Hg, systolic BP at rest < 150 mm Hg, ejection fraction > 50%, and no ischemia. Before treatment, exercise systolic BP was 213 +/- 13 mm Hg (mean +/- SD) in the 19 patients randomized to losartan and 209 +/- 11 mm Hg in the 21 patients who received HCTZ. After 6 months, exercise systolic BP was similarly reduced in patients who received losartan (197 +/- 23 mm Hg, p < 0.01) and HCTZ (191 +/- 11 mm Hg, p < 0.01). With losartan, treadmill exercise time increased from 894 +/- 216 to 951 +/- 225 seconds (p = 0.011), and quality of life improved from 15 +/- 12 to 7 +/- 10 (p = 0.015) without a change in oxygen consumption (1,895 +/- 470 to 1,954 +/- 539 ml/min, p = 0.30). With HCTZ, exercise time (842 +/- 225 to 872 +/- 239 seconds, p = 0.32) and quality of life (19 +/- 21 vs 19 +/- 24, p = 0.43) did not change, whereas oxygen consumption decreased from 2,144 +/- 788 to 1,960 +/- 706 ml/min (p = 0.022). In conclusion, in patients with diastolic dysfunction and hypertensive responses to exercise, 6 months of losartan and HCTZ blunted systolic BP during exercise. Only losartan increased exercise tolerance and improved quality of life.
OBJECTIVE: The purpose of this study was to evaluate whether a progressive cycle ergometer test (PCET) can detect minimal functional abnormalities that might indicate compromise of the pulmonary vascular bed in patients treated with praziquantel for chronic schistosomiasis who have no clinical signs of cardiopulmonary impairment. PATIENTS AND METHOD: We studied 9 patients (whose mean (SD) age was 38 (18) years and 10 control subjects aged 32 (14) years. Both groups were evaluated by spirometry and a PCET to determine maximum oxygen consumption, heart rate, minute ventilation and gas exchange. Echocardiograms were used to rule out the presence of associated heart disease. RESULTS: Lung function was similar among patients and controls. Slight decreases in maximum oxygen consumption and heart rate reserve were observed with effort during the PCET, with normal respiratory response. No echocardiographic abnormalities that might indicate the presence of pulmonary vascular occlusive disease were observed. CONCLUSIONS: The results showed that the resting lung function is normal in these patients. However, there was a slight decrease in exercise tolerance, probably related to physical detraining. The data obtained during exercise indicated that pulmonary vascular occlusive disease is unlikely in these patients. Abnormalities may appear in later stages of the disease or in patients who do not receive early medical treatment.
OBJECTIVES: The PEECH (Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure) study assessed the benefits of enhanced external counterpulsation (EECP) in the treatment of patients with mild-to-moderate heart failure (HF). BACKGROUND: Enhanced external counterpulsation reduced angina symptoms and extended time to exercise-induced ischemia in patients with coronary artery disease, angina, and normal left ventricular function. A small pilot study and registry analysis suggested benefits in patients with HF. METHODS: We randomized 187 subjects with mild-to-moderate symptoms of HF to either EECP and protocol-defined pharmacologic therapy (PT) or PT alone. Two co-primary end points were pre-defined: the percentage of subjects with a 60 s or more increase in exercise duration and the percentage of subjects with at least 1.25 ml/min/kg increase in peak volume of oxygen uptake (VO2) at 6 months. RESULTS: By the primary intent-to-treat analysis, 35% of subjects in the EECP group and 25% of control subjects increased exercise time by at least 60 s (p = 0.016) at 6 months. However, there was no between-group difference in peak VO2 changes. New York Heart Association (NYHA) functional class improved in the active treatment group at 1 week (p < 0.01), 3months (p < 0.02), and 6 months (p < 0.01). The Minnesota Living with Heart Failure score improved significantly 1 week (p < 0.02) and 3 months after treatment (p = 0.01). CONCLUSIONS: In this randomized, single-blinded study, EECP improved exercise tolerance, quality of life, and NYHA functional classification without an accompanying increase in peak VO2.
The effects of L-carnitine (900 mg, p.o. daily) on exercise performance were studied in 12 patients with stable effort angina using a multistage treadmill exercise test. Exercise tests were performed at the end of the placebo period and after 4 and 12 weeks of carnitine therapy. While 12 patients experienced angina during treadmill tests in the placebo period, 2 patients were free of angina after treatment with carnitine. The mean exercise time was 11.4 +/- 0.7 min (mean +/- SE) in the placebo period. This increased significantly to 12.2 +/- 0.5 min (p less than 0.05) after 4 weeks and 12.8 +/- 0.5 min (p less than 0.01) after 12 weeks of treatment with carnitine. The time required for 1 mm ST depression to occur was 6.4 +/- 0.9 min in the placebo period. This increased significantly to 7.6 +/- 0.9 min (p less than 0.01) after 4 weeks and 8.8 +/- 1.0 min after 12 weeks of treatment with carnitine. There was significantly less ST segment depression during the same exercise load after 12 weeks of treatment as compared with that in the placebo period (p less than 0.05). The heart rate and the pressure rate product at the same work load showed no significant difference among the 3 testing periods. The results of this study suggest that L-carnitine may improve exercise tolerance in patients with effort angina.
