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Introduction: In recent years, ventilatory efficiency (minute ventilation ( V ' E )/carbon dioxide production ( V ' CO 2 ) slope) and partial pressure of end-tidal carbon dioxide ( P ETCO 2 ) have emerged as independent predictors of postoperative pulmonary complications (PPC). Single parameters may give only partial information regarding periprocedural hazards. Accordingly, our aim was to create prediction models with improved ability to stratify PPC risk in patients scheduled for elective lung resection surgery., Methods: This post hoc analysis was comprised of consecutive lung resection candidates from two prior prospective trials. All individuals completed pulmonary function tests and cardiopulmonary exercise testing (CPET). Logistic regression analyses were used for identification of risk factors for PPC that were entered into the final risk prediction models. Two risk models were developed; the first used rest P ETCO 2 (for patients with no available CPET data), the second used V ' E / V ' CO 2 slope (for patients with available CPET data). Receiver operating characteristic analysis with the De-Long test and area under the curve (AUC) were used for comparison of models., Results: The dataset from 423 patients was randomly split into the derivation (n=310) and validation (n=113) cohorts. Two final models were developed, both including sex, thoracotomy, "atypical" resection and forced expiratory volume in 1 s/forced vital capacity ratio as risk factors. In addition, the first model also included rest P ETCO 2 , while the second model used V ' E / V ' CO 2 slope from CPET. AUCs of risk scores were 0.795 (95% CI: 0.739-0.851) and 0.793 (95% CI: 0.737-0.849); both p<0.001. No differences in AUCs were found between the derivation and validation cohorts., Conclusions: We created two multicomponental models for PPC risk prediction, both having excellent predictive properties., Competing Interests: Conflict of interest: K. Brat received lecture and consulting fees from Chiesi CZ, Boehringer Ingelheim CZ, Novartis CZ, AstraZeneca CZ and Angelini CZ, outside the submitted work. Conflict of interest: The other authors (I. Cundrle Jr, P. Homolka, M. Svoboda, L. Mitas, M. Plutinsky, Z. Chovanec and L.J. Olson) have nothing to disclose., (Copyright ©The authors 2024.)

Introduction: Post-operative oxygen therapy is used to prevent hypoxemia and surgical site infection. However, with improvements of anesthesia techniques, post-operative hypoxemia incidence is declining and the benefits of oxygen on surgical site infection have been questioned. Moreover, hyperoxemia might have adverse effects on the pulmonary and cardiovascular systems. We hypothesized hyperoxemia post thoracic surgery is associated with post-operative pulmonary and cardiovascular complications., Methods: Consecutive lung resection patients were included in this post-hoc analysis. Post-operative pulmonary and cardiovascular complications were prospectively assessed during the first 30 post-operative days, or hospital stay. Arterial blood gases were analyzed at 1, 6 and 12 h after surgery. Hyperoxemia was defined as arterial partial pressure of oxygen (PaO 2 )>100 mmHg. Patients with hyperoxemia duration in at least two adjacent time points were considered as hyperoxemic. Student t-test, Mann-Whitney U test and two-tailed Fisher exact test were used for group comparison. P values < 0.05 were considered statistically significant., Results: Three hundred sixty-three consecutive patients were included in this post-hoc analysis. Two hundred five patients (57%), were considered hyperoxemic and included in the hyperoxemia group. Patients in the hyperoxemia group had significantly higher PaO 2 at 1, 6 and 12 h after surgery (p < 0.05). Otherwise, there was no significant difference in age, sex, comorbidities, pulmonary function tests parameters, lung surgery procedure, incidence of post-operative pulmonary and cardiovascular complications, intensive care unit and hospital length of stay and 30-day mortality., Conclusion: Hyperoxemia after lung resection surgery is common and not associated with post-operative complications or 30-day mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Cardiopulmonary exercise testing parameters including ventilatory efficiency (V E /VCO 2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. V E /VCO 2 slope is closely related to the partial pressure of end-tidal carbon dioxide (P ET CO 2 ). We