Effects of oral magnesium therapy on exercise tolerance,exercise-induced chest pain,and quality of life in patients with coronary artery disease

Previous studies have demonstrated that magnesium supplementation improves endothelial function in patients with coronary artery disease (CAD). However, the impact on clinical outcomes, such as exercise-induced chest pain, exercise tolerance, and quality of life, has not been established. In a multicenter, multinational, prospective, randomized, double-blind and placebo-controlled trial, 187 patients with CAD (151 men, 36 women; mean +/- SD age 63 +/- 10 years, range 42 to 83) were randomized to receive either oral magnesium 15 mmol twice daily (Magnosolv-Granulat, total magnesium 365 mg provided as magnesium citrate) (n = 94) or placebo (n = 93) for 6 months. Symptom-limited exercise testing (Bruce protocol) and responses given on quality-of-life questionnaires were the outcomes measured. Magnesium therapy significantly increased intracellular magnesium levels ([Mg]i) in a substudy of 106 patients at 6 months compared with placebo (35.5 +/- 3.7 vs 32.6 +/- 2.9 mEq/L, p = 0.0151). Magnesium treatment significantly increased exercise duration time compared with placebo (8.7 +/- 2.1 vs 7.8 +/- 2.9 minutes, p = 0.0075), and lessened exercise-induced chest pain (8% vs 21%, p = 0.0237). Quality-of-life parameters significantly improved in the magnesium group. These findings suggest that oral magnesium supplementation in patients with CAD for 6 months results in a significant improvement in exercise tolerance, exercise-induced chest pain, and quality of life, suggesting a potential mechanism whereby magnesium could beneficially alter outcomes in patients with CAD.     

Correlation of the exercise ST/HR slope with anatomic and radionuclide cineangiographic findings in stable angina pectoris

A rate-related change in ST-segment depression with exercise (ST/HR slope) of 6.0 microV/beat/min or more has been proposed as an accurate predictor of 3-vessel coronary artery disease (CAD). To further assess the accuracy and functional correlates of this method, exercise electrocardiograms were compared with radionuclide rest and exercise left ventricular (LV) ejection fraction (EF) and angiography in 35 patients with stable angina. The ST/HR slope was significantly increased in patients with 3-vessel CAD. An ST/HR slope of 6.0 or more identified 3-vessel CAD with a sensitivity of 89% and specificity of 88%. The predictive value for 3-vessel CAD was 73% owing to the presence of 3 false-positive slopes. The patients from whom these slopes were derived had functionally severe 2-vessel CAD, with an average decrease in exercise LVEF of 13%. Two of these 3 had additional left main CAD and the third has unsuspected additional aortic regurgitation. For the entire group, the exercise ST/HR slope was linearly related to the exercise change in LVEF (r = -0.55, p less than 0.001). Mean exercise change in LVEF for stable angina patients with ST/HR slopes of 4.5 or more was significantly different from that for patients with lower ST/HR slopes (-12 +/- 1% vs + 2 +/- 2%, p less than 0.0001). Thus, the ST/HR slope is both sensitive and specific for the identification of 3-vessel CAD, and high ST/HR slopes in patients with less extensive anatomic disease may predict functionally severe ischemia.     

Effects of verapamil and nifedipine on blood pressure during rest and exertion and on left ventricular hypertrophy]

