Gaël Deboeck

Exercise testing in pulmonary arterial hypertension and in chronic heart failure

Exercise capacity is reduced in pulmonary arterial hypertension and in chronic left heart failure, but it is not known whether the cardiopulmonary exercise testing profile is different in the two conditions at the same severity of functional limitation. Nineteen patients with pulmonary arterial hypertension and 19 with chronic heart failure underwent a 6‐min walk test and symptom-limited maximal incremental cycle ergometry. The patients with pulmonary arterial hypertension and chronic heart failure did not differ in New York Heart Association Functional Class (mean±sem 2.8±0.1 versus 2.8±0.2), 6‐min walking distance (395±30 versus 419±20 m), peak work-rate, oxygen consumption, ventilation and cardiac frequency. However, patients with pulmonary arterial hypertension exhibited higher dyspnoea scores (5.8±0.6 versus 3.8±0.5) higher ventilatory equivalents for carbon dioxide (58±3 versus 44±3 at the anaerobic threshold) and lower peak oxygen pulse (5.9±0.4 versus 8.7±0.5 mL·beat−1, or 53±4 versus 64±4% of the predicted value). It is concluded that the cardiopulmonary exercise testing profile in pulmonary arterial hypertension differs from that in chronic heart failure by showing more dyspnoea at comparable work-rates, related to greater reductions in ventilatory efficiency and stroke volume.

Physiological response to the six-minute walk test in pulmonary arterial hypertension

The 6-min walk test (6MWT) is commonly used to evaluate exercise capacity in patients with pulmonary arterial hypertension (PAH). However, little is known about the corresponding metabolic stress as measured by cardiopulmonary exercise testing. The present study, therefore, measured ventilatory variables and heart rate during the 6MWT and symptom-limited incremental maximal exercise testing in 20 patients with PAH. The distance walked in 6 min was 450±22 m (mean±se). During the 6MWT, ventilation, O2 consumption, CO2 production and heart rate increased during the first 3–4 min, and then remained stable. As compared with the maximum values measured during the cardiopulmonary exercise test, O2 consumption tended to be higher (14.2±0.6 versus 12.9±0.7 mL·kg−1·min−1), while maximum ventilation (46±3 versus 57±4 L·min−1), respiratory quotient (0.90±0.02 versus 1.15±0.02) and heart rate (119±4 versus 135±4 beats·min−1) remained lower. In conclusion, patients with pulmonary arterial hypertension exercise at higher aerobic capacity and lower metabolic stress during the 6MWT than during a cardiopulmonary exercise test.

Effect of systemic inflammation on inspiratory and limb muscle strength and bulk in cystic fibrosis

RATIONALE Diaphragm thickness is increased in cystic fibrosis (CF), but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation. OBJECTIVES To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with CF. METHODS In 38 stable patients with CF and 20 matched control subjects, we measured fat-free mass (FFM), inspiratory muscle strength, diaphragm thickness, quadriceps and biceps strength and cross-sectional area, and circulating levels of leukocytes, C-reactive protein, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, tumor necrosis factor-alpha soluble receptors, and immunoglobulin G. MEASUREMENTS AND MAIN RESULTS Patients had increases in several inflammatory markers that correlated with the severity of lung disease and nutritional depletion. Compared with control subjects, patients with CF had increased diaphragm thickness and inspiratory muscle strength and showed a trend toward a reduction in limb muscle strength and bulk. Multiple regression analyses identified FFM and airway resistance as independent predictors of diaphragm thickness, but systemic inflammation had no (or only a minor) predictive effect on FFM, inspiratory muscle strength, diaphragm thickness, and limb muscle strength and bulk. CONCLUSIONS In patients with CF, the intensity of systemic inflammation does not account significantly for the variance of FFM and diaphragm or limb muscle strength and bulk. Training of the diaphragm in CF occurs despite the presence of systemic inflammation.

Beta-adrenergic blockade and metabo-chemoreflex contributions to exercise capacity.

