Verification of an intravenous fluid warmer: A prospective, two-center observational trial.

Objectives: Avoiding inadvertent hypothermia during surgery is important. Intravenous fluid warmers used intraoperatively are critical for maintaining euthermia. We sought to prospectively evaluate the performance of the parylene-coated enFlow™ intravenous fluid warmer in patients undergoing surgery. Methods: This was a prospective two-center observational clinical trial performed in inpatient surgical services of two large academic hospital systems. After written informed consent, patients were enrolled in the trial. All patients were adults scheduled for a surgery that was expected to last for at least 1 h with the administration of at least 1 L of fluid warmed prior to infusion. Patient temperature was recorded in the preoperative unit, at the induction of anesthesia, and then every 15 or 30 min until the end of surgery. Temperature monitoring continued in the recovery unit. The parylene-coated enFlow™ intravenous fluid warmer was used in addition to the usual patient warming techniques. The primary outcome was the average core temperature, and secondary analyses assessed individual temperature measurements, temperature measurements during specific time periods, and rate of hypothermic events. Results: In all, 50 patients (29 males) with a mean age of 64 years were included in the analysis. The mean surgical time was 195 min and patients received an average of 1142 mL of fluids. Core temperature dropped by only 0.3°C approximately 60 min after induction and recovered back to the baseline level approximately 60 min later. There was no correlation between flow rate and measured core body temperature. Conclusions: The parylene-coated enFlow intravenous fluid warmer was able to warm fluids at all flow rates during prolonged surgery. The results showed that enFlow performed as expected.

Levels of leachable elements from long-term use of enFlow fluid warmer.

Objective: In the delivery of intravenous fluids, in-line warming devices frequently transfer heat using a metal heating plate, which if uncoated can risk elution. This bench study examined extractable elements detected following long-term use of the parylene-coated enFlow® Disposable IV/Blood Warmer. Methods: We tested 16 clinically relevant challenge fluids typical of the surgical setting, including commercially available single donor blood and blood products as well as intravenous saline and electrolyte solutions. After 72 h of warming at 40°C (104°F) via the enFlow, analytical chemistry identified and quantified the most clinically significant extractable elements (arsenic, barium, cadmium, copper, and lead) to estimate chemical exposure. We also measured the extracted concentrations of these five elements following simulated use of the device with three solutions (Sterofundin ISO, Plasma-Lyte 148, and whole blood) that were pumped through the warmed device at two different flow rates (0.2 and 5.5 mL min-1). Results: Across all scenarios of acute and long-term exposures for different populations, the enFlow demonstrated low toxicological risks as measured by the calculation of tolerable exposure for extracted arsenic, barium, cadmium, copper, and lead. Conclusion: The results suggest biological safety for the use of parylene-coated enFlow with a variety of intravenous solutions and in different therapeutic scenarios.

Impact of parylene coating on heating performance of intravenous fluid warmer: a bench study.

BACKGROUND: Perioperative hypothermia is a common occurrence, particularly with the elderly and pediatric age groups. Hypothermia is associated with an increased risk of perioperative complications. One method of preventing hypothermia is warming the infused fluids given during surgery. The enFlow™ intravenous fluid warmer has recently been reintroduced with a parylene coating on its heating blocks. In this paper, we evaluated the impact of the parylene coating on the new enFlow's fluid warming capacity. METHODS: Six coated and six uncoated enFlow cartridges were used. A solution of 10% propylene glycol and 90% distilled H2O was infused into each heating cartridge at flow rates of 2, 10, 50, 150, and 200 ml/min. The infused fluid temperature was set at 4 °C, 20 °C, and 37 °C. Output temperature was recorded at each level. Data for analysis was derived from 18 runs at each flow rate (six cartridges at three temperatures). RESULTS: The parylene coated fluid warming cartridge delivered very stable output of 40 °C temperatures at flow rates of 2, 10, and 50 ml/min regardless of the temperature of the infusate. At higher flow rates, the cartridges were not able to achieve the target temperature with the colder fluid. Both cartridges performed with similar efficacy across all flow rates at all temperatures. CONCLUSIONS: At low flow rates, the parylene coated enFlow cartridges was comparable to the original uncoated cartridges. At higher flow rates, the coated and uncoated cartridges were not able to achieve the target temperature. The parylene coating on the aluminum heating blocks of the new enFlow intravenous fluid warmer does not negatively affect its performance compared to the uncoated model.

Observation of Aerosol Generation by Human Subjects During Cardiopulmonary Exercise Testing Using a High-Powered Laser Technique: A Pilot Project.