The effects of 6 months treatment with nifedipine 20 mg SR (N) or verapamil 240 mg SR (V) on rest and exercise BP and left ventricular mass (LVM) and function were evaluated in 31 essential hypertensive patients (mean age: 54, 19 males, 12 females), never treated with calcium antagonist. After a 15 days placebo run in, BP was measured at rest and during a maximal bicycle exercise test (stages: 30 watts, 3 min). 2D guided M mode echocardiography and pulsed Doppler allowed assessment of left ventricular mass (Devereux's formula) and function (fractional shortening FS, peak early (E) and late (A) velocities of LV filling). Patients were randomised to N (n = 18) or V (n = 13) and reassessed 6 months later. All echo-Doppler recordings were read blindly by 2 observers. Results: rest BP was similarly reduced in both groups (V: 148 +/- 12/88 +/- 5 vs 162 +/- 10/101 +/- 7; N: 148 +/- 15/90 +/- 7 vs 170 +/- 14/101 +/- 8), as well as exercise maximal BP (V: 224 +/- 32/93 +/- 11 vs 243 +/- 21/104 +/- 11; N: 206 +/- 27/90 +/- 10 vs 231 +/- 17/97 +/- 8). The duration of exercise was significantly increased with V (15 +/- 5 min vs 12 +/- 4, p < 0.05) and insignificantly decreased with N (11 +/- 2 vs 12 +/- 3). Left ventricular mass was higher in V group at entry and was significantly more reduced with V (250 g +/- 74 vs 302 g +/- 92, p < 0.01) than with N (225 g +/- 54 vs 234 g +/- 69).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-induced ST-segment depression: imbalance between myocardial oxygen demand and myocardial blood flow

OBJECTIVE: ST-segment depression is believed as a common electrocardiographic sign of myocardial ischemia during exercise testing. Ischemia is generally defined as oxygen deprivation due to reduced perfusion. However, the exact relationship of the ischemic definition to ST-segment depression remains unclear. This study was conducted to evaluate the correlation between myocardial oxygen demand and myocardial blood flow (MBF) when ischemic (horizontal or downsloping) ST-segment depression of > or = 0.1 mV 80 ms after the J point developed during low-level exercise. METHODS AND RESULTS: Seventy-two patients with angiographically proven coronary artery disease (CAD) and 9 healthy volunteers underwent exercise positron emission tomography (PET). Myocardial oxygen demand was defined as a rate-pressure product (RPP, heart rate x systolic blood pressure) during exercise and MBF was quantified by nitrogen-13 ammonia perfusion PET. The myocardial demand-supply balance (MDSB) index was calculated from the MBF ratio (values during exercise/values at rest) against the RPP ratio (values during exercise/values at rest). The MDSB index was significantly lower in patients with ischemic ST-segment depression than in patients with non-ischemic ST depression and healthy volunteers (0.82 +/- 0.16 vs. 1.02 +/- 0.17, p < 0.0001 and vs. 0.99 +/- 0.14, p = 0.0109). Further, the presence of inadequate increase in MBF of < or = 10% (2 SD below the mean % value of healthy volunteers) during exercise in regional myocardium perfused by stenotic CAD significantly correlated with exercise-induced ischemic ST-segment depression (p = 0.0105). CONCLUSIONS: Our study could demonstrate that exercise-induced ischemic ST-segment depression is associated with myocardial ischemia due to exercise-induced imbalance between myocardial oxygen demand and global and regional MBF supply in patients with proven CAD.     

Relationship between bronchial response to respiratory heat exchange and nonspecific airways reactivity in asthmatic patients

In this study we have examined the relationship between the bronchial response to inhaled histamine and the bronchial response to breathing cold air at rest in nine control subjects and nine patients with asthma. Dried warm air (mean temp: +/- 1SD: 25.4 +/- 1.6 degrees C) and cold air (-19.7 +/- 2.6 degrees C) were breathed for 10 minutes each during quiet breathing at rest prior to as well as during both measurements of forced expired spirograms and the phase 3 slope of the single-breath oxygen test (delta N2/L). Subjects were also challenged with inhaled aerosolized histamine to determine the concentration required to reduce the forced expired volume in one second (FEV1) by 20 percent (PC20). Both asthmatic and control subjects had significantly greater respiratory heat exchange breathing cold as compared to warm air (p less than 0.01 in both cases). Control subjects did not change FEV1 or delta N2/L breathing cold air. Asthmatic patients increased delta N2/L from a mean warm air value of 2.41 +/- 1.31% N2/L to a mean cold air value of 5.39 +/- 4.55% N2/L (p less than 0.05). There was a significant linear correlation between the percent increase in delta N2/L from warm to cold air and 1/log10PC20 (r = -0.97, p less than 0.001) and also the percent decrease in FEV1 and log PC20 (r = -0.76, p less than 0.03) in the asthmatic patients. We conclude that cold air-induced alterations in ventilation/distribution and expired flow rates in asthmatic patients are related to pre-existing nonspecific airways reactivity.     