PURPOSE Exercise-induced dyspnea in patients with cardiopulmonary diseases may be related to sympathetic nervous system activation, with increased metabo- and/or chemosensitivities. Whether this mechanism plays a role in exercising normal subjects remains unclear. METHODS Muscle sympathetic nerve activity (MSNA), HR, ventilation (V(E)), O2 saturation (SpO2), and end-tidal PCO2 (PetCO2) were measured in 14 healthy young adults after 1 wk of beta1-receptor blockade with bisoprolol 5 mg x d(-1) versus placebo after a double-blind, placebo-controlled, randomized crossover design. The MSNA and the ventilatory responses to hyperoxic hypercapnia (7% CO2 in O2), DeltaV(E)/DeltaPetCO2, and isocapnic hypoxia (10% O2 in N2), DeltaV(E)/DeltaSpO2, and to an isometric muscle contraction followed by a local circulatory arrest (metaboreflex) were determined at rest followed by an incremental cardiopulmonary exercise test. RESULTS Bisoprolol did not change the V(E) and MSNA responses to hypercapnia, hyperoxia, or isometric muscle contraction or ischemia. Bisoprolol decreased maximum O2 uptake (P < 0.05), workload (P < 0.05), and HR (P < 0.0001) and both V(E)/VO2 and V(E)/VCO2 slopes (P < 0.05). CONCLUSIONS These results suggest that decreased aerobic exercise capacity after intake of beta-blockers is accompanied by decreased ventilation at any metabolic rate. However, this occurs without detectable change in the sympathetic nervous system tone or in metabo- or chemosensitivity and is therefore probably of hemodynamic origin.

Pulmonary hypertension and ventilation during exercise: Role of the pre-capillary component

BACKGROUND Excessive exercise-induced hyperventilation and high prevalence of exercise oscillatory breathing (EOB) are present in patients with post-capillary pulmonary hypertension (PH) complicating left heart disease (LHD). Patients with pre-capillary PH have even higher hyperventilation but no EOB. We sought to determine the impact of a pre-capillary component of PH on ventilatory response to exercise in patients with PH and left heart disease. METHODS We retrospectively compared patients with idiopathic or heritable pulmonary arterial hypertension (PAH, n = 29), isolated post-capillary PH (IpcPH, n = 29), and combined post- and pre-capillary PH (CpcPH, n = 12). Diastolic pressure gradient (DPG = diastolic pulmonary artery pressure - pulmonary wedge pressure) was used to distinguish IpcPH (DPG <7 mm Hg) from CpcPH (DPG ≥7 mm Hg). RESULTS Pulmonary vascular resistance (PVR) was higher in PAH, intermediate in CpcPH, and low in IpcPH. All patients with CpcPH but 1 had PVR >3 Wood unit. Exercise-induced hyperventilation (high minute ventilation over carbon dioxide production, low end-tidal carbon dioxide) was marked in PAH, intermediate in CpcPH, and low in IpcPH (p < 0.001) and correlated with DPG and PVR. Prevalence of EOB decreased from IpcPH to CpcPH to PAH (p < 0.001). CONCLUSIONS Patients with CpcPH may have worse hemodynamics than patients with IpcPH and distinct alterations of ventilatory control, consistent with more exercise-induced hyperventilation and less EOB. This might be explained at least in part by the presence and extent of pulmonary vascular disease.

Physiological response to the 6-minute walk test in chronic heart failure patients versus healthy control subjects.

Background The distance walked in 6 minutes (6MWD) has been reported to be linearly related to peak oxygen uptake (VO2) in cardiac diseases and in lung diseases. In these patients, the VO2 during a 6-min walk test (walkVO2) has been found to be nearly equivalent to peakVO2, but with a lower respiratory exchange ratio (RER). Whether these observations translate to the less functionally impaired patients or healthy control subjects is not exactly known. Methods Thirty-two healthy control subjects and 15 chronic heart failure (CHF) patients performed a 6-min walk test and a maximal cardiopulmonary exercise test (CPET) both with measurements of gas exchange. Results The 6MWD and peakVO2 were linearly correlated, but with an increased slope appearing above 532 m. In CHF patients, walkVO2 was similar to peakVO2, but with lower heart rate and ventilation than measured at peak exercise. In healthy control subjects, VO2, ventilation and heart rate were lower during the 6-min walk than at maximal exercise but higher than at the anaerobic threshold. The RER during the 6-min walk remained <1 in both groups. Conclusions Above 500 m, 6MWD becomes less sensitive to any increase in peakVO2. Furthermore, CHF patients and healthy control subjects exercise respectively at maximal and high VO2, but below the anaerobic threshold (as assessed by a CPET) during the 6-min walk test.

