Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure: implications for outpatient monitoring with B-type natriuretic peptide

Background B-natriuretic peptide (BNP), a neurohormone secreted from the cardiac ventricles, reflects left ventricular pressure and correlates to disease severity and prognosis. The fact that BNP levels can now be measured by a rapid assay suggests its potential usefulness in the outpatient clinic. However, if patient activity were to markedly alter BNP levels, its use would be less attractive for monitoring patients in the outpatient clinical setting. Methods A total of 30 patients (10 normal, 10 New York Heart Association [NYHA] class I-II, 10 NYHA class III-IV) exercised with an upright bicycle protocol. Exercise was carried out to 75% of maximum heart rate, and venous blood was sampled before, immediately after, and 1 hour after completion of exercise. Plasma levels of BNP, epinephrine, and norepinephrine were measured. Results BNP levels at baseline were 29 ± 11 pg/mL for normal subjects, 126 ± 26 pg/mL for NYHA I-II subjects, and 1712 ± 356 pg/mL for NYHA III-IV subjects. The change in BNP levels with exercise was significantly lower than the change in epinephrine and norepinephrine (P < .001). In normal subjects, BNP increased from 29 pg/mL to 44 pg/mL with peak exercise, still within the range of normal (<100 pg/mL) . This is compared with larger increases of norepinephrine (716 pg/mL to 1278 pg/mL) and epinephrine (52 pg/mL to 86 pg/mL) with exercise in normal subjects. There were also only small increases in BNP with exercise in patients with congestive heart failure (NYHA I-II, 30%; NYHA III-IV, 18%). For the same groups, epinephrine levels increased by 218% and 312%, respectively, and norepinephrine levels increased by 232% and 163%, respectively. One hour after completion of exercise, there were only minimal changes in BNP levels from baseline state in normal subjects (+0.9%) and patients with NYHA I-II (3.8%). In patients with NYHA III-IV, there was a 15% increase from baseline 1 hour after exercise. Conclusions BNP levels show only minor changes with vigorous exercise, making it unlikely that a normal patient would be classified as having congestive heart failure based on a BNP level obtained after activity. Prior activity should not influence BNP levels in patients with congestive heart failure. Therefore, when a patient presents to clinic with a marked change in their BNP level, it may reflect a real change in their condition. (Am Heart J 2002;143:406-11.)     

Long term exercise capacity in patients with hypertrophic cardiomyopathy treated with percutaneous transluminal septal myocardial ablation

BACKGROUND: In hypertrophic obstructive cardiomyopathy, percutaneous transluminal septal myocardial ablation (PTSMA) improves functional capacity in the short term. However, long term functional capacity is unknown. AIM: To assess the long term exercise capacity of patients with hypertrophic obstructive cardiomyopathy undergoing PTSMA. METHODS: Twenty three patients (56.5% male, mean age 44.5+/-13.6 years) who underwent PTSMA were included. All patients had also undergone a symptom limited cardiopulmonary exercise treadmill test before the procedure, then after 3 months (early follow-up) and after a mean 7.2+/-1.0 years (long term follow-up). RESULTS: Before PTSMA, mean maximal pressure gradient in the left outflow tract (LVOTGmax) was 82+/-29 mmHg, 17 patients had NYHA functional class> or = III and peak oxygen uptake (pVO2) was 18+/-4 ml/kg/min. PTSMA led to a reduction in mean LVOTGmax (to 29+/-19 mmHg, p<.0001), improvement of heart failure symptoms (NYHA> or =III in 1 patient, p<.0001) and an increase of pVO2 (to 22+/-6 ml/kg/min, p=.0002) at short term. LVOTGmax, functional class and pVO2 did not change significantly during long term follow-up compared to early follow-up. However, there was a continuous improvement in percentage predicted pVO2 over time. CONCLUSIONS: In patients with hypertrophic obstructive cardiomyopathy and symptoms of heart failure, PTSMA leads to stable long term improvement of objectively measured exercise capacity.     

