Interest of TAPSE/sPAP ratio for noninvasive pulmonary arterial hypertension risk assessment.

BACKGROUND: Although ventriculoarterial coupling is associated with better survival in pulmonary arterial hypertension (PAH), existing PAH risk assessment method has not considered echocardiographic criteria of right ventricular to pulmonary artery coupling. We aimed to test the prognostic value of the echocardiographic tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio for noninvasive PAH risk assessment. METHODS: We retrospectively studied a cohort of 659 incident PAH patients from 4 independent French PH centers (training cohort: n = 306, validation cohort n = 353) who underwent follow-up TAPSE/sPAP measurement in addition to previously validated noninvasive risk stratification variables. The primary composite outcome was 3-year all-cause mortality or lung transplantation from re-evaluation. RESULTS: Mean age was 55 ± 17 years-old with a majority of female (66%). The three main PAH causes were connective tissue disease (26%), idiopathic (24%) and porto-pulmonary (19%). The primary composite outcome occurred in 71 (23%) patients. Multivariable Cox regression analysis retained 3 noninvasive low-risk criteria as associated with the primary composite outcome: NYHA I-II (p = 0.001), NTproBNP <300 ng/L or BNP <50 ng/L (p = 0.004), and TAPSE/sPAP >0.33 mm/mmHg (p = 0.004). The more the low-risk criteria achieved at follow-up, the better the event-free survival both in the training and validation cohort (log-rank p < 0.001). In the training cohort, the c-index for these 3 criteria, for COMPERA 2.0 and for the noninvasive French Pulmonary Hypertension Network method were 0.75, 95%CI(0.70-0.82), 0.72 95%CI(0.66-0.75), 0.71 95%CI(0.62-0.73), respectively. CONCLUSION: The 3 following dichotomized low-risk criteria: TAPSE/sPAP >0.33 mm/mmHg, NYHA I-II and NTproBNP <300 ng/L or BNP <50 ng/L allow to identify low-risk PAH patients at follow-up.

Long-term survival following initiation of home non-invasive ventilation: a European study.

INTRODUCTION: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres. METHODS: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014. RESULTS: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96). CONCLUSION: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention.

Prognostic importance of Kidney, Heart and Interstitial lung diseases (KHI triad) in PH: A machine learning study.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous, severe and progressive disease with an impact on quality of life and life-expectancy despite specific therapies. AIMS: (i) to compare prognosis significance of each PH subgroup in a cohort from a referral center, (ii) to identify phenotypically distinct high-risk PH patient using machine learning. METHODS: Patients with PH were included from 2002 to 2019 and routinely followed-up. We collected clinical, laboratory, imaging and hemodynamic variables. Four-year survival rate of each subgroups was then compared. Next, phenotypic domains were imputed with 5 eigenvectors for missing values and filtered if the Pearson correlation coefficient was>0.6. Thereafter, agglomerative hierarchical clustering was used for grouping phenotypic variables and patients: a heat map was generated and participants were separated using Penalized Model-Based Clustering. P<0.05 was considered significant. RESULTS: 328 patients were prospectively included (mean age 63±18 yo, 46% male). PH secondary to left heart disease (PH-LHD) and lung disease (PH-LD) had a significantly increased mortality compared to pulmonary arterial hypertension (PAH) patients: HR=2.43, 95%CI=(1.24-4.73) and 2.95, 95%CI=(1.43-6.07) respectively. 25 phenotypic domains were pinpointed and 3 phenogroups identified. Phenogroup 3 had a significantly increased mortality (log-rank P=0.046) compared to the others and was remarkable for predominant pulmonary disease in older male, accumulating cardiovascular risk factors, and simultaneous three major comorbidities: coronary artery disease, chronic kidney disease and interstitial lung disease. CONCLUSION: PH-LHD and PH-LD has 2-fold and 3-fold increase in mortality, respectively compared with PAH. PH patients with simultaneous kidney-cardiac-pulmonary comorbidities were identified as having high-risk of mortality. Specific targeted therapy in this phenogroup should be prospectively evaluated.

NIV Is not Adequate for High Intensity Endurance Exercise in COPD.