Maximal cardiac output determines 6 minutes walking distance in pulmonary hypertension

Purpose The 6 minutes walk test (6MWT) is often shown to be the best predictor of mortality in pulmonary hypertension (PH) probably because it challenges the failing heart to deliver adequate cardiac output. We hypothesised that the 6MWT elicits maximal cardiac output as measured during a maximal cardiopulmonary exercise testing (CPET). Methods 18 patients with chronic thromboembolic pulmonary hypertension (n = 12) or pulmonary arterial hypertension (n = 6) and 10 healthy subjects performed a 6MWT and CPET with measurements of cardiac output (non invasive rebreathing device) before and directly after exercise. Heart rate was measured during 6MWT with a cardiofrequence meter. Results Cardiac output and heart rate measured at the end of the 6MWT were linearly related to 6MW distance (mean±SD: 490±87 m). Patients with a high NT-pro-BNP achieve a maximum cardiac output during the 6MWT, while in normal subjects and in patients with a low-normal NT-proBNP, cardiac output at the end of a 6MWT was lower than achieved at maximum exercise during a CPET. In both cases, heart rate is the major determinant of exercise-induced increase in cardiac output. However, stroke volume increased during CPET in healthy subjects, not in PH patients. Conclusion Maximal cardiac output is elicited by 6MWT in PH patients with failing right ventricle. Cardiac output increase is dependent on chronotropic response in patients with PH.

Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.

Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l(-1)·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max (P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women.

Decreased ventilatory response to exercise by dopamine-induced inhibition of peripheral chemosensitivity.

The contribution of the peripheral chemoreflex to the ventilatory response to exercise and aerobic exercise capacity remains incompletely understood. Low-dose dopamine has been reported to specifically inhibit the peripheral chemoreceptors. We therefore investigated the effects of intravenous dopamine (3 microg kg(-1)min(-1)) on cardiopulmonary exercise test (CPET) variables in 13 healthy young male subjects. The study was prospective, placebo-controlled, and randomized with more than 24h between placebo and dopamine administrations. During the CPET, dopamine decreased the .V(E)/.V(CO2) output slope (24.61+/-1.84 vs. 23.09+/-1.81, placebo vs. Dopamine respectively, p=0.025), without affecting maximum workload, .V(E) and O(2) uptake. In conclusion, our study reveals that inhibition of peripheral chemoreflex function with dopamine decreases the .V(E)/.V(CO2) slope during dynamic exercise, with no change in aerobic exercise capacity.

Pulmonary vascular function and aerobic exercise capacity at moderate altitude

Purpose There has been suggestion that a greater “pulmonary vascular reserve” defined by a low pulmonary vascular resistance (PVR) and a high lung diffusing capacity (DL) allow for a superior aerobic exercise capacity. How pulmonary vascular reserve might affect exercise capacity at moderate altitude is not known. Methods Thirty-eight healthy subjects underwent an exercise stress echocardiography of the pulmonary circulation, combined with measurements of DL for nitric oxide (NO) and carbon monoxide (CO) and a cardiopulmonary exercise test at sea level and at an altitude of 2250 m. Results At rest, moderate altitude decreased arterial oxygen content (CaO2) from 19.1 ± 1.6 to 18.4 ± 1.7 mL·dL−1, P < 0.001, and slightly increased PVR, DLNO, and DLCO. Exercise at moderate altitude was associated with decreases in maximum O2 uptake (V˙O2max), from 51 ± 9 to 43 ± 8 mL·kg−1⋅min−1, P < 0.001, and CaO2 to 16.5 ± 1.7 mL·dL−1, P < 0.001, but no different cardiac output, PVR, and pulmonary vascular distensibility. DLNO was inversely correlated to the ventilatory equivalent of CO2 (V˙E/V˙CO2) at sea level and at moderate altitude. Independent determinants of V˙O2max as determined by a multivariable analysis were the slope of mean pulmonary artery pressure–cardiac output relationship, resting stroke volume, and resting DLNO at sea level as well as at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude was independently predicted by more pronounced exercise-induced decrease in CaO2 at moderate altitude. Conclusion Aerobic exercise capacity is similarly modulated by pulmonary vascular reserve at moderate altitude and at sea level. Decreased aerobic exercise capacity at moderate altitude is mainly explained by exercise-induced decrease in arterial oxygenation.