hypothesized P ET CO 2 at rest predicts postoperative pulmonary complications., Methods: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range)., Results: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. P ET CO 2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and V E /VCO 2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest P ET CO 2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and V E /VCO 2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest P ET CO 2 : AUC = 0.79 (95% CI 0.74-0.85); V E /VCO 2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48)., Conclusions: P ET CO 2 at rest has similar prognostic utility as V E /VCO 2 slope, suggesting rest P ET CO 2 may be used for postoperative pulmonary complications prediction in lung resection candidates., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: According to the guidelines for preoperative assessment of lung resection candidates, patients with normal forced expiratory volume in 1 s (FEV 1 ) and diffusing capacity of the lung for carbon monoxide ( D LCO ) are at low risk for post-operative pulmonary complications (PPC). However, PPC affect hospital length of stay and related healthcare costs. We aimed to assess risk of PPC for lung resection candidates with normal FEV 1 and D LCO (>80% predicted) and identify factors associated with PPC., Methods: 398 patients were prospectively studied at two centres between 2017 and 2021. PPC were recorded from the first 30 post-operative days. Subgroups of patients with and without PPC were compared and factors with significant difference were analysed by uni- and multivariate logistic regression., Results: 188 subjects had normal FEV 1 and D LCO . Of these, 17 patients (9%) developed PPC. Patients with PPC had significantly lower pressure of end-tidal carbon dioxide ( P ETCO 2 ) at rest (27.7 versus 29.9; p=0.033) and higher ventilatory efficiency ( V ' E / V ' CO 2 ) slope (31.1 versus 28; p=0.016) compared to those without PPC. Multivariate models showed association between resting P ETCO 2 (OR 0.872; p=0.035) and V ' E / V ' CO 2 slope (OR 1.116; p=0.03) and PPC. In both models, thoracotomy was strongly associated with PPC (OR 6.419; p=0.005 and OR 5.884; p=0.007, respectively). Peak oxygen consumption failed to predict PPC (p=0.917)., Conclusions: Resting P ETCO 2 adds incremental information for risk prediction of PPC in patients with normal FEV 1 and D LCO . We propose resting P ETCO 2 be an additional parameter to FEV 1 and D LCO for preoperative risk stratification., Competing Interests: Conflict of interests: M. Bratova received lecture and fees from Roche CZ, Bristol-Myers Squibb CZ and MSD CZ outside the submitted work. K. Brat received lecture and consulting fees from Chiesi CZ, Boehringer Ingelheim CZ, Novartis CZ, AstraZeneca CZ and Angelini CZ outside the submitted work. The other authors (I. Cundrle Jr, P. Homolka, M. Chobola, V. Sramek, Z. Merta, L. Mitas, M. Svoboda, Z. Chovanec and L.J. Olson) have nothing to disclose., (Copyright ©The authors 2023.)

Background: Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability and is commonly observed in patients with advanced heart failure (HF); it is associated with adverse prognosis. The goal of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score., Methods and Results: Consecutive patients with HF (N = 35) who underwent clinically indicated CRT, cardiopulmonary exercise testing and carbon dioxide (CO 2 ) chemosensitivity by rebreathe before and 4-6 months after CRT were included in this post hoc analysis. With CRT, EOV scores improved in 22 patients (63%). In these patients, left ventricular ejection fraction, left atrial volume, brain natriuretic peptide concentration, and CO 2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO 2 production significantly decreased, and end-tidal CO 2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO 2 chemosensitivity to be significantly associated with the improvement of the EOV score (b = 0.64; F = 11.3; P = 0.004). In the group without EOV score improvement (n = 13), though left ventricular ejection fraction significantly increased with CRT (P = 0.015), no significant changes in ventilation or gas exchange were observed., Conclusion: The EOV score was mitigated by CRT and was associated with decreased CO 2 chemosensitivity., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: One-lung ventilation (OLV) may be complicated by hypoxemia. Ventilatory efficiency, defined as the ratio of minute