Purpose: Human respiratory aerosols may have important implications for transmission of pathogens. The study of aerosol production during vigorous breathing activities such as exercise is limited. In particular, data on aerosol production during cardiopulmonary exercise testing (CPET) are lacking. Methods: In this pilot project, we used a high-powered, pulsed Nd:YAG laser to illuminate a region of interest in front of two healthy adult subjects during CPET. Subjects exercised to the point of respiratory compensation. Images were captured with a high-speed, high-resolution camera to determine net exhaled particle (NEP) counts at different phases of CPET, including resting breathing, submaximal exercise, peak exercise, and active recovery. Experiments were performed with the room ventilation activated. Results: Net exhaled particle counts remained relatively constant until late/peak exercise when they decreased prior to rebounding into recovery. NEP counts at resting breathing were higher than those reported using other methods of measurement. Exhaled particles were in the submicron size range. Conclusion: Our method of aerosol particle quantification enables measurement of significant quantities of ultrafine particles and dynamic assessment of aerosol production during CPET. The unique pattern of aerosol production observed during submaximal and peak exercise suggests that extension of results from resting breathing to CPET may not be appropriate.

Bisoprolol and/or hyperoxic breathing do not reduce hyperventilation in pulmonary arterial hypertension patients.

Hyperventilation is common in pulmonary arterial hypertension and may be related to autonomic imbalance. Patients underwent exercise testing and hyperoxic breathing before and after bisoprolol treatment. We found that neither beta blocker treatment nor hyperoxic breathing in patients reduced hyperventilation at rest and during exercise, although it reduced heart rate.

Comparison of Two Metabolic Simulators Used for Gas Exchange Verification in Cardiopulmonary Exercise Test Carts.

INTRODUCTION: Metabolic simulators (MS) produce simulated human breaths for the purpose of verification of cardiopulmonary exercise test (CPET) equipment. MS should produce consistent identical breaths with known CO2 and O2 gas concentrations over a range of breath rates and tidal volumes. Reliability of a CPET metabolic cart depends on ongoing quality control and maintenance of the device, including intermittent verification with a MS. We compared two MS devices against two standard CPET systems. METHODS: The Vacumed 17056 (Vacumetrics, Ventura, CA) and Relitech (Relitech Systems BV, Nijkerk, The Netherlands) were used with two standard metabolic carts (Vyntus CPX and Vyntus ONE, both Vyaire Medical, Mettawa, IL, United States). Tidal volume (VT) was set at 2 and 3 L and breathing frequency ranged from 20 to 80 breaths per minute for each MS. At each set point, we measured three sets of 40 breaths. Primary outcome parameters collected were VT, oxygen consumption ( v . O2), carbon dioxide production ( v . CO2), and respiratory exchange ratio (RER). RESULTS: VT, RER, v . O2, and v . CO2 results as obtained from both MS were all within the limits of acceptability, at both tidal volume settings, and all ventilatory rates. No significant trends were identified for either MS device. The Relitech MS produced tidal volumes that were closer to the target VT for both CPET carts at both VT and all rates, but the results of both MS were within acceptable ranges. CONCLUSION: Verification of CPET equipment using either the VM or RT metabolic simulator, producing highly accurate and predictable simulated breaths of known composition, enabling CPET laboratory managers to rely on subject test data obtained during cardiopulmonary exercise testing.

Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents.

OBJECTIVES: To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. STUDY DESIGN: Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. RESULTS: We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. CONCLUSIONS: Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.

Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency.

UNLABELLED: In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal [Formula: see text] were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. ( TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01288651).

The effects of exercise on right ventricular contractility and right ventricular-arterial coupling in pulmonary hypertension.

RATIONALE: Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility. OBJECTIVES: To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exercise response in end-systolic elastance (ΔEes), and the effects of exercise on the matching of Ees and RV afterload (Ea) (i.e., RV-arterial coupling; Ees/Ea). In addition, we compared ΔEes with a recently proposed surrogate, the rest-to-exercise change in pulmonary artery pressure (ΔPAP). METHODS: We prospectively included 17 patients with precapillary PH and 7 control subjects without PH who performed a submaximal invasive cardiopulmonary exercise test between January 2013 and July 2014. Ees and Ees/Ea were assessed using single-beat pressure-volume loop analysis. MEASUREMENTS AND MAIN RESULTS: Exercise data in 16 patients with PH and 5 control subjects were of sufficient quality for analysis. Ees significantly increased from rest to exercise in control subjects but not in patients with PH. Ea significantly increased in both groups. As a result, exercise led to a decrease in Ees/Ea in patients with PH, whereas Ees/Ea was unaffected in control subjects (Pinteraction = 0.009). In patients with PH, ΔPAP was not related to ΔEes but significantly correlated to the rest-to-exercise change in heart rate. CONCLUSIONS: In contrast to control subjects, patients with PH were unable to increase Ees during submaximal exercise. Failure to compensate for the further increase in Ea during exercise led to deterioration in Ees/Ea. Furthermore, ΔPAP did not reflect ΔEes but rather the change in heart rate.