Carnitine status, plasma lipid profiles, and exercise capacity of dialysis patients: effects of a submaximal exercise program

Carnitine status, blood lipid profiles, and exercise capacity were evaluated in a combined group of hemodialysis (N = 4) and continuous ambulatory peritoneal dialysis (N = 6) patients before and after an 8-week submaximal exercise program. Maximal aerobic capacity (VO2max) was only 18.5 +/- 5.9 (mean +/- SD) mL O2/kg/min, well below the expected 30 to 35 mL O2/kg/min for age-matched sedentary controls. Plasma short-chain acylated carnitine levels, which were two to three times normal values, were reduced after the exercise program, but the long-chain acylcarnitines were significantly reduced during acute exercise. Muscle biopsies of the vastus lateralis were performed at rest in five patients prior to and after the 8-week exercise program. Total carnitine in skeletal muscle was 3.09 (.076 SD) mumol/g ww, with only 11.3% acylated prior to the exercise program, which was much lower than the 4.25 +/- 1.27 mumol/g ww, with 28.5% acylated in a group of healthy athletic subjects (N = 28). Muscle free carnitine concentrations decreased significantly following the 8-week training period, with only a slight reduction in total carnitine. The percent of acylated carnitine was therefore significantly increased (P less than 0.05) from 11.3% to 25.2% after the experimental period. Pretraining carnitine palmitoyl transferase activity at rest was 0.57 +/- 0.28 nmol palmitoyl carnitine formed/5 min/mg mitochondrial protein, which was not changed by exercise training v 1.80 +/- 0.51 nmol/5 min/mg protein in 28 healthy normals (P less than 0.001). Free fatty acid concentrations were reduced significantly during acute exercise as a result of the exercise training program whereas other plasma lipids were not altered. (ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes in left ventricular diastolic performance

Previous studies show that the radionuclide-derived indices of left ventricular (LV) diastolic performance are abnormal at rest in many patients with coronary artery disease (CAD), even in those with normal resting ejection fraction (EF) and no prior myocardial infarction. This study examined the age-related changes in LV peak filling rate and time to peak filling rate in 65 subjects between the ages of 20 and 75 years with a low likelihood of CAD. All subjects had normal resting EF (greater than or equal to 50%), and none had prior infarction. There was a significant age-related decline in resting peak filling rate (r = -0.47, p less than 0.001) and exercise peak filling rate (r = -0.52, p less than 0.001), but no age-related effect in the time to peak filling rate. Of the 29 subjects less than 50 years of age, 26 (90%) had resting peak filling rate greater than or equal to 2.5 EDV/sec (3.1 +/- 0.6, mean +/- SD) compared to 17 of 36 subjects (47%) greater than or equal to 50 years of age (2.6 +/- 0.6) (p = 0.002). In a subgroup of 28 subjects with a history of hypertension, the age-related effect was more marked than in the remaining 37 subjects without such a history (r = -0.66 vs -0.33). Thus, the peak filling rate at rest and during exercise decreases with advancing age; the high frequency of observed abnormality in the peak filling rate at rest in patients with CAD may conceivably be related in part to age differences between patients with CAD and the control group.     

Correlation of changes in quality of life after lung volume reduction surgery with changes in lung function, exercise, and gas exchange