A propensity-matched study of the association of physical function and outcomes in geriatric heart failure

Most heart failure (HF) patients are older adults. However, the association of functional status and outcomes in ambulatory older adults with chronic HF has not been well studied. Of the 7788 Digitalis Investigation Group (DIG) trial participants, 4036 were > or =65 years. Of these, 1369 (34%) had New York Heart Association (NYHA) class III-IV symptoms. We calculated propensity scores for NYHA III-IV symptoms for all 4036 patients using a non-parsimonious logistic regression model. We used propensity scores to match 1010 (74% of 1369) NYHA III-IV patients with 1010 of NYHA I-II patients. Kaplan-Meier and matched Cox proportion hazard analyses were used to estimate associations of NYHA class III-IV with mortality and hospitalizations. Patients had a mean age of 73 years, 31% were female, and 11% were nonwhites. All-cause mortality occurred in 394 (rate, 1385/10000 person-years) NYHA I-II and 452 (rate, 1654/10000 person-years) NYHA III-IV patients, respectively, during 2967 and 2733 years of follow up (hazard ratio: {HR}, 1.28; 95% confidence interval {CI}, 1.09-1.50; p=0.002). NYHA III-IV class was associated with increased cardiovascular (HR, 1.25; 95% CI, 1.04-1.49; p=0.016) and HF mortality (HR, 1.51; 95% CI, 1.16-1.97; p=0.002). NYHA III-IV class was not significantly associated with hospitalizations due to all causes (HR, 1.10; 95% CI, 0.96-1.25; p=0.165), cardiovascular causes (HR, 1.11; 95% CI, 0.96-1.29; p=0.150), or worsening HF (HR, 1.09, 95% CI, 0.92-1.30; p=0.330). Baseline NYHA functional class was associated with mortality but not with hospitalization in ambulatory older adults with chronic HF.     

Endogenous nitric oxide in patients with chronic heart failure (CHF): relation to functional impairment and nitrate-containing therapies

We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age 55+/-9 years) were classified according to the NYHA classes I-II (n=18, group 1) and classes III-IV (n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate-). Twenty-two healthy age-related subjects served as controls (group 3). Respiratory function, symptom-limited incremental cycloergometry and resting eNO concentration at peak (FENOp) or plateau (FENOpl) of the single-breath exhalation curve were assessed in all subjects. FENOpl was significantly lower in patients than in controls (7.8+/-2.7 and 10.6+/-2.8 ppb, respectively, P<0.005) and lower in most severe CHF patients (7.1+/-2.6 and 8.8+/-2.7 ppb in group 2 and group 1, respectively, P<0.05). A significant correlation between peak V'O(2), Watts and FENOpl (r=0.42, P<0.013 and r=0.46, P=0.008, respectively) was found. Independent of NYHA class, Nitrate+ showed higher FENOp levels than Nitrate- patients (36.9+/-15.7 vs. 28. 1+/-15.1 ppb, P<0.05). Resting eNO was lower in the most compromised CHF patients and was significantly related to exercise capacity. Nitrate-containing agents might influence the levels of eNO in these patients.     

运动负荷超声评价主动脉瓣置换术后左心室收缩功能储备

目的:应用二维超声斑点追踪技术,评价主动脉瓣置换术后运动负荷试验中的左心室收缩功能储备。方法:21例因重度主动脉瓣狭窄进行瓣膜置换术的患者(左心室射血分数>50%)行运动负荷超声心动图检查,应用二维超声斑点追踪技术测量运动负荷试验中静息状态下及峰值负荷时的左心室收缩期长轴整体应变率(GLSRs),同时记录峰值负荷时的心肌摄氧量(pVO2)。结果与21例正常健康对照者进行比较。结果:静息状态下,病例组与对照组超声指标无明显差异。峰值负荷时,病例组pVO2低于正常组(P<0.05);GLSRs及二尖瓣环心肌收缩速度(Sm)均明显低于正常组(P<0.001)且与pVO2呈正相关(GLSRs:r=0.60,P=0.0007;Sm:r=0.65,P=0.002)。多重线性回归分析,病例组峰值负荷时的左心室收缩期应变率为pVO2的唯一影响因素。结论:主动脉瓣狭窄患者瓣膜置换术后,尽管静息状态下左心室功能正常,但运动负荷试验后,左心室收缩功能储备仍然低于正常。     

Predicting peak oxygen uptake from 6-min walk test performance in male patients with left ventricular systolic dysfunction

BACKGROUND: In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one. METHODS AND RESULTS: 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2. CONCLUSIONS: Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.     

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.     