Myocardial efficiency is an important determinant of functional improvement after aortic valve replacement in aortic valve stenosis patients: a combined PET and CMR study.

AIMS: The pathophysiology underlying aortic valve stenosis (AVS)-induced cardiac dysfunction and reduced exercise capacity is unclear. We hypothesize that improvement of myocardial external efficiency (MEE)--the ratio between external work and myocardial oxygen consumption (MVO2)--underlies functional improvement of AVS patients after aortic valve replacement (AVR). Therefore, the aim of this proof-of-concept study was to investigate whether myocardial efficiency is reduced in patients with cardiac hypertrophy caused by AVS and to assess the effect of AVR on myocardial efficiency in relation to exercise capacity. METHODS AND RESULTS: Echocardiography, cardiopulmonary exercise test, [(11)C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging were performed in 10 AVS patients prior to (pre-AVR) and 4 months after AVR (post-AVR). Fourteen healthy individuals served as control group. MEE was significantly lower in pre-AVR patients (32 ± 7%) than in controls (49 ± 6%). AVR significantly decreased left ventricle mass and MVO2. Also, external work significantly decreased post-AVR reaching similar values as in controls. AVR significantly improved MEE from 32 ± 7 to 37 ± 5% (P = 0.02). Moreover, significant correlations were present between the AVR-induced increase in MEE and changes in both exercise work (r = 0.74, P = 0.01) and peak VO2 (r = 0.67, P = 0.03). However, four AVS patients did not show improved MEE, which was associated with no or minimal improvement in exercise parameters. CONCLUSION: MEE is significantly reduced in patients with AVS-induced hypertrophy. Improved MEE is an important predictor of AVR-induced improvement of exercise capacity in AVS patients. Future investigation is needed to confirm our observations in a large prospective, multicenter clinical trial.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Prognostic relevance of changes in exercise test variables in pulmonary arterial hypertension.

INTRODUCTION: Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent changes in these exercise variables reflect improvements in survival. The aim of this study was to determine changes in exercise variables in PAH patients and to relate these changes to survival. METHODS: Baseline cardiopulmonary exercise test (CPET) variables and six-minute-walk-distance (6MWD) were available from 65 idiopathic PAH patients (50 females; mean age 45±2yrs). The same variables were determined after treatment (13months) in a sub group of 43 patients. To estimate the association between changes in exercise variables and changes in cardiac function, right-ventricle ejection fraction (RVEF) was measured by cardiac MRI at baseline and after treatment in 34 patients. Mean follow-up time after the second CPET was 53 (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to baseline and treatment-associated changes in exercise variables. RESULTS: Survivors showed a significantly greater change in maximal oxygen uptake than non-survivors and this change in aerobic capacity was significantly related to changes in RVEF. From baseline until the end of the study period, two patients underwent a lung transplantation and 19 patients died. Survival analysis showed that baseline 6MWD (p<0.0001), maximal heart rate (p<0.0001) and the slope relating ventilation with carbon dioxide production (p≤0.05) were significant predictors of survival, whereas baseline oxygen uptake and oxygen pulse held no predictive value. Treatment associated changes in 6MWD (p<0.01), maximal heart rate (p<0.05), oxygen uptake (p<0.001) and oxygen pulse predicted survival (p<0.05), whereas changes in the slope relating ventilation with carbon dioxide production did not. CONCLUSION: Exercise variables with prognostic significance when determined at baseline, retain their prognostic relevance after treatment. However, when changes in exercise variables upon treatment are considered, a different set of variables provides prognostic information.

Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses.

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preserved DLCO. Retrospectively, 166 IPAH patients were included and grouped based on a DLCO cut-off value of 45% pred (IPAH(<45%) and IPAH(≥45%)). Clinical characteristics, treatment responses and survival were compared. IPAH(<45%) were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a low DLCO. Age and number of pack years were independently associated with DLCO < 45% pred. IPAH(<45%) showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease. To conclude, a severely reduced DLCO in IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.

Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH. METHODS: Forty-seven patients, GOLD (Global Initiative for Chronic Obstructive Lung Disease)stages II to IV, underwent cardiopulmonary exercise testing and right-sided heart catheterization at rest and during exercise. Patients were divided into three groups based on mean pulmonary artery pressure (mPAP) at rest: no PH (mPAP, < 25 mm Hg), moderate PH (mPAP, 25-39 mm Hg),and severe PH (mPAP, ≥ 40 mm Hg). Mixed venous oxygen saturation (S VO 2 ) was used for evaluating the circulatory reserve. Pa CO 2 and the calculated breathing reserve were used for evaluation of the ventilatory reserve. RESULTS: Patients without PH (n = 24) had an end-exercise S VO 2 of 48%± 9%, an increasing Pa CO 2 with exercise, and a breathing reserve of 22% ± 20%. Patients with moderate PH (n = 14) had an exercise S VO 2 of 40% ± 8%, an increasing Pa CO 2 , and a breathing reserve of 26% ± 15%. Patients with severe PH (n =9) had a significantly lower end-exercise S VO 2 (30% ± 6%), a breathing reserve of 37% ± 11%, and an absence of Pa CO 2 accumulation. CONCLUSION: Patients with severe PH showed an exhausted circulatory reserve at the end of exercise.A profile of circulatory reserve in combination with ventilatory impairments was found inpatients with COPD and moderate or no PH. The results suggest that pulmonary vasodilation might only improve exercise tolerance in patients with COPD and severe PH.

Exercise pathophysiology in patients with chronic mountain sickness exercise in chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. METHODS: Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. RESULTS: The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). CONCLUSIONS: The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients.

INTRODUCTION: It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure. METHODS: Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output. RESULTS: Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure. CONCLUSIONS: We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.

Usefulness of serial N-terminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension.

Previous studies have shown the prognostic benefit of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in pulmonary arterial hypertension (PAH) at time of diagnosis. However, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-pro-BNP in PAH. This study examined the value of serial NT-pro-BNP measurements in predicting prognosis PAH. We retrospectively analyzed all available NT-pro-BNP plasma samples in 198 patients who were diagnosed with World Health Organization group I PAH from January 2002 through January 2009. At time of diagnosis median NT-pro-BNP levels were significantly different between survivors (610 pg/ml, range 6 to 8,714) and nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT-pro-BNP was significantly associated (p <0.001) with other parameters of disease severity (6-minute walking distance, functional class). Receiver operating curve analysis identified ≥1,256 pg/ml as the optimal NT-pro-BNP cutoff for predicting mortality at time of diagnosis. Serial measurements allowed calculation of baseline NT-pro-BNP (i.e., intercept obtained by back-extrapolation of concentration-time graph), providing a better discrimination between survivors and nonsurvivors than NT-pro-BNP at time of diagnosis alone (p = 0.010). Furthermore, a decrease of NT-pro-BNP of >15%/year was associated with survival. In conclusion, a serum NT-pro-BNP level ≥1,256 pg/ml at time of diagnosis identifies poor outcome in patients with PAH. In addition, a decrease in NT-pro-BNP of >15%/year is associated with survival in PAH.

Smallest detectable change in volume differs between mass flow sensor and pneumotachograph.

BACKGROUND: To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph. METHOD: In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2. FINDINGS: The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (p = 0.04), DLCO (in mmol*kPa-1*min-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (p = 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (p = 0.04) and DLCO/VA (in mmol*kPa-1*min-1*L-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (p = 0.79). CONCLUSIONS: Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.

Exercise stroke volume and heart rate response differ in right and left heart failure.

AIMS: In pulmonary arterial hypertension (PAH), the exercise-induced increase in stroke volume (SV) is limited by the increase in pulmonary artery pressure. In left heart failure (LHF), systemic arterial pressure increases little during exercise, and the SV increase is limited by the left ventricle itself. These differences might be reflected by a dissimilar SV and heart rate (HR) response to exercise, which could have important therapeutic implications, for example in beta-blocker therapy. Therefore, we tested the hypothesis that SV and HR responses during exercise are different between PAH and LHF patients. METHODS AND RESULTS: We included 28 PAH and 18 LHF patients (recruited from the heart failure unit) matched on a maximal oxygen uptake of <15 mL/kg/min, who were referred to our Pulmonary Function Department between 2000 and 2008 for a maximal cardio-pulmonary exercise test. Only patients who had not been exposed to beta-blockers were included. Pulmonary arterial hypertension and LHF patient groups had equally impaired exercise tolerance (about 42% of predicted) with a maximal oxygen uptake of 0.80 +/- 0.29 and 0.86 +/- 0.19 L/min. The peak SV response to exercise was significantly lower in PAH patients (-14 mL, P = 0.01); this was compensated by a steeper slope of HR relating to oxygen uptake (0.03 beats/mL, P = 0.001). CONCLUSION: We conclude that PAH patients have a smaller SV response, but a larger HR response than LHF patients.

Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study.

BACKGROUND: There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. METHODS: Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT. RESULTS: TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 +/- 7% vs. 63 +/- 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 +/- 6% vs. 39 +/- 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0-25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0-21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups. CONCLUSION: SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.