STUDY OBJECTIVES: To evaluate correlations between improvement in quality of life (QOL) in patients with severe COPD before and after they undergo lung volume reduction surgery (LVRS) with changes in pulmonary function tests, gas exchange, exercise performance, and alterations in medical management. DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Forty-two patients (mean [+/- SD] age, 56+/-8 years; 53% women) with severe airflow obstruction (FEV(1), 0.62+/-0.2 L), and moderate to severe hyperinflation (total lung capacity [TLC], 6.9+/-1.7 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Measurements of lung function, symptom-limited cardiopulmonary exercise testing, the total distance the patient was able to walk in 6 min in a corridor, and sickness impact profile (SIP) scores were made before and 3 months after LVRS. SIP scores are inversely proportional to the level of function and QOL. RESULTS: Compared to baseline, FEV(1) increased (0.87+/-0.3 vs. 0.62+/-0.2 L, respectively; p<0.01) while residual volume significantly decreased (3.2+/-1.8 vs. 6.3+/-1.2 L, respectively; p<0.004) at 3 months post-LVRS. On cardiopulmonary exercise testing, values increased from baseline to post-LVRS for total exercise time (9.0+/-2.2 vs. 6.0+/-1.5 min, respectively; p = 0.045), maximum oxygen uptake (VO(2)) (16+/-3 vs. 11+/-2 mL/kg/min, respectively; p = 0.01), and maximum minute ventilation (VE) (33+/-9 vs. 28+/-5 L/min, respectively; p = 0.03). The percentage change in the oxygen cost of breathing (VO2/VE ratio) from low to high workloads during exercise was significantly lower after LVRS (p = 0.002). There was no significant change in oxygenation after LVRS (PaO(2)/fraction of inspired oxygen, 331+/-27 vs. 337+/-39, respectively; p = 0.76), but PaCO(2) tended to be lower (41+/-9 vs. 48+/-6 mm Hg, respectively; p = 0.07). Overall SIP scores were significantly lower after LVRS than before (8+/-4 vs. 15+/-2, respectively; p = 0.002). Changes in SIP scores correlated with the change in VO2/VE ratio from low to high workloads, with patients having the smallest changes in VO2/VE ratio having the smallest changes in SIP scores after LVRS (r = 0.6; p = 0.01). Improved or lower SIP scores also tended to correlate with a reduction in residual volume/TLC ratio (r = 0.45; p = 0.09), and there was a linear correlation with a statistically significant Pearson r value with decreased steroid requirements (r = 0.7; p = 0.001). Moreover, changes in psychological SIP subscore tended to correlate with diminished oxygen requirements post-LVRS (r = 0.45; p = 0.09). However, there was no significant correlation between changes in SIP scores and routine measurements of lung function, exercise performance, or gas exchange. CONCLUSION: There is an association between an improvement in QOL and reduced hyperinflation after LVRS. Reduced hyperinflation may lead to more efficient work of breathing during exercise and, therefore, to an increased ability to perform daily activities. Changes in QOL scores correlate best with behaviorally based variables that directly affect the patient's well-being, such as systemic steroid administration.     

Total lung capacity: single breath methane dilution versus plethysmography in normals

OBJECTIVE AND BACKGROUND: Methane is an inert tracer gas used to obtain TLC estimates during single breath diffusion capacity (DL(CO)) measurements. The aim of this study was to assess the accuracy of methane dilution TLC in normal subjects undergoing single breath diffusion capacity measurements using plethysmography as the gold standard comparison method. METHODS: Fifty non-smoking adults underwent lung function testing. Total lung volume was obtained by both plethysmography and methane dilution during a single breath DL(CO) measurement. Deming regression and the concordance correlation coefficient, r(ccc), were used to determine agreement between methods for TLC. Bias was the mean difference between methods and limits of agreement were the mean difference between methods +/- 1.96 (SD). All values are mean +/- SD unless otherwise stated. RESULTS: Plethysmography and methane dilution TLC values were not significantly different. The r(ccc) was 0.87 (95% confidence interval (CI) 0.78-0.92). Deming regression revealed a slope of 0.93 (P = 0.17, H(o): beta = 1.0; 95% CI 0.84-1.03) and a y-intercept of 0.20 (P = 0.39, H(o): alpha = 0; 95% CI -0.27-0.70). The bias was 0.11 L favouring plethysmography. Limits of agreement varied as 0.11 +/- 0.92 L. CONCLUSIONS: There is statistical agreement between methods suggesting the average TLC by methane could substitute for plethysmography in normals at the population level. At the individual level, a normal methane dilution value indicates a normal TLC whereas values below the normal range should be validated using plethysmography.     

Comparison between thallium-201 and technetium-99m methoxyisobutyl isonitrile defect size in single-photon emission computed tomography at rest, exercise and redistribution in coronary artery disease.