ventilation to carbon dioxide output (V E /VCO 2 ), is increased with ventilation/perfusion mismatch and pulmonary artery hypertension, both of which may be associated with hypoxemia. Hence, the authors hypothesized increased V E /VCO 2 will predict hypoxemia during OLV., Design: Prospective observational study., Setting: Single-center, university, tertiary care hospital., Participants: The study comprised 50 consecutive lung resection candidates., Interventions: All patients underwent cardiopulmonary exercise testing before surgery. Patients who required inspired oxygen fraction (F i O 2 ) ≥0.7 to maintain arterial oxygen (O 2 ) saturation >90% after 30 minutes of OLV were considered to be hypoxemic. The Student t or Mann-Whitney U test were used for comparison of patients who became hypoxemic and those who did not. Multiple regression analysis adjusted for age, sex, and body mass index was used to evaluate which parameters were associated with the V E /VCO 2 slope. Data are summarized as mean ± standard deviation., Measurements and Main Results: Twenty-four patients (48%) developed hypoxemia. There was no significant difference in age, sex, and body mass index between hypoxemic and nonhypoxemic patients. However, patients with hypoxemia had a significantly higher V E /VCO 2 slope (30 ± 5 v 27 ± 4; p = 0.04) with exercise and lower partial pressure of oxygen/F i O 2 (129 ± 92 v 168 ± 88; p = 0.01), higher mean positive end-expiratory pressure (6.6 ± 1.5 v 5.6 ± 0.9 cmH 2 O; p = 0.02), and lower mean pulse oximetry O 2 saturation/F i O 2 index (127 ± 20 v 174 ± 17; p < 0.01) during OLV. Multiple regression showed V E /VCO 2 to be independently associated with the mean pulse oximetry O 2 saturation/F i O 2 index (b = -0.28; F = 3.1; p = 0.05)., Conclusions: An increased V E /VCO 2 slope may predict hypoxemia development in patients who undergo OLV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The heart and lungs are intimately linked. Hence, impaired function of one organ may lead to changes in the other. Accordingly, heart failure is associated with airway obstruction, loss of lung volume, impaired gas exchange, and abnormal ventilatory control. Cardiopulmonary exercise testing is an excellent tool for evaluation of gas exchange and ventilatory control. Indeed, many parameters routinely measured during cardiopulmonary exercise testing, including the level of minute ventilation per unit of carbon dioxide production and the presence of exercise oscillatory ventilation, have been found to be strongly associated with prognosis in patients with heart failure., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Measurement of ventilatory efficiency, defined as minute ventilation per unit carbon dioxide production (VE/VCO2), by cardiopulmonary exercise testing (CPET) has been proposed as a screen for hyperventilation syndrome (HVS). However, increased VE/VCO2 may be associated with other disorders which need to be distinguished from HVS. A more specific marker of HVS by CPET would be clinically useful. We hypothesized ventilatory control during exercise is abnormal in patients with HVS., Methods: Patients who underwent CPET from years 2015 through 2017 were retrospectively identified and formed the study group. HVS was defined as dyspnea with respiratory alkalosis (pH >7.45) at peak exercise with absence of acute or chronic respiratory, heart or psychiatric disease. Healthy patients were selected as controls. For comparison the Student t-test or Mann-Whitney U test were used. Data are summarized as mean ± SD or median (IQR); p<0.05 was considered significant., Results: Twenty-nine patients with HVS were identified and 29 control subjects were selected. At rest, end-tidal carbon dioxide (PETCO2) was 27 mmHg (25-30) for HVS patients vs. 30 mmHg (28-32); in controls (p = 0.05). At peak exercise PETCO2 was also significantly lower (27 ± 4 mmHg vs. 35 ± 4 mmHg; p<0.01) and VE/VCO2 higher ((38 (35-43) vs. 31 (27-34); p<0.01)) in patients with HVS. In contrast to controls, there were minimal changes of PETCO2 (0.50 ± 5.26 mmHg vs. 6.2 ± 4.6 mmHg; p<0.01) and VE/VCO2 ((0.17 (-4.24-6.02) vs. -6.6 (-11.4-(-2.8)); p<0.01)) during exercise in patients with HVS. The absence of VE/VCO2 and PETCO2 change during exercise was specific for HVS (83% and 93%, respectively)., Conclusion: Absence of VE/VCO2 and PETCO2 change during exercise may identify patients with HVS., Competing Interests: The authors have declared that no competing interests exist.

