Impact of cystic fibrosis multidisciplinary virtual clinics on patient experience, time commitments and costs.

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior. METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

Preoperative cardiopulmonary exercise testing improves risk assessment of morbidity and length of stay following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the standard treatment for selected patients with peritoneal malignancy. The optimal means of assessing risk prior to these complex operations is not known. This study explored the associations between preoperative cardiopulmonary exercise testing (CPET) variables and postoperative outcomes following elective CRS and HIPEC. This study included patients who underwent routine preoperative CPET prior to elective CRS and HIPEC at Royal Prince Alfred Hospital in Sydney between July 2017 and July 2020. CPET was performed using a cycle ergometer and measured peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). Outcomes included in-hospital morbidity, length of intensive care unit (ICU) stay and hospital stay. The associations between preoperative CPET variables and postoperative morbidity were assessed using univariate and multivariate analyses. A total of 129 patients were included. Mean age was 56 years (standard deviation (SD) 12.5 years), and colorectal cancer was the most common indication for CRS and HIPEC. The overall complication rate was 69%, and two (1.6%) patients died in hospital. Patients who did not develop any postoperative complication had slightly higher preoperative AT and VO2 peak and shorter length of hospital stay. Data in this study support the role of CPET prior to CRS and HIPEC as an adjunct to improve risk assessment.

Myocardial fibrosis in Type 2 Diabetes is associated with functional and metabolomic parameters.

AIMS: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. METHODS: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. RESULTS: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). CONCLUSIONS: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.

Quality of home spirometry performance amongst adults with cystic fibrosis.

Spirometry is usually performed under the supervision of a trained respiratory scientist to ensure acceptability and repeatability of results. To evaluate the quality of spirometry performance by adult cystic fibrosis (CF) patients with and without observation by a trained respiratory scientist, an observational, single centre study was conducted between February to December 2020. 74 adults were recruited and instructed to perform spirometry without supervision within 24 h of their remote CF clinic consultation. Spirometry was repeated at their consultation, supervised by a respiratory scientist using video conferencing. The majority of patients achieved grade A (excellent) or B (very good) spirometry quality with (95%) and without supervision (93%) independent of lung function severity. Similarly, forced expiratory volume in 1 second demonstrated no significant differences with paired spirometry performed within a 24 hour period. For a large proportion of adult CF patients, unsupervised portable spirometry produces acceptable and repeatable results.

Feasibility and acceptability of a preoperative exercise program for patients undergoing major cancer surgery: results from a pilot randomized controlled trial.

OBJECTIVE: To establish the feasibility and acceptability of a preoperative exercise program, and to obtain pilot data on the likely difference in key surgical outcomes to inform the sample size calculation for a full-scale trial. DESIGN: Pilot randomized controlled trial. SETTING: Royal Prince Alfred Hospital, Sydney, Australia. SUBJECTS: We included patients undergoing elective pelvic exenteration or cytoreductive surgery aged 18 to 80 years, who presented to the participating gastrointestinal surgeon at least 2 weeks prior to surgery. Patients presenting cognitive impairment, co-morbidity preventing participation in exercise, inadequate English language, currently participating in an exercise program or unable to attend the exercise program sessions were excluded. METHODS: Participants were randomized to a 2-6 weeks preoperative, face-to-face, individualised exercise program or to usual care. Feasibility was assessed with consent rates to the study, and for the intervention group, retention and adherence rates to the preoperative exercise program. Acceptability of the exercise program was assessed with a semi-structured questionnaire exploring the advice received and the amount, duration and intensity of the exercise program. In addition, postoperative complication rates (Clavien-Dindo), length of hospital stay and self-reported measures of health-related quality of life (SF-36v2) were collected at baseline, day before surgery and in-hospital up to discharge from hospital. RESULTS: Of 122 patients screened, 26 (21%) were eligible and 22 (85%) accepted to participate in the trial and were randomized to the intervention (11; 50%) or control group (11; 50%). The median age of the include participants was 63 years. Adherence to the preoperative exercise sessions was 92.7%, with all participants either satisfied (33%) or extremely satisfied (67%) with the overall design of the preoperative exercise program. No significant differences in outcomes were found between groups. CONCLUSIONS: The results of our pilot trial demonstrate that a preoperative exercise program is feasible and acceptable to patients undergoing major abdominal cancer surgery. There is an urgent need for a definite trial investigating the effectiveness of a preoperative exercise program on postoperative outcomes in patients undergoing major abdominal cancer surgery. This could potentially reduce postoperative complication rates, length of hospital stay and subsequently overall health care costs. TRIAL REGISTRATION: ACTRN12617001129370. Registered on August 1, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373396&showOriginal=true&isReview=true.