Defect size on myocardial tomograms was measured in 30 patients who underwent 2 separate studies, 1 with thallium-201 (TI-201), the other with technetium-99m-methoxyisobutyl isonitrile (MIBI). A group of 15 patients with myocardial infarction was studied at rest and received both tracers on the same day. The other 15 patients had documented coronary artery disease. They were were given injections of TI-201 at peak exercise and underwent imaging immediately after exercise and again 4 hours later. They then received a dose of MIBI for imaging at rest. A week later they underwent a second exercise test with the same work load and received a second dose of MIBI. Defect size on single-photon emission computed tomographic images was measured and repeated twice. Results were expressed in percentage of the volume of the whole myocardium. Reproducibility of the defect size measurement was high for TI-201 (r = 0.978; SEE = 1.59) as well as for MIBI (r = 0.981; SEE = 0.80). In patients with coronary artery disease the mean size of the defects was significantly larger with TI-201 than with MIBI at exercise (6.7 +/- 5.2 vs 4.6 +/- 5.2%, respectively, p less than 0.05) and at redistribution (5.1 +/- 4.4 vs 2.8 +/- 3.2%, respectively, p less than 0.05), where no difference was seen in patients with myocardial infarction studied only at rest (11.2 +/- 10.4 vs 12.0 +/- 11.5%, respectively, p = not significant). Smaller MIBI defect sizes, when compared with TI-201, in the exercise and redistribution studies were not due to technical artefacts since there was no difference when they were compared at rest.     

Relation of B-type natriuretic peptide levels before and after exercise and functional capacity in patients with idiopathic dilated cardiomyopathy

Although much is known about the value of B-type natriuretic peptide (BNP) at rest, the significance of the responsiveness of BNP during exercise in patients with chronic heart failure (HF) without coronary artery disease remains to be established. A role of BNP release during exercise in the functional disability of patients with chronic HF and idiopathic dilated cardiomyopathy (IDC) was hypothesized. One hundred five consecutive patients with an established diagnosis of HF and IDC who underwent symptom-limited cardiopulmonary exercise testing were studied. BNP was measured immediately before exercise and within 1 minute of the end of exercise. BNP at rest increased significantly at peak exercise (median from 66.5 (first, third quartiles 18, 168) to 72.0 pg/ml (26, 208), p <0.001), but BNP response was not uniform. BNP response increased in 63% of patients, did not change in 22%, and decreased in 15%. BNP at rest and BNP response showed an inverse correlation (p <0.001, r = -0.523). Aging and low left ventricular ejection fraction were independent predictors of higher BNP levels at rest, but lower BNP response. Beta-blocker therapy did not influence BNP response. BNP at rest correlated negatively with functional capacity (p <0.001, r = -0.516), whereas BNP response correlated positively (p = 0.002, r = 0.326). Patients with BNP release (vs patients without) had higher maximum oxygen consumption (19.2 +/- 5.1 vs 15.9 +/- 3.6, p <0.001), better functional capacity (59 +/- 13% vs 50 +/- 15%, p = 0.002), and lower minute ventilation/carbon dioxide production slope (33.6 +/- 4.8 vs 36.5 +/- 7.7, p = 0.026) independent of other clinical parameters. In conclusion, BNP release during exercise could be a determinant of functional capacity in patients with chronic HF and IDC.     

