mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Pulmonary hypertension during exercise underlies unexplained exertional dyspnoea in patients with Type 2 diabetes.

AIMS: To compare the cardiac function and pulmonary vascular function during exercise between dyspnoeic and non-dyspnoeic patients with Type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Forty-seven T2DM patients with unexplained dyspnoea and 50 asymptomatic T2DM patients underwent exercise echocardiography combined with ergospirometry. Left ventricular (LV) function [stroke volume, cardiac output (CO), LV ejection fraction, systolic annular velocity (s')], estimated LV filling pressures (E/e'), mean pulmonary arterial pressures (mPAPs) and mPAP/COslope were assessed at rest, low- and high-intensity exercise with colloid contrast. Groups had similar patient characteristics, glycemic control, stroke volume, CO, LV ejection fraction, and E/e' (P > 0.05). The dyspnoeic group had significantly lower systolic LV reserve at peak exercise (s') (P = 0.021) with a significant interaction effect (P < 0.001). The dyspnoeic group also had significantly higher mPAP and mPAP/CO at rest and exercise (P < 0.001) with significant interaction for mPAP (P < 0.009) and insignificant for mPAP/CO (P = 0.385). There was no significant difference in mPAP/COslope between groups (P = 0.706). However, about 61% of dyspnoeic vs. 30% of non-dyspnoeic group had mPAP/COslope > 3 (P = 0.009). The mPAP/COslope negatively predicted V̇O2peak in dyspneic group (ß = -1.86, 95% CI: -2.75, -0.98; multivariate model R2:0.54). CONCLUSION: Pulmonary hypertension and less LV systolic reserve detected by exercise echocardiography with colloid contrast underlie unexplained exertional dyspnoea and reduced exercise capacity in T2DM.

Effects of inspiratory muscle training on exertional breathlessness in patients with unilateral diaphragm dysfunction: a randomised trial.

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD. Methods: 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure (PI,max), n=10) or sham training (10% PI,max, n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal (Pes) and gastric (Pga) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise. Results: The IMT group (from 45±6 to 62±23% PI,max) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. PI,max, TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH2O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, Pes, Pga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05). Conclusion: The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles.

Measurement validity of an electronic training device to assess breathing characteristics during inspiratory muscle training in patients with weaning difficulties.

Inspiratory muscle training (IMT) improves respiratory muscle function and might enhance weaning outcomes in patients with weaning difficulties. An electronic inspiratory loading device provides valid, automatically processed information on breathing characteristics during IMT sessions. Adherence to and quality of IMT, as reflected by work of breathing and power generated by inspiratory muscles, are related to improvements in inspiratory muscle function in patients with chronic obstructive pulmonary disease. The aim of this study was to investigate the validity of an electronic training device to assess and provide real-time feedback on breathing characteristics during inspiratory muscle training (IMT) in patient with weaning difficulties. Patients with weaning difficulties performed daily IMT sessions against a tapered flow-resistive load of approximately 30 to 50% of the patient's maximal inspiratory pressure. Airflow and airway pressure measurements were simultaneously collected with the training device (POWERbreatheKH2, POWERbreathe International Ltd, UK) and a portable spirometer (reference device, Pocket-Spiro USB/BT100, M.E.C, Belgium). Breath by breath analysis of 1002 breaths of 27 training sessions (n = 13) against a mean load of 46±16% of the patient's maximal inspiratory pressure were performed. Good to excellent agreement (Intraclass correlation coefficients: 0.73-0.97) was observed for all breathing characteristics. When individual differences were plotted against mean values of breaths recorded by both devices, small average biases were observed for all breathing characteristics. To conclude, the training device provides valid assessments of breathing characteristics to quantify inspiratory muscle effort (e.g. work of breathing and peak power) during IMT in patients with weaning difficulties. Availability of valid real-time data of breathing responses provided to both the physical therapist and the patient, can be clinically usefull to optimize the training stimulus. By adapting the external load based on the visual feedback of the training device, respiratory muscle work and power generation during IMT can be maximized during the training.

High-intensity exercise impairs extradiaphragmatic respiratory muscle perfusion in patients with COPD.

The study investigated whether high-intensity exercise impairs inspiratory and expiratory muscle perfusion in patients with chronic obstructive pulmonary disease (COPD). We compared respiratory local muscle perfusion between constant-load cycling[sustained at 80% peak work rate (WRpeak)] and voluntary normocapnic hyperpnea reproducing similar work of breathing (WoB) in 18 patients [forced expiratory volume in the first second (FEV1): 58 ± 24% predicted]. Local muscle blood flow index (BFI), using indocyanine green dye, and fractional oxygen saturation (%StiO2) were simultaneously assessed by near-infrared spectroscopy (NIRS) over the intercostal, scalene, rectus abdominis, and vastus lateralis muscles. Cardiac output (impedance cardiography), WoB (esophageal/gastric balloon catheter), and diaphragmatic and extradiaphragmatic respiratory muscle electromyographic activity (EMG) were also assessed throughout cycling and hyperpnea. Minute ventilation, breathing pattern, WoB, and respiratory muscle EMG were comparable between cycling and hyperpnea. During cycling, cardiac output and vastus lateralis BFI were significantly greater compared with hyperpnea [by +4.2 (2.6-5.9) L/min and +4.9 (2.2-7.8) nmol/s, respectively] (P < 0.01). Muscle BFI and %StiO2 were, respectively, lower during cycling compared with hyperpnea in scalene [by -3.8 (-6.4 to -1.2) nmol/s and -6.6 (-8.2 to -5.1)%], intercostal [by -1.4 (-2.4 to -0.4) nmol/s and -6.0 (-8.6 to -3.3)%], and abdominal muscles [by -1.9 (-2.9 to -0.8) nmol/s and -6.3 (-9.1 to -3.4)%] (P < 0.001). The difference in respiratory (scalene and intercostal) muscle BFI between cycling and hyperpnea was associated with greater dyspnea (Borg CR10) scores (r = -0.54 and r = -0.49, respectively, P < 0.05). These results suggest that in patients with COPD, 1) locomotor muscle work during high-intensity exercise impairs extradiaphragmatic respiratory muscle perfusion and 2) insufficient adjustment in extradiaphragmatic respiratory muscle perfusion during high-intensity exercise may partly explain the increased sensations of dyspnea.NEW & NOTEWORTHY We simultaneously assessed the blood flow index (BFI) in three respiratory muscles during hyperpnea and high-intensity constant-load cycling sustained at comparable levels of work of breathing and respiratory neural drive in patients with COPD. We demonstrated that high-intensity exercise impairs respiratory muscle perfusion, as intercostal, scalene, and abdominal BFI increased during hyperpnea but not during cycling. Insufficient adjustment in respiratory muscle perfusion during exercise was associated with greater dyspnea sensations in patients with COPD.