Prediction of mortality in chronic heart failure from peak oxygen consumption adjusted for either body weight or lean tissue

BACKGROUND: Peak oxygen consumption (pVO2) reflects oxygen extraction from the skeletal muscles, but is routinely corrected for body weight. We hypothesized that correcting pVO2 for lean tissue rather than total body weight would improve the prediction of prognosis in patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 272 CHF outpatients (mean age 61 +/- 12 years, New York Heart Association [NYHA] class 2.3 +/- 0.8) underwent a cardiopulmonary exercise testing and body composition assessment by dual-energy X-ray absorptiometry. During a median follow-up of 608 days (range 8-3656), 75 patients died. Univariate survival analysis showed strong survival prediction from pVO2 adjusted for total weight or lean tissue (chi2 17.7, P < .001; chi2 27.5, P < .0001, respectively). Both predicted survival significantly in bivariate analysis, (chi2 4.6, P = .032; chi2 16.6, P < .0001). The predictive effects were independent of exercise protocol (treadmill versus cycle ergometer) (both P < .001). Multivariate analysis showed that pVO2 adjusted for lean tissue had prognostic importance independently of NYHA class, ejection fraction, and ventilation and carbon dioxide production slope (P < .05 for each). In patients with NYHA class I and II (n = 160), pVO2 adjusted for lean tissue predicted outcome (P = .03). CONCLUSION: Adjustment for lean tissue instead for body weight increases the prognostic power of pVO2, particularly in patients with mild heart failure.     

Interrelationship between functional state of the right ventricle and severity of heart failure in patients with ischemic heart disease and depressed left ventricular function

Dobutamine Doppler echocardiography was carried out in 56 patients (n=56) with ischemic heart disease and depressed left ventricular function (left ventricular ejection fraction <40%) and chronic heart failure. Clinical signs of heart failure were moderate (NYHA class I-II) in 34 and severe (NYHA class III-IV) in 22 patients. Patients with moderate and severe clinical heart failure had similar degree of left ventricular myocardium impairment however those with severe symptoms had more pronounced right ventricular (RV) dysfunction (greater suppression of global and local RV contractility, greater percentage of irreversibly dysfunctional RV myocardium, lower RV contractile response to dobutamine infusion, more pronounced disturbances of RV diastolic filling). Dependence of RV pump function on pulmonary artery pressure was more evident in patients with severe clinical heart failure and marked dysfunction of RV myocardium than in patients with moderate symptoms and moderate RV myocardial dysfunction.     

Up-regulation of 'clearance' receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones

BACKGROUND: Three specific receptors for the cardiac natriuretic peptide system have been identified to date. Down-regulation of the biologically active binding sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biological and clearance (NPR-C) receptors in target tissue may explain this increase. AIM: The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF. METHODS: Eighteen patients with HF (NYHA class: I-II, n=8; III-IV, n=10) and 18 age-matched healthy subjects were studied. The affinity constant (K(d)) and density (B(max)) of binding sites were derived by saturation assays on platelet suspensions using 125I-ANP as radioligand. RESULTS: B(max) increased as a function of the severity of disease: 21.3+/-3.3 fmol/10(9) cells in class III-IV, 11.7+/-2.2 in class I-II, and 11.6+/-1.1 in controls, respectively (P=0.0179 for class III-IV vs. controls and P=0.0451 vs. NYHA I-II). CONCLUSIONS: The increase in density of 'clearance' receptors in severe HF is theoretically consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggests that clearance receptor blockade may be of potential therapeutic value in HF.     