Inspiratory Muscle Training Improves Inspiratory Muscle Strength and Functional Exercise Capacity in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Randomised Controlled Study.

BACKGROUND: Exercise intolerance is present even in the early stages of pulmonary arterial hypertension (PAH) and is associated with poorer prognosis. Respiratory muscle dysfunction is common and may contribute to exercise limitation. We sought to investigate the effects of inspiratory muscle training (IMT) to improve exercise capacity in PAH. METHODS: Adults with PAH were prospectively recruited and randomly assigned to either IMT or a control group. At baseline and after 8 weeks, assessment of respiratory muscle function, pulmonary function, neurohormonal activation, 6-minute walk distance and cardiopulmonary exercise testing variables were conducted. Inspiratory muscle strength was assessed by maximal static inspiratory pressure (PImax). The IMT group performed two cycles of 30 breaths at 30-40% of their PImax 5 days a week for 8 weeks. RESULTS: Twelve (12) PAH patients (60±14 years, 10 females) were recruited and randomised (six in the IMT group and six in the control group). After 8 weeks, the IMT group improved PImax by 31 cmH2O compared with 10 cmH2O in controls, p=0.02. Following IMT, 6-minute walk distance improved by 24.5 m in the IMT group and declined by 12 m in the controls (mean difference 36.5 m, 95% CI 3.5-69.5, p=0.03). There was no difference in peak oxygen uptake between-groups (mean difference 0.4 mL/kg/min, 95% CI -2.6 to 3.4, p=0.77). There was no difference in the mean change between-groups in neurohormonal activation or pulmonary function. CONCLUSION: In this pilot randomised controlled study, IMT improved PImax and 6-minute walk distance in PAH patients.

Multimodality Imaging of Focal and Diffuse Fibrosing Mediastinitis.

Fibrosing mediastinitis is a rare benign but potentially life-threatening process that occurs because of proliferation of fibrotic tissue in the mediastinum. The focal subtype is more common and typically is associated with an abnormal immunologic response to Histoplasma capsulatum infection. Affected patients are typically young at presentation, but a wide age range has been reported, without a predilection for either sex. The diffuse form may be idiopathic or associated with autoimmunity, usually affects middle-aged and/or elderly patients, and is more common in men. For both subtypes, patients present with signs and symptoms related to obstruction or compression of vital mediastinal structures. The most common presenting signs and symptoms are cough, dyspnea, recurrent pneumonia, hemoptysis, and pleuritic chest pain. Patients with the diffuse subtype may have additional extrathoracic symptoms depending on the other organ systems involved. Because symptom severity is variable, treatment should be individualized with therapies tailored to alleviate compression of the affected mediastinal structures. Characteristic imaging features of fibrosing mediastinitis include infiltrative mediastinal soft tissue (with or without calcification) with compression or obstruction of mediastinal vascular structures and/or the aerodigestive tract. When identified in the appropriate clinical setting, these characteristic features allow the radiologist to suggest the diagnosis of fibrosing mediastinitis. Careful assessment is crucial at initial and follow-up imaging for exclusion of underlying malignancy, assessment of disease progression, identification of complications, and evaluation of treatment response. Online supplemental material is available for this article. ©RSNA, 2019.

Training-induced changes on quadriceps muscle oxygenation measured by near-infrared spectroscopy in healthy subjects and in chronic obstructive pulmonary disease patients.