Background: Pneumothorax (PTX) is one of the most common complications of transbronchial biopsy (TBB). Previous research suggests that upper pulmonary lobe TBB may be associated with increased risk of PTX development. The aim of this study was to compare the risk of PTX after TBB performed from different pulmonary lobes., Methods: All bronchoscopic records from the period January 1st, 2015 - December 31st, 2017 (from the Department of Respiratory Diseases, University Hospital Brno, Czech Republic) were retrospectively analyzed. Of the 3542 bronchoscopic records, 796 patients underwent TBB and were further analyzed. Basic demographic data, TBB procedure-related factors, smoking history and radiological features were analyzed. Furthermore, in patients who developed PTX, PTX onset, PTX symptoms, distribution of the abnormal radiological findings and duration of hospitalization were also analyzed., Results: Patients who developed PTX had significantly lower body mass index (BMI) and more than 4 samples taken during procedure (all p < 0.05). TBB performed from the left upper pulmonary lobe was associated with a significant risk of PTX development (OR 2.27; 95% CI 1.18-4.35; p = 0.02). On the contrary, TBB performed from the right lower lobe was associated with a significant reduction of risk of developing PTX (OR 0.47; 95% CI 0.22-0.98; p = 0.04). Logistic regression analysis showed BMI (OR 1.08; 95% CI 1.02-1.16; p = 0.01), left upper lobe as sampling site (OR 2.15; 95% CI 1.13-4.11; p = 0.02) and more than 4 samples taken (OR 1.91; 95% CI 1.04-3.49; p = 0.04) to be significantly associated with PTX development., Conclusions: We conclude that TBB from the left upper pulmonary lobe is associated with significantly increased risk of post-procedural PTX. The right lower pulmonary lobe seems to be the safest sampling site to perform TBB. In patients with diffuse-type pulmonary disease, TBB should be performed preferably from the right lower lobe in order to decrease the risk of post-procedural PTX.

Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission.

Low leptin concentration has been shown to be associated with central sleep apnea in heart failure patients. We hypothesized that low leptin concentration predicts central sleep apnea. Consecutive ambulatory New York Heart Association (NYHA) classes I-IV heart failure patients were studied prospectively, including measurement of serum leptin, echocardiography and polysomnography. Sleep apnea was defined by type (central/mixed/obstructive) and by apnea-hypopnea index ≥5 by polysomnography. Subjects were divided into four groups by polysomnography: (1) central sleep apnea, (2) mixed apnea, (3) no apnea and (4) obstructive sleep apnea. Fifty-six subjects were included. Eighteen subjects were diagnosed with central sleep apnea, 15 with mixed apnea, 12 with obstructive apnea and 11 with no sleep apnea. Leptin concentration was significantly lower in central sleep apnea compared to obstructive apnea (8 ± 10.7 ng mL -1 versus 19.7 ± 14.7 ng mL -1 , P ˂ 0.01) or no sleep apnea (8 ± 10.7 ng mL -1 versus 17.1 ± 8.4 ng mL -1 , P ˂ 0.01). Logistic regression showed leptin to be associated independently with central sleep apnea [odds ratio (OR): 0.19; 95% confidence interval (CI): 0.06-0.62; area under the curve (AUC): 0.80, P < 0.01]. For the detection of central sleep apnea, a cut-off value for leptin concentration 5 ng mL -1 yielded a sensitivity of 50% and specificity of 89%. In conclusion, a low leptin concentration may have utility for the screening of heart failure patients for central sleep apnea., (© 2017 European Sleep Research Society.)

Introduction: Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing and has been associated with major cardiovascular comorbidities. We hypothesized that the microcirculation is impaired in patients with OSA and that the magnitude of impairment correlates to OSA severity., Methods: Subjects were consecutive patients scheduled for routine diagnostic polysomnography (PSG). OSA was defined by paradoxical rib cage movements together with abdominal excursions and by the apnea-hypopnea index (AHI) (events/hour; no apnea AHI<5; mild apnea 5≤AHI<15; moderate apnea 15≤AHI<30; severe apnea AHI ≥30). Sidestream darkfield imaging was used to assess the sublingual microcirculation. Recordings of sublingual microcirculation (5 random sites) were performed before and after overnight PSG. Data are summarized as mean (±SD); p values <0.05 were considered statistically significant., Results: Thirty-three consecutive patients were included. OSA was diagnosed in 16 subjects (4 moderate, 12 severe). There was no significant difference in microcirculation between subjects with moderate OSA and without OSA. However, compared to subjects without OSA, subjects with severe OSA (AHI≥30) showed a significant decrease of microvascular flow index (-0.07±0.17 vs. 0.08±0.14; p = 0.02) and increase of microvascular flow index heterogeneity (0.06±0.15 vs. -0.06±0.11; p = 0.02) overnight. Multiple regression analysis (adjusted for age and gender) showed both decrease of flow and increase of flow heterogeneity associated with AHI (b = -0.41; F = 1.8; p = 0.04 and b = 0.43; F = 1.9; p = 0.03, respectively)., Conclusion: Acute overnight microcirculatory changes are observed in subjects with severe OSA characterized by decreased flow and increased flow heterogeneity.