Airway resistance in chronic heart failure measured by impulse oscillometry

BACKGROUND: Patients with chronic heart failure (CHF) complain of breathlessness and fatigue on exertion, have reduced peak oxygen consumption (pV(O(2))), and an increased ventilatory response to exercise (V(E)/V(CO(2)) slope). These limitations correlate with abnormalities of spirometry (forced expiratory volume in 1 second [FEV(1)] and forced ventilatory capacity [FVC]). Increased airway resistance by increasing the work of breathing might contribute to exercise intolerance in CHF. METHODS: Impulse oscillometry (IOS) measures airway resistance and lung compliance independently of respiratory muscle strength and patient compliance. Sound waves of varying frequencies are sent into the lungs and the amplitude and phase shift of the reflected waves give a measure of airway resistance (R) and reactance (X). Twenty-three CHF patients and 18 controls underwent peak exercise testing with metabolic gas analysis and had airway resistance assessment using the Jaeger (Würtzberg, Germany) IOS system. RESULTS: Patients had a lower pV(O(2)) (18.7 (4.0) v 39.2 (8.3) mL x kg x min; P < .0001), elevated V(E)/V(CO(2)) slope (41.6 (8.1) v 27.4 (2.9)), and lower FEV(1) (2.4 (0.4) v 3.2 (0.7) L/min; P = .0001) and FVC (3.3 (0.7) v 4.1 (1.1) L; P < .005) than controls. R and X correlated with spirometric abnormalities and were different between patients and controls (R at 5 Hz 0.44 (0.16) v 0.30 (0.15) kPa (L/s); P < .005 and X at 5 Hz -0.16 (0.08) v -0.09 (0.08) kPa (L/s); P < .05). R at 5 Hz correlated with pV(O(2)) (0.46; P = .0025) and V(E)/V(CO(2)) slope (0.43; P < .05). CONCLUSION: CHF patients have elevated airway resistance and reduced reactance measured with IOS compared with control subjects.     

Chronotropic Incompentence and Functional Capacity in Chronic Heart Failure: No Role of β‐Blockers and β‐Blocker Dose

Aim : To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO₂), focusing on the presence and dose of β‐blocker treatment. Methods : Nine hundred and sixty‐seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with β‐blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) β‐blockers daily dose group in accordance with an arbitrary cut‐off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. Results : No differences were found in NYHA or pVO2 between patients with and without β‐blockers and, similarly, between high and low β‐blocker dose groups. Twenty and sixty‐nine percent of not β‐blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on β‐blocker therapy. Patients taking β‐blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not β‐blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (β: 0.572; SE: 0.008; P < 0.0001) and NYHA class (β: ?0.499; SE: 0.001; P < 0.0001). Conclusions : ΔHR is a powerful predictor of CHF severity regardless of the presence of β‐blocker therapy and of β‐blocker daily dose.     

Ventilatory capacity and exercise tolerance in patients with chronic stable heart failure

BACKGROUND: Patients with chronic heart failure complain of breathlessness. This is associated with an increase in the ventilatory response to carbon dioxide production (VE/VCO(2) slope), yet a reduction in the maximal ventilation achieved at peak exercise. We analysed ventilatory capacity in heart failure in relation to exercise capacity. METHODS: We analysed data from 74 patients with chronic stable heart failure [age (S.D.) 50.6 (8.8) years; left ventricular ejection fraction 30 (15)%] and 36 controls [48.9 (11.5) years]. Subjects undertook maximal incremental exercise testing with metabolic gas exchange measurements to derive peak oxygen consumption (VO(2)), the VE/VCO(2) slope and ventilation. Spirometry was used to measure FEV(1) and FVC. Maximal voluntary ventilation (MVV) was calculated as FEV(1)x 35. RESULTS: Peak VO(2) was lower in patients [20.9 (7.5) ml min(-1) kg(-1) vs. 34.5 (10.1); P<0.001] and VE/VCO(2) greater [33.4 (10.7) vs. 26.0 (4.7); P<0.001]. Ventilation at peak exercise was lower in patients [63.5 (20.4) l/min vs. 86.9 (29.5); P<0.001], as was MVV [110.1 (37.9) l/min vs. 136.2 (53.1); P<0.001], but ventilation at peak as a proportion of MVV was the same in patients [60.0 (19.0)%] as controls [65.7 (12.4)%)]. There was an inverse relation between peak VO(2) and VE/VCO(2) slope (r=-0. 62; P<0.001). Percentage predicted FEV(1) correlated with ventilation at peak (r=0.62; P<0.001) and inversely with VE/VCO(2) slope (r=-0.32; P<0.001). There was no relation between percentage of MVV achieved and peak VO(2), or VE/VCO(2) slope. CONCLUSIONS: Although ventilation at peak exercise is lower in patients with heart failure than normal subjects, ventilation is the same proportion of maximal voluntary ventilation. These findings suggest that ventilatory capacity does not limit exercise capacity in heart failure.     

Short-term reproducibility of gas exchange measurements during bicycle exercise in patients with mild to moderate congestive heart failure.