Noninvasive ventilation (NIV) during exercise has been suggested to sustain higher training intensity but the type of NIV interface, patient-ventilator asynchronies (PVA) or technological limitation of the ventilator may interfere with exercise. We assessed whether these parameters affect endurance exercise capacity in severe COPD patients. In total, 21 patients with severe COPD not eligible to home NIV performed three constant workload tests. The first test was carried out on spontaneous breathing (SB) and the following ones with NIV and a nasal or oronasal mask in a randomized order. PVA and indicators of ventilator performance were assessed through a comprehensive analysis of the flow pressure tracing raw data from the ventilator. The time limit was significantly reduced with both masks (406 s (197-666), 240 s (131-385) and 189 s (115-545), p < 0.01 for tests in SB, with oronasal and nasal mask, respectively). There were few PVA with an oronasal mask (median: 3.4% (1.7-5.2)) but the ventilator reached its maximal generating capacity (median flowmax: 208.0 L/s (189.5-224.8) while inspiratory pressure dropped throughout exercise (from 10.1 (9.4-11.4) to 8.8 cmH2O (8.6-10.8), p < 0.01). PVA were more frequent with nasal mask (median: 12.8% (3.2-31.6), p < 0.01). Particularly, the proportion of patients with ineffective efforts > 10% was significantly higher with nasal interface (0% versus 33.3%, p < 0.01). NIV did not effectively improve endurance capacity in COPD patients not acclimated to home NIV. This was due to a technological limitation of the ventilator for the oronasal mask and the consequence either of an insufficient pressure support or a technological limitation for the nasal mask.

The six-minute stepper test is related to muscle strength but cannot substitute for the one repetition maximum to prescribe strength training in patients with COPD.

Purpose: There are many barriers to pulmonary rehabilitation, including a limited access to evaluation centers. To cope with these difficulties, field tests are often used to prescribe endurance training. As field tests are related to muscle strength, they could also be used to prescribe strength training and increase the access to pulmonary rehabilitation in rural area. However, their validity for this purpose has never been studied. Patients and methods: The relationship between the 6-minute stepper test (6MST), 6-minute walk test, maximal workload achieved during cardiopulmonary exercise testing (Wpeak), and one repetition maximum (1RM) was assessed in 35 patients with COPD through a retrospective chart review to derive predictive equation of the 1RM from these tests. The effectiveness of these equations to prescribe strength training at 70% of the 1RM was assessed in an independent cross-validation group of 34 patients with COPD. Results: There was a moderate relationship between the 6MST, Wpeak and the 1RM (r=0.44 and r=0.41, respectively, both P≤0.01). Whatever the test, the prescription of strength training using the estimated 1RM compared with the measured 1RM resulted in a mean absolute difference and a mean bias of about 30 kg. Conclusion: The use of the 6MST and Wpeak for the prescription of strength training would result in a clinically not acceptable error. Therefore, they should not be used as a substitute for the 1RM to prescribe strength training.

People undertaking pulmonary rehabilitation are willing and able to provide accurate data via a remote pulse oximetry system: a multicentre observational study.

QUESTIONS: Can people referred to pulmonary rehabilitation easily learn to use a system for remote transmission of oximetry data? Do they consider remote transmission of oximetry data to be satisfactory? Are the transmitted data valid compared with locally stored data? DESIGN: Multicentre, prospective, observational study. PARTICIPANTS: One hundred and five adults with chronic respiratory disease who were referred to pulmonary rehabilitation. INTERVENTION: At an initial session, participants were taught to record and transmit their oximetry data to a remote server. At subsequent testing session(s), participants were requested to independently activate and use the oximetry monitoring system for a period of exercise on a cycle ergometer, until autonomy with the system was demonstrated. A subgroup of five participants undertook five 45-minute training sessions to generate a dataset to assess whether the transmitted data were valid compared with the locally stored data. OUTCOME MEASURES: Outcome measures included the number of sessions needed to become autonomous, participant satisfaction with the system, and measures of the validity of the transmitted data. RESULTS: Participants became autonomous quickly: 86% at the first testing session and 100% within three testing sessions. At least 98% of participants agreed that the system was easy to use and they would be willing to use it throughout pulmonary rehabilitation. The system transmitted usable data from 98% (95% CI 96 to 100) of sessions and introduced minimal artefact. Mean absolute differences were 0.365 beats/minute for heart rate and 0.133% for oxyhaemoglobin saturation. For heart rate, exact agreement was 72% (SD 9) and similar agreement (within 3 beats/minute) was 99% (SD 1). For oxyhaemoglobin saturation, exact agreement was 87% (SD 3) and similar agreement (within 3%) was 100% (SD 0). CONCLUSION: The telemonitoring system used in this study was sufficiently valid and acceptable for use in at-home pulmonary rehabilitation by people with chronic respiratory disease. STUDY REGISTRATION: ClinicalTrials.gov NCT03295474 and NCT03004716 (subgroup study).