The relationship between rate response and exercise tolerance was studied by measuring the symptom-limited maximum treadmill time (MTT)both during fixed rate VVI pacing and during VVI + activity mode pacing (RRP) in 15 patients (mean age, 73 years) who had received rate-responsive ventricular pacemakers. Their indications were atrioventricular block, sino-atrial block, and atrial fibrillation with slow ventricular response. Basic rate was programmed to 60 ppm in both pacing modes; rate response and activity threshold were programmed to 5 and medium, respectively. The order in which the two pacing modes were tested was randomly determined. The MTT was, on average, 29% longer in RRP than in VVI mode with a mean of 12 minutes in VVI and 14.8 minutes in RRP (p less than 0.001). For the subgroup of eight patients with paced-only rhythm the average increase in MTT was 38% with a mean of 9.5 minutes in VVI and 12.8 minutes in RRP (p less than 0.01). Seven patients who showed episodes of spontaneous rhythm, increased their average MTT by 17% (mean in VVI, 14.9 minutes; in RRP, 17.1 minutes; p less than 0.02). During RRP, a significant positive correlation existed between MTT and the increase in heart rate (N = 15; r = 0.83; p less than 0.001). In 12 patients with paced-only rhythm, the pacing rate remained at the programmed basic rate when the patients were lying, sitting, and standing and increased to 86 +/- 4 ppm during casual walking, and to 101 +/- 4 ppm during jumping up and down with the pacemaker programmed to the above-mentioned parameters. The maximum pacing rate during jumping corresponded with the maximum pacing rates measured from Holter recordings during normal daily activities.
BACKGROUND: Although early improvement of haemodynamic parameters following successful cardioversion of atrial fibrillation (AF) has been well documented, the long-term benefits of sinus rhythm (SR) restoration are less obvious, mainly due to a high rate of AF relapses. AIM: To determine the impact of SR restoration and maintenance on exercise tolerance and heart failure progression in patients with persistent non-valvular AF during a one year follow-up period. METHODS AND RESULTS: We studied 104 patients (33 females, 71 males, mean age 60.4+/-7.4 years) with mild to moderate stable heart failure and persistent AF with well-controlled ventricular rate who were scheduled for cardioversion. They underwent submaximal exercise testing 24 hours before cardioversion, as well as 1 and 12 months afterwards. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol. Heart failure symptoms were assessed at the same time-points of follow-up. RESULTS: SR was presented in 66 (63.5%) patients one year after cardioversion. In patients with SR, a significant improvement in left ventricular (LV) performance, exercise capacity and heart failure symptoms was noted. There was an increase in LV fractional shortening (29.9+/-7.6% vs 35.6+/-9.3%; p<0.001), maximal workload (4.7+/-2.3 vs 8.5+/-3.0 MET; p<0.001), exercise duration (125.3+/-115.3 vs 294.7+/-216.7 sec.; p<0.001), and improvement in the NYHA functional class (p<0.001). No such changes were observed in patients who had AF relapse during follow-up or in those who had unsuccessful cardioversion. CONCLUSIONS: Successful cardioversion of persistent AF resulted in a significant improvement of exercise capacity and a decrease in heart failure symptoms during one year follow-up period only in patients who maintained SR.
BACKGROUND: The minute ventilation/carbon-dioxide output (VE/VCO2) slope as a marker of cardiac events has been established in patients with severe heart failure, but it is not known whether it is useful for other heart diseases. METHODS AND RESULTS: The present study investigated 215 patients with various heart diseases (age 59+/-11 years; ischemic heart disease, n=89; dilated cardiomyopathy, n=38; valvular disease, n=37; hypertensive heart disease, n=33; others, n=18) who underwent cardiopulmonary exercise testing to determine the VE/VCO(2) slope. Patients were divided into 2 groups according to the VE/VCO2 slope and were followed-up for 3 years. Forty-eight cardiac events (6 deaths, 42 re-hospitalizations) occurred during the observation period. Patients with a VE/VCO2 slope >34 had a significantly higher 3-year cardiac event rate (32.1%) than patients with VE/VCO2 slope <34 (18.9%, p<0.05). When patients were selected with relatively preserved peak oxygen uptake values (>16 ml . kg (-1) . min(-1)), patients with VE/VCO2 slope >34 still demonstrated a significantly higher cardiac event rate than other patients (35.0% vs 13.3%, p<0.01). CONCLUSION: The VE/VCO2 slope may be a prognostic indicator of cardiac events in a heterogeneous group of patients with heart disease, independent of exercise tolerance.