A series of 45 patients with congestive heart failure due to coronary disease had semisupine bicycle exercise tests (ramp protocol, 10 W/min) on two occasions separated by 3 to 7 days in order to determine the short-term reproducibility of gas exchange measurements during symptom-limited exercise. The percentage difference (PD) between each pair of measurements (m1, m2; PD = 100%.(m2-m1): m1) were calculated. The mean PD values (+/- 1 sigma) and the single determination standard deviations (SDSD) for exercise tolerance (ET, W), peak heart rate (pHR, 1/min), peak oxygen uptake (pVO2, ml/min/kg), peak carbon dioxide output (pVCO2, ml/min/kg), and peak minute ventilation (pVE, l/min) were as follows: [table: see text] No patient reached a plateau of oxygen uptake during the last portion of the ramp exercise test. Thus, pVO2 is not an objective endpoint. The single determination standard deviations show that exercise tolerance and peak oxygen uptake do not differ as to their reproducibility. The absolute values of PD were not a function of exercise tolerance for any of the parameters studied. The PD values for ET and pVO2 were normally distributed. The data suggest that a change in ET and pVO2 must exceed 27% and 28% between two sequential studies in an individual patient in order to be significant at the 5% level, respectively. For the one-tailed test situation, the changes in ET or pVO2 must be greater than 23% in order to be significant.     

Resting lung function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure

STUDY OBJECTIVES: The aim of this study was to examine the role of resting pulmonary function and hemodynamic parameters as predictors of exercise capacity in patients with chronic heart failure. MEASUREMENTS AND RESULTS: Fifty-one patients with chronic heart failure underwent resting pulmonary function testing, including inspiratory capacity (IC) and symptom-limited, treadmill cardiopulmonary exercise testing (CPET). Right-heart catheterization and radionuclide ventriculography were performed within 2 days of CPET. Mean (+/- SD) left ventricular ejection fraction was 31 +/- 12% and cardiac index was 2.34 +/- 0.77 L/min/m(2). Percentage of predicted FEV(1) was 92 +/- 14%, percentage of predicted FVC was 94 +/- 15%, FEV(1)/FVC was 81 +/- 4%, and percentage of predicted IC was 84 +/- 18%. Mean peak oxygen uptake (peak O(2)) was 17.9 +/- 5.4 mL/kg/min. Analysis of variance among the three functional Weber classes showed statistically significant differences for pulmonary capillary wedge pressure (PCWP) and IC. Specifically, the more severe the exercise intolerance, the lower was IC and the higher was PCWP. In a multivariate stepwise regression analysis, using peak O(2) (liters per minute) as the dependent variable and the pulmonary function test measurements as independent variables, the only significant predictor selected was IC (r = 0.71, p < 0.0001). In a final stepwise regression analysis including all the independent variables of the resting pulmonary function tests and hemodynamic measurements, the two predictors selected were IC and PCWP (r(2) = 0.58). CONCLUSIONS: In patients with chronic heart failure, IC is inversely related to PCWP and is a strong independent predictor of functional capacity.     

Asthma in Patients Climbing to High and Extreme Altitudes in the Tibetan Everest Region

Objectives: The aim of this study was to investigate the behavior of asthma in patients traveling to high and extreme altitudes. Methods: Twenty-four Dutch patients with mild asthma did a trekking at high and extreme altitudes (up to 6410 m = 21030 ft) in the Tibetan Everest region. Asthma symptoms, use of asthma medication, symptoms of acute mountain sickness, spirometry, peripheral oxygen saturation, and heart rate were measured at 1300 m (baseline), and at 3875, 4310, 5175, and 6410 m. Asthma symptoms were assessed by means of a modified version of the Asthma Control Test. Symptoms of acute mountain sickness were scored by the Lake Louise self-report questionnaire. The expedition staff, consisting of seven healthy persons, acted as a control group. Results: In both asthmatics and controls, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) decreased with increasing altitude, whereas FEV1 as percent of FVC (FEV1%FVC) did not change. In both groups, peak expiratory flow (PEF) increased with increasing altitude. In general, differences in spirometric values between asthmatics and controls were not significant. Asthma symptoms did not change with increasing altitude. During ascent, less than half of the asthma patients increased their medication use. According to the Lake Louise score, no acute mountain sickness occurred, except for in the asthma group at 6410 m, which showed mild acute mountain sickness at that altitude. As expected, peripheral oxygen saturation decreased with increasing altitude in asthmatics and controls, differences between the two groups not being significant. In general, heart rate (at rest) did not change with altitude, except for an increase in asthmatics at 6410 m. Conclusions: These results suggest that traveling to high and extreme altitudes is safe for patients with mild asthma.     