AIM: We hypothesize that training-induced changes in muscle oxygen saturation (StO2 ) assessed by near-infrared spectroscopy (NIRS) during constant work rate cycling exercise (CWRE) may be a useful marker of the effects of training at 'vastus medialis' of the quadriceps in patients with chronic obstructive pulmonary disease (COPD). METHODS: Incremental exercise [peak oxygen uptake (VO2 )] and CWRE at 70% pretraining peak VO2 , before and after 8-w training, were done in 10 healthy age-matched subjects (H) [80% men, 65(11) years, FEV1 105(14)%] and 16 COPD patients [94% men, 70(5) years, FEV1 46(11) %] encompassing the entire spectrum of disease severity, recruited in the outpatient clinics. NIRS was used to assess StO2 in the 'vastus medialis' of the left quadriceps. RESULTS: Pretraining CWRE decreased StO2 (P<0·05) and generated marked StO2 rebound (P<0·001) after unloading in the two groups. After training, VO2 peak increased in H [253(204) ml min-1 ] (P<0·01) and in COPD [180(183) ml·min-1 ] (P = 0·01) and blood lactate fell [-4·4 (2·7) and -1·6(2·3) mmol·m-1 ] (P<0·05 each). Training generated a further fall in StO2 during CWRE [-10(12)% and -10(10)%, P<0·05] and increased StO2 rebound after unloading [8(7)% and 5(9)%, P<0·05] in both groups. CONCLUSION: Endurance training further decreased StO2 during CWRE, similarly in both groups, likely due to training-induced enhancement of muscle O2 transfer and utilization. Training-induced StO2 fall during CWRE may be useful individual marker for non-invasive assessment of enhanced muscle aerobic post-training function.

Physical activity in people with asbestos related pleural disease and dust-related interstitial lung disease: An observational study.

This study aimed to measure the levels of physical activity (PA) in people with dust-related pleural and interstitial lung diseases and to compare these levels of PA to a healthy population. There is limited data on PA in this patient population and no previous studies have compared PA in people with dust-related respiratory diseases to a healthy control group. Participants with a diagnosis of a dust-related respiratory disease including asbestosis and asbestos related pleural disease (ARPD) and a healthy age- and gender-matched population wore the SenseWear(®) Pro3 armband for 9 days. Six-minute walk distance, Medical Outcomes Study 36-item short-form health survey and the Hospital Anxiety and Depression Scale were also measured. Fifty participants were recruited and 46 completed the study; 22 with ARPD, 10 with dust-related interstitial lung disease (ILD) and 14 healthy age-matched participants. The mean (standard deviation) steps/day were 6097 (1939) steps/day for dust-related ILD, 9150 (3392) steps/day for ARPD and 10,630 (3465) steps/day for healthy participants. Compared with the healthy participants, dust-related ILD participants were significantly less active as measured by steps/day ((mean difference 4533 steps/day (95% confidence interval (CI): 1888-7178)) and energy expenditure, ((mean difference 512 calories (95% CI: 196-827)) and spent significantly less time engaging in moderate, vigorous or very vigorous activities (i.e. >3 metabolic equivalents; mean difference 1.2 hours/day (95% CI: 0.4-2.0)). There were no differences in levels of PA between healthy participants and those with ARPD. PA was reduced in people with dust-related ILD but not those with ARPD when compared with healthy age and gender-matched individuals.

Right Ventricular Mass is Associated with Exercise Capacity in Adults with Repaired Tetralogy of Fallot.

The relationship between exercise capacity and right ventricular (RV) structure and function in adult repaired tetralogy of Fallot (TOF) is poorly understood. We therefore aimed to examine the relationships between cardiac MRI and cardiopulmonary exercise test variables in adult repaired TOF patients. In particular, we sought to determine the role of RV mass in determining exercise capacity. Eighty-two adult repaired TOF patients (age at evaluation 26 ± 10 years; mean age at repair 2.5 ± 2.8 years; 23.3 ± 7.9 years since repair; 53 males) (including nine patients with tetralogy-type pulmonary atresia with ventricular septal defect) were prospectively recruited to undergo cardiac MRI and cardiopulmonary exercise testing. As expected, these repaired TOF patients had RV dilatation (indexed RV end-diastolic volume: 153 ± 43.9 mL/m(2)), moderate-severe pulmonary regurgitation (pulmonary regurgitant fraction: 33 ± 14 %) and preserved left (LV ejection fraction: 59 ± 8 %) and RV systolic function (RV ejection fraction: 51 ± 7 %). Exercise capacity was near-normal (peak work: 88 ± 17 % predicted; peak oxygen consumption: 84 ± 17 % predicted). Peak work exhibited a significant positive correlation with RV mass in univariate analysis (r = 0.45, p < 0.001) and (independent of other cardiac MRI variables) in multivariate analyses. For each 10 g higher RV mass, peak work was 8 W higher. Peak work exhibits a significant positive correlation with RV mass, independent of other cardiac MRI variables. RV mass measured on cardiac MRI may provide a novel marker of clinical progress in adult patients with repaired TOF.