The analysis of the parameters of haemodynamics and gas exchange in connection with the tolerance of physical exercises in 57 patients with chronic ischaemic heart disease treated with Obsidan permitted to distinguish two variants of response to the exercises. The first is characterized by a greater increase of the cardiac output and by a slighter participation of the oxygen utilization coefficient and oxygen pulse in ensuring the oxygen regimen of work. The prescription of Obsidan is rational in the first variant of response to the physical exercises.
The effects of intravenous (0.4 mg) and oral pindolol (5 mg, t.i.d.) on exercise tolerance and electrocardiographic ST-segment changes were investigated in 20 patients with documented coronary artery disease (16 males and 4 females; mean age, 56.7 years). A randomized double-blind crossover design was used, and graded submaximal exercise was performed on a bicycle ergometer. Pindolol significantly decreased heart rate at rest, and during and after exercise. The time intervals before the appearance of ST depression, before anginal pain, and before the cessation of work were significantly increased after beta-adrenergic blockade, and work tolerance was enhanced, both indicating that pindolol is an effective antianginal agent. Angina appeared at a lower heart rate after pindolol. Anginal pain and cessation of work were associated with significantly less ST-segment depression after pindolol, suggesting that the relation between ST depression and myocardial ischemia is altered by beta-adrenergic blockade. The appearance and disappearance of ST-segment changes correlated closely with heart rate during placebo and pindolol treatment. Heart rate thus seems to be a major determinant of ST-segment depression during and after exercise in coronary artery disease.
The aim of this research was to assess whether the antihypertensive therapy with nifedipine, a dihydropyridine calcium-antagonist, is able to control hypertension not only at rest but also during exercise. So, 20 male hypertensive patients, mean age 48 years, were evaluated by symptom limited bicycle exercise (10 W/min) before and after 6 and 12 months of therapy with nifedipine in a slow releasing form (40-60 mg/day). Exercise tolerance significantly increased after 12 months of antihypertensive therapy with nifedipine (from 146 +/- 5 to 153 +/- 4 W, p < 0.05). Systolic and diastolic blood pressure decreased after 6 and 12 months both at rest (from 160 +/- 6/109 +/- 9 mmHg to 132 +/- 3/91 +/- 3 and 135 +/- 4/93 +/- 1 mmHg, respectively, both p < 0.001) and during exercise (at end exercise: from 238 +/- 7/121 +/- 5 mmHg to 216 +/- 6/106 +/- 3 and 213 +/- 6/107 +/- 3 mmHg, respectively, both p < 0.001). No significant changes in heart rate were observed during antihypertensive therapy both at rest and during exercise test. In conclusion, long-term antihypertensive therapy with nifedipine was effective in the control of hypertension both at rest and during physical stress. Moreover, an improvement in effort tolerance was observed in hypertensive patients.
BACKGROUND: Lung resections determine a variable functional reduction depending on the extent of the resection and the time elapsed from the operation. The objectives of this study were to prospectively investigate the postoperative changes in FEV(1), carbon monoxide lung diffusion capacity (Dlco), and exercise tolerance after major lung resection at repeated evaluation times. METHODS: FEV(1), Dlco, and peak oxygen consumption (Vo(2)peak) calculated using the stair climbing test were measured in 200 patients preoperatively, at discharge, and 1 month and 3 months after lobectomy or pneumonectomy. Preoperative and repeated postoperative measures were compared, and a time-series, cross-sectional regression analysis was performed to identify factors associated with postoperative Vo(2)peak. RESULTS: One month after lobectomy, FEV(1), Dlco, and Vo(2)peak values were 79.5%, 81.5%, and 96% of preoperative values and recovered up to 84%, 88.5%, and 97% after 3 months, respectively. One month after pneumonectomy, FEV(1) percentage of predicted, Dlco percentage of predicted, and Vo(2)peak values were 65%, 75%, and 87% of preoperative values, and were 66%, 80%, and 89% after 3 months, respectively. Three months after lobectomy, 27% of patients with COPD had improved FEV(1), 34% had improved Dlco, and 43% had improved Vo(2)peak compared to preoperative values. The time-series, cross-sectional regression analysis showed that postoperative Vo(2)peak values were directly associated with preoperative values of Vo(2)peak, and postoperative values of FEV(1) and Dlco, and were inversely associated with age and body mass index. CONCLUSIONS: Our findings may be used during preoperative counseling and for deciding eligibility for operation along with other more traditional measures of outcome.