Background: Leptin modulates ventilation and circulating levels are higher in normal women than men., Objectives: The aim of this study was to compare exercise ventilation and gas exchange in men and women with heart failure (HF) and their relation to circulating leptin concentration., Methods: Consecutive HF patients were studied by cardiopulmonary exercise testing and assay of circulating leptin concentration., Results: Fifty-seven men and 20 women were similar with respect to age, BMI, NYHA class, left ventricular ejection fraction, and peak oxygen consumption (all p > 0.05). Leptin concentration was lower (10.3 ± 10 vs. 25.3 ± 16 ng/mL; p < 0.01) and peak exercise ventilatory efficiency (V E /VCO 2 ) was higher (43 ± 10 vs. 36 ± 5; p < 0.01) in men. Leptin concentration was associated with peak exercise V E /VCO 2 (b = -0.35; F = 5.6; p = 0.02)., Conclusion: Men have significantly lower circulating leptin concentration and increased ventilatory drive during exercise than women with comparable HF. In men with HF, lower leptin concentration may account for an increased ventilatory drive., (Copyright © 2017. Published by Elsevier Inc.)

Background: Ventilatory efficiency (V˙e/V˙co 2 slope [minute ventilation to carbon dioxide output slope]) has been shown to predict morbidity and mortality in lung resection candidates. Patients with increased V˙e/V˙co 2 during exercise also exhibit an increased V˙e/V˙co 2 ratio and a decreased end-tidal CO 2 at rest. This study hypothesized that ventilatory values at rest predict respiratory complications and death in patients undergoing thoracic surgical procedures., Methods: Inclusion criteria for this retrospective, multicenter study were thoracotomy and cardiopulmonary exercise testing as part of routine preoperative assessment. Respiratory complications were assessed from the medical records (from the hospital stay or from the first 30 postoperative days). For comparisons, Student's t test or the Mann-Whitney U test was used. Logistic regression and receiver operating characteristic analyses were performed for evaluation of measurements associated with respiratory complications. Data are summarized as mean ± SD; p <0.05 is considered significant., Results: Seventy-six subjects were studied. Postoperatively, respiratory complications developed in 56 (74%) patients. Patients with postoperative respiratory complications had significantly lower resting tidal volume (0.8 ± 0.3 vs 0.9 ± 0.3L; p = 0.03), lower rest end-tidal CO 2 (28.1 ± 4.3vs 31.5 ± 4.2 mm Hg; p < 0.01), higher resting V˙e/V˙co 2 ratio (45.1 ± 7.1 vs 41.0 ± 6.4; p = 0.02), and higher V˙e/V˙co 2 slope (34.9 ± 6.4 vs 31.2 ± 4.3; p = 0.01). Logistic regression (age and sex adjusted) showed resting end-tidal CO 2 to be the best predictor of respiratory complications (odds ratio: 1.21; 95% confidence interval: 1.06 to 1.39; area under the curve: 0.77; p = 0.01)., Conclusions: Resting end-tidal CO 2 may identify patients at increased risk for postoperative respiratory complications of thoracic surgical procedures., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective/background: Obstructive sleep apnea (OSA) is highly prevalent and often undiagnosed in surgical patients. The aim of this study was to compare polygraphy (PG) performed on sedated patients during surgery to overnight polysomnography (PSG). It was hypothesized that perioperative PG may be used to diagnose OSA., Patients/methods: Overnight PSG was performed three days prior to surgery. For surgery, spinal anesthesia and sedation with propofol infusion were used. Sedation depth was monitored by the Bispectral index and maintained for all patients (target level 75). Echocardiography studies were available in three patients, and all were diagnosed with diastolic dysfunction. Relatively high prevalence of CSA in patients with diastolic dysfunction has been previously reported. During surgery, PG recording (Embletta) was performed. Sleep apnea was defined by the type (central/obstructive apnea ≥50%) and by the apnea-hypopnea index (AHI) (events/hour: AHI < 5 no apnea; 5 ≤ AHI < 15 mild apnea; 15 ≤ AHI < 30 moderate apnea; AHI ≥30 severe apnea). Bland-Altman plots were used for analysis, and 2 × 2 decision statistics were calculated for several cut-off values of the AHI. Data were shown as