Dobutamine stress for evaluation of right ventricular reserve in pulmonary arterial hypertension.

Right ventricular contractile response to pharmacological stress in pulmonary arterial hypertension (PAH) has not been characterised. We evaluated right ventricular contractile reserve in adults with PAH using dobutamine stress echocardiography. 16 PAH patients and 18 age-matched controls underwent low-dose dobutamine stress echocardiography. Contractile reserve was assessed by the change (Δ; peak stress minus rest value) in tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S'). A subgroup of 13 PAH patients underwent treadmill cardiopulmonary exercise testing for peak oxygen uptake (V'O2peak). At rest, TAPSE and S' were reduced in the PAH group compared with controls (1.7 ± 0.4 versus 2.4 ± 0.2 cm and 9.7 ± 2.6 versus 12.5 ± 1.2 cm · s(-1), respectively; p<0.05). Contractile reserve was markedly attenuated in PAH compared to controls (ΔTAPSE 0.1 ± 0.2 versus 0.6 ± 0.3 cm and ΔS' 4.6 ± 2.8 versus 11.2 ± 3.6 cm · s(-1); p<0.0001). In the sub-group of PAH patients with preserved right ventricular systolic function at rest, contractile reserve remained depressed compared to controls. V'O2peak was significantly correlated with ΔS' (r=0.87, p=0.0003) and change in stroke volume (r=0.59, p=0.03). Dobutamine stress can reveal sub-clinical reduction in right ventricular contractile reserve in patients with PAH. A correlation with exercise capacity suggests potential clinical value beyond resting measurements.

Mechanisms of maintained exercise capacity in adults with repaired tetralogy of Fallot.

BACKGROUND: The mechanisms whereby cardiac output is augmented with exercise in adult repaired tetralogy of Fallot (TOF) are poorly characterised. METHODS: 16 repaired TOF patients (25 ± 7 years of age) and 8 age and sex matched controls (25 ± 4 years of age) underwent cardiopulmonary exercise testing and then real-time cardiac MRI (1.5 T) at rest and whilst exercising within the scanner, aiming for 30% heart rate reserve (Level 1) and 60% heart rate reserve (Level 2), using a custom-built MRI compatible foot pedal device. RESULTS: At rest, TOF patients had severely dilated RVs (indexed RV end-diastolic volume: 149 ± 37 mL/m(2)), moderate-severe PR (regurgitant fraction 35 ± 12%), normal RV fractional area change (FAC) (52 ± 7%) and very mildly impaired exercise capacity (83 ± 15% of predicted maximal work rate). Heart rate and RV FAC increased significantly in TOF patients (75 ± 10 vs 123 ± 17 beats per minute, p<0.001; 44 ± 7 vs 51 ± 10%, p=0.025), and similarly in control subjects (70 ± 11 vs 127 ± 12 beats per minute, p<0.001; 49 ± 7 vs 61 ± 9%, p=0.003), when rest was compared to Level 2. PR fraction decreased significantly but only modestly, from rest to Level 2 in TOF patients (37 ± 15 to 31 ± 15%, p=0.002). Pulmonary artery net forward flow was maintained and did not significantly increase from rest to Level 2 in TOF patients (70 ± 19 vs 69 ± 12 mL/beat, p=0.854) or controls (93 ± 9 vs 95 ± 21 mL/beat, p=0.648). CONCLUSIONS: During exercise in repaired TOF subjects with dilated RV and free PR, increased total RV output per minute was facilitated by an increase in heart rate, an increase in RV FAC and a decrease in PR fraction.

Exercise training for asbestos-related and other dust-related respiratory diseases: a randomised controlled trial.