Response of the right ventricle to exercise in isolated mitral stenosis

Eight patients in sinus rhythm, with varying degrees of isolated mitral stenosis (mitral valve area 0.6 to 1.3 cm2 and total pulmonary vascular resistance 5.0 to 17.5 U-m2), underwent supine rest and symptom-limited exercise radionuclide ventriculography to determine right ventricular (RV) and left ventricular ejection fraction (EF). Cardiac catheterization with hemodynamic measurements at rest and at peak exercise was performed within 24 hours of radionuclide ventriculography. Four of the 8 patients underwent corrective mitral surgery resulting in normal mean pulmonary artery pressures and total pulmonary vascular resistance at rest. These 4 patients had repeat radionuclide ventriculography at rest and during exercise 1 to 2 months after surgery. Preoperatively, all 8 patients had an abnormal exercise RVEF response (mean change +/- standard deviation [SD], -5.0 +/- 4.5%), coincident with an increase in mean pulmonary artery pressure during exercise (mean change, 15 +/- 5.0 mm Hg). The change in RVEF from rest to exercise, corrected for duration of exercise, correlated with peak exercise mean pulmonary artery pressure (r = -0.71, p = 0.05), as well as total pulmonary vascular resistance at rest (r = -0.82, p = 0.02). Postoperatively, all 4 patients who underwent surgical correction showed a normal RVEF response during exercise (mean change +/- SD, +6.8 +/- 4.0%). Thus, in patients with acquired mitral stenosis and no coronary artery disease (1) loading conditions and not contractility are prime determinants of RV exercise response, and (2) an exercise-induced decrease in RVEF may be a sensitive marker for increased total pulmonary vascular resistance and pulmonary hypertension.     

Supine bicycle echocardiography improved diagnostic accuracy and physiologic assessment of coronary artery disease with the incorporation of intermediate stages of exercise.

OBJECTIVES: The purpose of this work was to assess whether the incorporation of intermediate stages during supine bicycle exercise echocardiography (BEE) improves the accuracy of detection of coronary artery disease (CAD) through the evaluation of a biphasic response. BACKGROUND: Exercise echocardiography allows cardiac imaging throughout exercise. METHODS: Exercise echocardiography was performed in 104 patients (mean age 57 +/- 11 years, 37 women), 91 of whom underwent coronary angiography. The BEE protocol started at 25 W with increments of 25 W every 3-min stage. Images were digitized at rest, 25 W, 50 W, and peak exercise. Two experienced observers and 1 less experienced observer interpreted rest and peak exercise images, with and without the intermediate stages. RESULTS: Imaging during intermediate stages improved the sensitivity for detection of all individual vessel stenoses (78% vs. 58%, p < 0.001) and patients overall (94% vs. 74%, p = 0.001). The specificity was unchanged (all vessels: 83% vs. 81%, all patients: 64% vs. 60%). A change in left ventricular end-systolic volume from intermediate stage to peak exercise of >10% predicted CAD (sensitivity 94%, specificity 74%) and was more marked than changes observed from rest to peak exercise. The severity of coronary stenosis related to the double product achieved at the onset of ischemia during exercise (r = -0.61, p < 0.001) better than that at maximal exercise (r = -0.31, p < 0.01). CONCLUSIONS: During BEE, the acquisition and interpretation of intermediate stages of exercise in addition to peak exercise improves the detection of CAD and allows a better physiologic evaluation of the severity of coronary stenosis.     

Left ventricular functional recovery from exercise in normals and patients with coronary heart disease

Little information is available regarding left ventricular (LV) functional recovery from treadmill exercise. Accordingly, we used a recently described ultrasound index of LV function, the isovolumic index (IVI), to assess LV performance before and after exercise in 9 normal middle-aged men and 12 male patients with coronary artery disease (CAD). The IVI was measured at rest and at each minute for at least 10 min after completion of the Bruce protocol; normals had maximal tests and CAD patients had symptom limited studies. At rest the IVI value for normals was 26.2 +/- 2.1 (SD) and it was 43.5 +/- 8.2 for CAD patients (p less than 0.001); isovolumic times were longer in CAD patients (137 +/- 26 vs. 89 +/- 8 ms, p less than 0.001). The rate of recovery from exercise did not differ between normals and CAD patients. We conclude that despite depression of resting LV performance in CAD patients, the time course of functional recovery of the left ventricle from exercise is not different from normal subjects.     