bias with limits of agreement (bias±1.96 standard deviations)., Results: Nineteen subjects were studied: nine (47%) were diagnosed with obstructive, seven (37%) with central sleep apnea, and three (16%) with no sleep apnea by overnight PSG. Perioperative PG bias was 12 (-37; 61) for AHI; 6 (-25; 37) for obstructive apnea; 0 (-4; 4) for central apnea, and 6 (-31; 43) for hypopnea. For the detection of OSA, a PG cut-off value of AHI 5 yielded 89% sensitivity and 60% specificity, AHI 15 yielded 86% sensitivity and 67% specificity, and AHI 30 yielded 100% sensitivity and 71% specificity., Conclusion: Wide limits of agreement preclude perioperative PG to be used as a diagnostic method; however, it may be useful to screen sedated surgical patients for OSA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Increased CO2 chemosensitivity and augmented exercise ventilation are characteristic of patients with heart failure (HF) with central sleep apnea (CSA). The aim of this study was to test the hypothesis that decreased end-tidal CO2 by cardiopulmonary exercise testing predicts CSA in patients with HF., Methods: Consecutive ambulatory patients with New York Heart Association II to III HF were prospectively evaluated by CO2 chemosensitivity by rebreathe, cardiopulmonary exercise testing, and polysomnography (PSG). Subjects were classified as having either CSA (n = 20) or no sleep apnea (n = 13) by PSG; a central apnea-hypopnea index (AHI) ≥ 5 was used to define CSA. Subgroups were compared by t test or Mann-Whitney test and data summarized as mean ± SD. P < .05 was considered significant., Results: At rest, subjects with CSA had higher central CO2 chemosensitivity (Δminute ventilation [V.e]/Δpartial pressure of end-tidal CO2 [Petco2], 2.3 ± 1.0 L/min/mm Hg vs 1.6 ± 0.4 L/min/mm Hg, P = .02) and V.e (15 ± 7 L/min vs 10 ± 3 L/min, P = .02) and lower Petco2 (31 ± 4 mm Hg vs 35 ± 4 mm Hg, P < .01) than control subjects. At peak exercise, the ventilatory equivalents per expired CO2 (V.e/V.co2) was higher (43 ± 9 vs 33 ± 6, P < .01) and Petco2 lower (29 ± 6 mm Hg vs 36 ± 5 mm Hg, P < .01) in subjects with CSA. In addition, CO2 chemosensitivity, peak exercise V.e/V.co2, and Petco2 were independently correlated with CSA severity as quantified by the AHI (P < .05). Peak exercise Petco2 was most strongly associated with CSA (OR, 1.29; 95% CI, 1.08-1.54; P = .01; area under the curve, 0.88)., Conclusions: In patients with HF and CSA, ventilatory drive is increased while awake at rest and during exercise and associated with heightened CO2 chemosensitivity and decreased arterial CO2 set point.

Background: Heart failure (HF) is characterized by heightened sensitivities of the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive manifested as increased minute ventilation per volume of expired CO2 (VE/VCO2). The aims of this study were to evaluate the effects of cardiac resynchronization therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2 setpoint., Methods and Results: Consecutive HF patients (n = 35) who underwent clinically indicated CRT were investigated by means of cardiopulmonary exercise testing and CO2 chemosensitivity evaluation with the use of a rebreathe method before and 4-6 months after CRT. Pre- and post-CRT measures were compared with the use of either paired t test or Wilcoxon test. Decreased peak VE/VCO2 (44 ± 10 vs 40 ± 8; P < .01), CO2 chemosensitivity (2.2 ± 1.1 vs 1.7 ± 0.8 L min(-1) mm Hg(-1); P = .04), and increased peak end-tidal CO2 (29 ± 5 vs 31 ± 5 mm Hg; P < .01) were also observed after CRT. Multivariate analysis adjusted for age and sex showed the decrease of peak VE/VCO2 from before to after CRT to be most strongly associated with the increase of peak end-tidal CO2 (β = -0.84; F = 21.5; P < .0001)., Conclusions: Decrease of VE/VCO2 after CRT is associated with decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint, which is consistent with decreased activation of both the CO2 chemoreflex and the ergoreflex., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Leptin-deficient animals hyperventilate. Leptin expression by adipocytes is attenuated by atrial natriuretic peptide (ANP). Increased circulating natriuretic peptides (NPs) are associated with an increased risk of central sleep apnea (CSA). This study tested whether