BACKGROUND: The study aimed to determine the short and long-term effects of exercise training on exercise capacity and health-related quality of life (HRQoL) compared to usual care in people with dust-related pleural and interstitial respiratory diseases. No previous studies have specifically evaluated exercise training in this patient population. METHODS: Participants with a diagnosis of a dust-related respiratory disease including asbestosis and asbestos related pleural disease were recruited and randomised to an eight-week exercise training group (EG) or a control group (CG) of usual care. Six-minute walk distance (6MWD), St George's Respiratory Questionnaire (SGRQ) and Chronic Respiratory Disease Questionnaire (CRQ) were measured at baseline, eight weeks and 26 weeks by an assessor blinded to group allocation. RESULTS: Thirty-three of 35 male participants completed the study. Sixty-nine percent of participants had asbestos related pleural disease. At eight weeks, compared to the CG, the EG showed a significantly increased 6MWD (mean difference (95%CI)) 53 metres (32 to 74), improved SGRQ total score, -7 points (-13 to -1) and increased CRQ total score, 6.4 points (2.1 to 10.7). At 26 weeks significant between-group differences were maintained in 6MWD, 45 metres (17 to 73) and CRQ total score, 13.1 points (5.2 to 20.9). CONCLUSION: Exercise training improved short and long-term exercise capacity and HRQoL in people with dust-related pleural and interstitial respiratory diseases. CLINICAL TRIAL REGISTRATION NUMBER: ANZCTR12608000147381. Date trial registered: 27.03.2008.

Right ventricular outflow tract enlargement prior to pulmonary valve replacement is associated with poorer structural and functional outcomes, in adults with repaired Tetralogy of Fallot.

BACKGROUND: Pulmonary valve replacement (PVR) is commonly performed late after Tetralogy of Fallot (TOF) repair. We examined the effects of PVR on cardiac structure, function and exercise capacity in adults with repaired TOF. METHODS: Eighteen adult patients with repaired TOF and severe pulmonary regurgitation (PR) with right ventricular (RV) dilatation requiring PVR for clinical reasons (age; 25±8 years) were recruited to undergo cardiac MRI (1.5T) and cardiopulmonary exercise testing before and 14±3 months after PVR. RESULTS: Reduced indexed RV end-diastolic volume (RVEDVi; 186±32mL/m(2) pre-op vs 114±20mL/m(2) post-op, p<0.001) was observed after PVR. "Normalisation" of RVEDVi (≤108mL/m(2)) was achieved in only seven of 18 patients. Pre-PVR RVEDVi correlated with post-operative change in RVEDVi (change=-72.1±20.4mL/m(2), r=-0.815, p<0.001). Exercise capacity remained high-normal post-PVR (% predicted maximal workload: 93±16% vs 91±12%, p=0.5). Regional RV volumes were assessed; RV outflow tract (RVOT) volumes were compared to the RV muscular corpus. Large pre-PVR RVOT volumes correlated negatively with post-surgical RV ejection fraction, peak VO2 and delta VO2 at anaerobic threshold (p<0.05 for all). CONCLUSIONS: Normalisation of RV volume is unlikely to be achieved above a pre-PVR RVEDVi of 165mL/m(2) or more. In particular, an enlarged RVOT prior to PVR predicts suboptimal structural and functional outcomes.

Functional exercise capacity and health-related quality of life in people with asbestos related pleural disease: an observational study.

BACKGROUND: Functional exercise capacity in people with asbestos related pleural disease (ARPD) is unknown and there are no data on health-related quality of life (HRQoL). The primary aims were to determine whether functional exercise capacity and HRQoL were reduced in people with ARPD. The secondary aim was to determine whether functional exercise capacity was related to peak exercise capacity, HRQoL, physical activity or respiratory function. METHODS: In participants with ARPD, exercise capacity was measured by the six-minute walk test (6MWT) and incremental cycle test (ICT); HRQoL by the St George's Respiratory Questionnaire and physical activity by an activity monitor worn for one week. Participants also underwent lung function testing. RESULTS: 25 males completed the study with a mean (SD) age of 71 (6) years, FVC 82 (19)% predicted, FEV1/FVC 66 (11)%, TLC 80 (19)% predicted and DLCO 59 (13)% predicted. Participants had reduced exercise capacity demonstrated by six-minute walk distance (6MWD) of 76 (11)% predicted and peak work rate of 71 (21)% predicted. HRQoL was also reduced. The 6MWD correlated with peak work rate (r=0.58, p=0.002), St George's Respiratory Questionnaire Total score (r=-0.57, p=0.003), metabolic equivalents from the activity monitor (r=0.45, p<0.05), and FVC % predicted (r=0.52, p<0.01). CONCLUSIONS: People with ARPD have reduced exercise capacity and HRQoL. The 6MWT may be a useful surrogate measure of peak exercise capacity and physical activity levels in the absence of cardiopulmonary exercise testing and activity monitors. TRIAL REGISTRATION: ANZCTR12608000147381.