Exercise testing in asymptomatic or minimally symptomatic aortic regurgitation: relationship of left ventricular ejection fraction to left ventricular filling pressure during exercise

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equal to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. Group 1 patients also had a higher mean rest ejection fraction (0.64 +/- 0.08 vs 0.49 +/- 0.13, p less than 0.01, higher exercise ejection fraction (0.63 +/- 0.10 vs 0.40 +/- 0.18, p less than 0.01), lower end-systolic volume (38 +/- 13 vs 79 +/- 36 ml/m2, p less than 0.01) and higher peak oxygen uptake (24.9 +/- 5.1 vs 16.6 +/- 4.9 ml/kg/min, p less than 0.01) than group 2 patients. However, the two groups had similar cardiothoracic ratios, changes in ejection fractions with exercise, and rest and exercise regurgitant indexes. Using multiple regression analysis, the best correlate of the exercise PAWP was peak oxygen uptake (r = -0.78, p less than 0.01). No other measurement added significantly to the regression. When peak oxygen uptake was excluded, rest and exercise ejection fraction also correlated significantly (r = -0.62 and r = -0.60, respectively, p less than 0.01). Patients with asymptomatic or minimally symptomatic severe aortic regurgitation have a wide spectrum of cardiac performance in terms of the PAWP during exercise. The absolute rest and exercise ejection fraction and the level of exercise achieved are noninvasive variables that correlate with exercise PAWP in aortic regurgitation, but the change in ejection fraction with exercise by itself is not.     

Effect of enhanced external counterpulsation on resting oxygen uptake in patients having previous coronary revascularization and in healthy volunteers

This study analyzed the acute effects of enhanced external counterpulsation (EECP) on oxygen uptake (VO2) at rest in adults with symptomatic coronary artery disease (CAD) compared with healthy volunteers. EECP therapy increases exercise tolerance in patients with refractory angina pectoris. This may be attributed, at least in part, to a training effect, but measurement of VO2 during an EECP treatment session has not been previously reported. We measured VO2 continuously in 20 adults during a single treatment session of EECP, including 10 subjects with previous coronary revascularization who were referred for EECP therapy for refractory angina, and 10 healthy, sedentary volunteers. VO2 was measured for 10 minutes before EECP, during a 30-minute EECP treatment session, and for 10 minutes after cessation of EECP treatment. Patients with CAD were older (65.9 +/- 12 vs 38.5 +/- 7 years, p = 0.002) and had a higher body mass index (32.0 +/- 10.0 vs 25.5 +/- 3.0 kg/m2, p = 0.027) and percent body fat (37 +/- 7% vs 21+/-9%, p = 0.006). VO2 at rest, although slightly lower in the CAD group, was not significantly different (2.75 +/- 0.54 vs 3.19 +/- 0.51 ml/kg/min, p = 0.09). The 2 groups demonstrated a small, sustained increase in VO2 during EECP treatment (CAD +0.66 +/- 0.56 ml/kg/min, p < 0.005; healthy +0.72 +/- 0.40 ml/kg/min, p < 0.001; CAD vs healthy, p = 0.13), which returned to baseline levels during recovery. In conclusion, VO2 at rest is increased to the same degree during an EECP treatment session in healthy subjects and symptomatic patients with CAD. This effect may contribute to the increased exercise tolerance of patients with refractory angina after receiving EECP therapy.     

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.     

Improvement in mitral flow dynamics during exercise after percutaneous transvenous mitral commissurotomy. Noninvasive evaluation using continuous wave Doppler technique

Evaluation of mitral flow dynamics during exercise is critically important in patients who receive percutaneous transvenous mitral commissurotomy (PTMC) because limited mitral flow during exercise provokes hemodynamic deterioration and involves cardiogenic symptoms in patients with mitral stenosis. To examine mitral flow dynamics during exercise, we applied continuous wave Doppler technique in 20 patients with mitral stenosis. Exercise Doppler study was performed 2 days before and 5 days after PTMC. PTMC increased mitral valve area from 1.0 +/- 0.3 (mean +/- SD) to 1.9 +/- 0.5 cm2 and decreased mean transmitral pressure gradient from 8 +/- 2 to 4 +/- 1 mm Hg at rest. Moreover, PTMC decreased mean transmitral pressure gradient from 21 +/- 6 to 11 +/- 4 mm Hg at submaximal exercise. The extent of an increase in mitral valve area by PTMC correlated with a decrease in the mean transmitral pressure gradient at the submaximal exercise (r = -0.76, p less than 0.01) and that at rest (r = -0.52, p less than 0.05). Heart rate after PTMC during exercise was significantly lower than that before PTMC, indicating that the compensatory mechanism (tachycardia) to increase cardiac output during exercise is less necessary after PTMC. Thus, we conclude that the mitral flow dynamics during exercise is improved, as well as the resting mitral flow dynamics 5 days after PTMC, and that exercise Doppler study enabled us to make a noninvasive evaluation of the mitral flow dynamics in patients who receive PTMC.     