Home-based Neuromuscular Electrical Stimulation as an Add-on to Pulmonary Rehabilitation Does Not Provide Further Benefits in Patients With Chronic Obstructive Pulmonary Disease: A Multicenter Randomized Trial.

OBJECTIVE: To assess the additional effect of a home-based neuromuscular electrical stimulation (NMES) program as an add-on to pulmonary rehabilitation (PR), on functional capacity in subjects with chronic obstructive pulmonary disease (COPD). DESIGN: Single-blind, multicenter randomized trial. SETTING: Three PR centers. PARTICIPANTS: Subjects with severe to very severe COPD (N=73; median forced expiratory volume in 1 second, 1L (25th-75th percentile, 0.8-1.4L) referred for PR. Twenty-two subjects discontinued the study, but only 1 dropout was related to the intervention (leg discomfort). INTERVENTION: Subjects were randomly assigned to either PR plus quadricipital home-based NMES (35Hz, 30min, 5 time per week) or PR without NMES for 8 weeks. MAIN OUTCOME MEASURE: The 6-minute walk test (6MWT) was used to assess functional capacity. RESULTS: Eighty-two percent of the scheduled NMES sessions were performed. In the whole sample, there were significant increases in the distance walked during the 6MWT (P<.01), peak oxygen consumption (P=.02), maximal workload (P<.01), modified Medical Research Council dyspnea scale (P<.01), and Saint George's Respiratory Questionnaire total score (P=.01). There was no significant difference in the magnitude of change for any outcome between groups. CONCLUSIONS: Home-based NMES as an add-on to PR did not result in further improvements in subjects with severe to very severe COPD; moreover, it may have been a burden for some patients.

Exercise testing in patients with diaphragm paresis.

PURPOSE: Diaphragm paresis (DP) is characterized by abnormalities of respiratory muscle function. However, the impact of DP on exercise capacity is not well known. This study was performed to assess exercise tolerance in patients with DP and to determine whether inspiratory muscle function was related to exercise capacity, ventilatory pattern and cardiovascular function during exercise. METHODS: This retrospective study included patients with DP who underwent both diaphragmatic force measurements, and cardiopulmonary exercise testing (CPET). RESULTS: Fourteen patients were included. Dyspnea was the main symptom limiting exertion (86%). Exercise capacity was slightly reduced (median VO2peak: 80% [74.5%-90.5%]), mostly due to ventilatory limitation. Diaphragm and overall inspiratory muscle function were correlated with exercise ventilation. Moreover, overall inspiratory muscle function was related with oxygen consumption (r=0.61) and maximal workload (r=0.68). CONCLUSIONS: DP decreases aerobic capacity due to ventilatory limitation. Diaphragm function is correlated with exercise ventilation whereas overall inspiratory muscle function is correlated with both exercise capacity and ventilation suggesting the importance of the accessory inspiratory muscles during exercise for patients with DP. Further larger prospective studies are needed to confirm these results.

Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension.

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L·min-1·m-2) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.

Six-minute Stepper Test to Set Pulmonary Rehabilitation Intensity in Patients with COPD - A Retrospective Study.

Pulmonary rehabilitation (PR) improves outcomes in patients with chronic obstructive pulmonary disease (COPD). Optimal assessment includes cardiopulmonary exercise testing (CPET), but consultations are limited. Field tests could be used to individualize PR instead of CPET. The six-minute stepper test (6MST) is easy to set up and its sensitivity and reproducibility have previously been reported in patients with COPD. The aim of this study was to develop a prediction equation to set intensity in patients attending PR, based on the 6MST. The following relationships were analyzed: mean heart rate (HR) during the first (HR1-3) and last (HR4-6) 3 minutes of the 6MST and HR at the ventilatory threshold (HRvt) from CPET; step count at the end of the 6MST and workload at the Ventilatory threshold (VT) (Wvt); and forced expiratory volume in 1 second and step count during the 6MST. This retrospective study included patients with COPD referred for PR who underwent CPET, pulmonary function evaluations and the 6MST. Twenty-four patients were included. Prediction equations were HRvt = 0.7887 × HR1-3 + 20.83 and HRvt = 0.6180 × HR4-6 + 30.77. There was a strong correlation between HR1-3 and HR4-6 and HRvt (r = 0.69, p < 0.001 and r = 0.57, p < 0.01 respectively). A significant correlation was also found between step count and LogWvt (r = 0.63, p < 0.01). The prediction equation was LogWvt = 0.001722 × step count + 1.248. The 6MST could be used to individualize aerobic training in patients with COPD. Further prospective studies are needed to confirm these results.