Exercise capacity and stroke volume are preserved late after tetralogy repair, despite severe right ventricular dilatation.

OBJECTIVES: To assess if exercise capacity and resting stroke volume are different in tetralogy of Fallot (TOF) repair survivors with indexed RV (right ventricle) end-diastolic volume (RVEDVi) more versus less than 150 ml/m(2), a currently suggested threshold for pulmonary valve replacement (PVR). DESIGN: Cross-sectional study. SETTING: Single-centre adult congenital heart disease unit. PATIENTS: 55 consecutively eligible patients with repaired TOF (age at repair 2.3±1.9 years; age at evaluation 26.2±8.8 years; NYHA Class I or II). INTERVENTIONS: Cardiovascular MRI (1.5T) and cardiopulmonary exercise test. MAIN OUTCOME MEASURES: Biventricular volumes and function; exercise capacity. RESULTS: 20 patients had RVEDVi below, and 35 had RVEDVi above 150 ml/m(2), at time of referral. In the >150 ml/m(2) group, fractional pulmonary regurgitation was higher (41±8 vs 31±8%, p<0.001). Although RV ejection fraction (EF) was lower (47±7 vs 54±6%, p=0.007), indexed RV stroke volume was higher (87±14 vs 64±10 ml/m(2), p<0.001) in the >150 ml/m(2) group. There were no significant differences in LVEF, indexed LV stroke volume or exercise capacity (% predicted peak work: 90±17 vs 89±11% and; % predicted VO(2) peak: 84±17 vs 87±12%). CONCLUSIONS: Exercise capacity and stroke volume are maintained with RVEDVi above compared with below a commonly used cut-off for PVR surgery. Optimal timing for PVR, thus, remains unclear.

Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

RATIONALE: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. OBJECTIVES: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH. METHODS: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration. MEASUREMENTS AND MAIN RESULTS: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline. CONCLUSIONS: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

Pulmonary gas exchange response to exercise- and mannitol-induced bronchoconstriction in mild asthma.

Both exercise (EIB) and mannitol challenges were performed in asthmatic patients to assess and compare their pulmonary gas exchange responses for an equivalent degree of bronchoconstriction. In 11 subjects with EIB [27 +/- 4 (SD) yr; forced expiratory volume in 1 s (FEV(1)), 86 +/- 8% predicted], ventilation-perfusion (Va/Q) distributions (using multiple inert gas elimination technique) were measured 5, 15, and 45 min after cycling exercise (FEV(1) fall, 35 +/- 12%) and after mannitol (33 +/- 10%), 1 wk apart. Five minutes after EIB, minute ventilation (Ve; by 123 +/- 60%), cardiac output (Qt, by 48 +/- 29%), and oxygen uptake (Vo2; by 54 +/- 25%) increased, whereas arterial Po2 (Pa(O2); by 14 +/- 11 Torr) decreased due to moderate Va/Q imbalance, assessed by increases in dispersions of pulmonary blood flow (log SD(Q); by 0.53 +/- 0.16) and alveolar ventilation (log SD(V); by 0.28 +/- 0.15) (dimensionless) (P < 0.01 each). In contrast, for an equivalent degree of bronchoconstriction and minor increases in Ve, Qt, and Vo2, mannitol decreased Pa(O2) more intensely (by 24 +/- 9 Torr) despite fewer disturbances in log SDQ (by 0.27 +/- 0.12). Notwithstanding, mannitol-induced increase in log SDV at 5 min (by 0.35 +/- 0.15) was similar to that observed during EIB, as was the slow recovery in log SD(V) and high Va/Q ratio areas, at variance with the faster recovery of log SD(Q) and low Va/Q ratio areas. In asthmatic individuals, EIB provokes more Va/Q imbalance but less hypoxemia than mannitol, primarily due to postexercise increases in Ve and Qt benefiting Pa(O2). Va/Q inequalities during both challenges most likely reflect uneven airway narrowing and blood flow redistribution generating distinctive Va/Q patterns, including the development of areas with low and high Va/Q ratios.