Prolonged oxygen kinetics during early recovery from maximal exercise in adult patients with cystic fibrosis

Study objectives: To explore the significance of oxygen kinetics during early recovery after maximal cardiopulmonary exercise testing (CPET) in the assessment of functional capacity and severity of the disease in cystic fibrosis (CF) patients. PARTICIPANTS: Eighteen patients with CF (9 male/9 female; mean +/- SD age, 23 +/- 13 years) and 11 healthy subjects (3 male/8 female; mean age, 29 +/- 4 years) underwent maximum CPET on a treadmill. Breath-by-breath analysis was used for measuring oxygen consumption (VO(2)), carbon dioxide production, and ventilation. Maximum VO(2) (VO(2)peak) and the first-degree slope of VO(2) decline during early recovery (VO(2)/t-slope) were calculated. To assess the severity of the disease, we used standard indexes like FEV(1) (% predicted), VO(2)peak, and a widely accepted system of clinical evaluation, the Schwachman score (SS). RESULTS: VO(2)/t-slope was significantly lower in CF patients compared to healthy subjects (0.61 +/- 0.31 L/min/min vs 1.1 +/- 0.13 L/min/min; p < 0.01) and was closely correlated to FEV(1)(r = 0.90, p < 0.001), VO(2)peak (r = 0.81, p < 0.001), and the SS (r = 0.81, p < 0.001). The multivariate analysis showed that the only independent predictor of the SS is the VO(2)/t-slope. CONCLUSION: We conclude that in CF patients, the prolonged oxygen kinetics during early recovery from maximal exercise is related to the disease severity.     

Helium-hyperoxia, exercise, and respiratory mechanics in chronic obstructive pulmonary disease

RATIONALE: Hyperoxia and normoxic helium independently reduce dynamic hyperinflation and improve the exercise tolerance of patients with chronic obstructive pulmonary disease (COPD). Combining these gases could have an additive effect on dynamic hyperinflation and a greater impact on respiratory mechanics and exercise tolerance. OBJECTIVE: To investigate whether helium-hyperoxia improves the exercise tolerance and respiratory mechanics of patients with COPD. METHODS: Ten males with COPD (FEV(1) = 47 +/- 17%pred [mean +/- SD]) performed randomized constant-load cycling at 60% of maximal work rate breathing air, hyperoxia (40% O(2), 60% N(2)), normoxic helium (21% O(2), 79% He), or helium-hyperoxia (40% O(2), 60% He). MEASUREMENTS: Exercise time, inspiratory capacity (IC), work of breathing, and exertional symptoms were measured with each gas. RESULTS: Compared with air (9.4 +/- 5.2 min), exercise time was increased with hyperoxia (17.8 +/- 5.8 min) and normoxic helium (16.7 +/- 9.1 min) but the improvement with helium-hyperoxia (26.3 +/- 10.6 min) was greater than both these gases (p = 0.019 and p = 0.007, respectively). At an isotime during exercise, all three gases reduced dyspnea and both helium mixtures increased IC and tidal volume. Only helium-hyperoxia significantly reduced the resistive work of breathing (15.8 +/- 4.2 vs. 10.1 +/- 4.1 L . cm H(2)O(-1)) and the work to overcome intrinsic positive end-expiratory pressure (7.7 +/- 1.9 vs. 3.6 +/- 2.1 L . cm H(2)O(-1)). At symptom limitation, tidal volume remained augmented with both helium mixtures, but IC and the work of breathing were unchanged compared with air. CONCLUSION: Combining helium and hyperoxia delays dynamic hyperinflation and improves respiratory mechanics, which translates into added improvements in exercise tolerance for patients with COPD.