Comparison of different methods of functional evaluation in patients with chronic heart failure

BACKGROUND: Stratification of the severity of heart failure has major prognostic and therapeutic implications. AIMS: To prospectively compare different methods of assessment of functional capacity in patients with chronic heart failure (CHF). METHODS AND RESULTS: We studied 143 patients (78 male and 65 female) with CHF aged less than 70 years (mean 57.3 years). Functional assessment was made clinically according to NYHA classification and according to the Goldman Activity Scale Classification (GASC). Cardiovascular performance was measured by peak O(2) consumption (pVO(2)) and anaerobic threshold (AT) at cardiopulmonary exercise test and by the distance walked during a 6-min walk test (6-MWT). Clinical scales resulted significantly related. Peak VO(2) and AT showed a mild relation with distance covered at 6-MWT (r=0.56 and r=0.46, respectively). Concordance between NYHA classification and levels of performance at cardiopulmonary exercise test or at 6-MWT was less than 50%. CONCLUSION: Our results suggest that none of the usually employed methods give a definitive assessment of functional capacity of cardiovascular system and a high degree of discordance exists among the results of different tests in the same patient. Although NYHA classification maintains its value in clinical evaluation of patients with CHF, the 6-min walk test is recommended in patients with mild-to-moderate CHF (II-III NYHA classes) as a simple and useful screening test to select patients for further diagnostic evaluation.     

Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle Diabetes Study

To determine whether diabetes is associated with reduced lung function, we studied 421 Anglo-Celt/European subjects, representing 20.5% of all patients with type 2 diabetes identified in an urban Australian catchment area of 120097 people. In addition to collection of detailed demographic and diabetes-specific data, spirometry was performed and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC) and peak expiratory flow (PEF) measured. When expressed as a percentage of those predicted (%pred) for age, sex and height, the means of all spirometric measures were reduced by > or =9.5%. After controlling for smoking, age and gender in a linear regression model, HbA(1c) was not associated with any measure of lung function (P>0.13) but diabetes duration was significantly associated with FEV1(%pred) and PEF(%pred) (P< or =0.04) and had borderline associations with FVC(%pred) and VC(%pred) (P< or =0.064). In separate analyses controlling for smoking alone, age, body mass index (BMI), coronary heart disease (CHD) and retinopathy were independently and inversely associated with FVC(%pred), FEV1(%pred) and VC(%pred) (P<0.05). In sub-group analyses, these three spirometric measures were associated with BMI, CHD and diabetes duration in males, and age and BMI in females. Pulmonary function is reduced in type 2 diabetes. Diabetes duration seems a more important influence than glycaemic control, but obesity and vascular disease may also contribute.     

Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease.

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.     

Biomechanical efficiency is impaired in patients with chronic heart failure

INTRODUCTION: Patients with chronic heart failure (CHF) have a lower peak oxygen consumption (pVO2) than normal subjects, and for a given quantity of work, have a lower total oxygen consumption (VO2) than controls. This apparent increase in biomechanical efficiency (BE) might be due to a higher proportion of anaerobic metabolism which, although leading to lower VO2 during steady state exercise, must be compensated for during recovery. METHODS: 13 patients with stable CHF and 12 controls underwent peak cycle exercise testing followed by three separate steady state exercise tests at 15%, 25% and 50% of the peak workload in random order. Oxygen consumption at steady state, deficit (during onset) and debt (during recovery) were calculated. BE was estimated as the total oxygen required to perform a given quantity of work. RESULTS: Patients had lower pVO2 and peak workload than control subjects. Absolute oxygen deficit and debt as a percentage of total oxygen consumed during the steady state tests was the same in both groups. However, once controlled for workload, VO2 deficit, debt and uptake at steady state were greater in patients than controls for the tests at 15% and 25% of peak. BE was inversely related to peak oxygen consumption in controls and patients. CONCLUSIONS: Patients with CHF have impaired BE at low work loads when compared with normal subjects.