Altered synchrony of right ventricular contraction in borderline pulmonary hypertension.

Imaging studies have shown that pulmonary hypertension (PH) is associated with inhomogenous right ventricular (RV) regional contraction, or dyssynchrony, and that this is of prognostic relevance. This study aimed at the identification and functional significance of RV dyssynchrony in borderline PH defined by a mean pulmonary artery pressure between (mPAP) 20 and 25 mmHg. RV dyssynchrony was measured by 2-dimensional speckle tracking echocardiography in 17 patients with pulmonary arterial hypertension (PAH), 13 patients with borderline PH and 14 controls. Dyssynchrony was defined as the R-R interval-corrected standard deviation of the times to peak-systolic strain for the basal and medium segments of the RV. All the PH patients underwent a right heart catheterization. RV dyssynchrony amounted to 69 ± 34 ms in PAH, 47 ± 23 ms in borderline PH and 8 ± 6 ms in controls, all different from each other (p < 0.05). RV dyssynchrony in borderline PH was the only parameter of RV systolic dysfunction in 11 of 13 (85%) of the patients. RV dyssynchrony was accompanied by postsystolic shortening and correlated to RV fractional area change, not to mPAP or pulmonary vascular resistance. RV dyssynchrony occurs in borderline PH and may reflect early RV-arterial uncoupling.

A Randomized Controlled Trial on the Effect of Needle Gauge on the Pain and Anxiety Experienced during Radial Arterial Puncture.

BACKGROUND: Arterial punctures for assessment of arterial blood-gases can be a painful procedure. Lidocaine can be used to reduce pain prior to needle insertion but it is not a widely accepted practice. The purpose of this study was to determine whether a large size needle induces more pain compared to a smaller size needle for radial arterial puncture and to assess the anxiety associated with radial arterial punctures. METHODS: We conducted a prospective, double-blind, randomized, controlled, monocentric study including all outpatients who had a planned assessment of arterial blood gas analysis. Patients were randomized to have the arterial puncture performed with a 23 or a 25 G needle. The main judgement criteria was pain during arterial puncture. Visual analogue scale for pain (VAS-P) and visual analogue scale for anxiety (VAS-A) were used to assess pain and anxiety during radial arterial puncture. RESULTS: Two hundred consecutive patients were randomized. The 25 G needle was as painful as the 23 G needle (6.63 mm [0-19 mm] vs. 5.21 mm [0-18.49 mm], respectively, p = 0.527). Time for arterial puncture was longer with the 25 G needle than with the 23 G needle (42 s [35-55 s] vs. 33 s [24.5-35 s], respectively, p = 0.002). There was a correlation between the level of anxiety prior to the arterial puncture and the pain experienced by the patients (p: 0.369, p<0.0001). There was a correlation between the pain experienced by patients and the anxiety experienced in anticipation of another arterial puncture (p: 0.5124, p<0.0001). CONCLUSIONS: The use of 23 G needle allows quicker arterial sampling and is not associated with increased pain and symptoms. Anxiety was correlated with the pain experienced by patients during arterial punctures. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02320916.

Cephalic versus oronasal mask for noninvasive ventilation in acute hypercapnic respiratory failure.

OBJECTIVE: Compared to oronasal interfaces, a cephalic mask has a larger inner volume, covers the entire anterior surface of the face and limits the risk of deleterious cutaneous side effects during noninvasive ventilation (NIV). The present clinical study aimed to compare the clinical efficacy of a cephalic mask versus an oronasal mask in patients with acute hypercapnic respiratory failure (AHRF). DESIGN AND SETTING: Randomized controlled study in a Respiratory Intermediate Care Unit. PATIENTS: All consecutive patients admitted for AHRF were randomly assigned to receive bilevel NIV either with a cephalic mask (n = 17) or an oronasal mask (n = 17) during the first 48 h. MEASUREMENTS: The main outcome criterion was the improvement of arterial pH, 24 h after NIV initiation. Secondary criteria included PaCO(2) and physiological parameters. RESULTS: Compared to values at inclusion, pH, PaCO(2), encephalopathy score, respiratory distress score and respiratory frequency improved significantly and similarly with both masks. None of these parameters showed statistically significant differences between the masks at each time point throughout the study period. Mean delivered inspiratory and expiratory pressures were similar in both patient groups. Tolerance of the oronasal mask was improved at 24 h and further. One patient with the cephalic mask suffered from claustrophobia that did not lead to premature study interruption. CONCLUSIONS: In spite of its larger inner volume, the cephalic mask has the same clinical efficacy and requires the same ventilatory settings as the oronasal mask during AHRF.