serum leptin concentration is inversely correlated to NP concentration and decreased in patients with heart failure (HF) and CSA., Methods: Subjects with HF (N = 29) were studied by measuring leptin, NPs, CO2 chemosensitivity (Δminute ventilation [V.e]/Δpartial pressure of end-tidal CO2 [Petco2]), and ventilatory efficiency (V.e/CO2 output [V.co2]) and were classified as CSA or no sleep-disordered breathing by polysomnography. CSA was defined as a central apnea-hypopnea index ≥ 15. The Student t test, Mann-Whitney U test, and logistic regression were used for analysis, and data were summarized as mean ± SD; P &lt; .05 was considered significant., Results: Subjects with CSA had higher ANP and brain natriuretic peptide (BNP) concentrations (P &lt; .05), ΔV.e/ΔPetco2 (2.39 ± 1.03 L/min/mm Hg vs 1.54 ± 0.35 L/min/mm Hg, P = .01), and V.e/V.co2 (43 ± 9 vs 34 ± 7, P &lt; .01) and lower leptin concentrations (8 ± 10.7 ng/mL vs 17.1 ± 8.8 ng/mL, P &lt; .01). Logistic regression analysis (adjusted for age, sex, and BMI) demonstrated leptin (OR = 0.07; 95% CI, 0.01-0.71; P = .04) and BNP (OR = 4.45; 95% CI, 1.1-17.9; P = .05) to be independently associated with CSA., Conclusions: In patients with HF and CSA, leptin concentration is low and is inversely related to NP concentration. Counterregulatory interactions of leptin and NP may be important in ventilatory control in HF.

Background: Increased serum leptin concentration has been linked to increased ventilation in patients with mild heart failure (HF). However, in animal models the absence of leptin has also been associated with increased ventilation. This study evaluated the relationship of circulating leptin concentration with exercise ventilation in HF patients., Methods and Results: Fifty-eight consecutive ambulatory HF patients were stratified by quintiles of leptin concentration, with a lowest quintile of mean leptin concentration of 1.8 ± 8.9 ng/mL and a highest of 33.3 ± 30.3 ng/mL. Peak exercise ventilatory efficiency (VE/VCO2) was significantly elevated in the lowest (46 ± 6 vs 34 ± 4; P < .01) as well as in the highest (38 ± 8 vs 34 ± 4; P < .05) leptin concentration quintiles compared with the reference middle quintile. Multiple regression analysis adjusted for confounders such as age, sex, and body mass index showed leptin concentration to be independently inversely correlated to VE/VCO2 in the low-to-normal quintiles (β = -0.64; P < .01), positively in the normal-to-high quintiles (β = 0.52; P = .02), and positively correlated to PETCO2 in the low-to-normal quintiles (β = 0.59; P = .01) and inversely in the normal-to-high quintiles (β = -0.53; P = .02)., Conclusions: In HF patients, both high and low leptin concentrations are associated with increased VE/VCO2 and decreased PETCO2 with a nonlinear U-shaped relationship, suggesting that either leptin deficiency or leptin resistance may modulate ventilatory control in HF patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pulmonary congestion due to heart failure causes abnormal lung function. Cardiac resynchronization therapy (CRT) is a proven effective treatment for heart failure. The aim of this study was to test the hypothesis that CRT promotes increased lung volumes, bronchial conductance, and gas diffusion. Forty-four consecutive patients with heart failure were prospectively investigated before and after CRT. Spirometry, gas diffusion (diffusing capacity for carbon monoxide), cardiopulmonary exercise testing, New York Heart Association class, brain natriuretic peptide, the left ventricular ejection fraction, left atrial volume, and right ventricular systolic pressure were assessed before and 4 to 6 months after CRT. Pre- and post-CRT measures were compared using either paired Student's t tests or Wilcoxon's matched-pair test; p values <0.05 were considered significant. Improved New York Heart Association class, left ventricular ejection fraction, left atrial volume, right ventricular systolic pressure, and brain natriuretic peptide were observed after CRT (p <0.05 for all). Spirometry after CRT demonstrated increased percentage predicted total lung capacity (90 ± 17% vs 96 ± 15%, p <0.01) and percentage predicted forced vital capacity (80 ± 19% vs 90 ± 19%, p <0.01). Increased percentage predicted total lung capacity was significantly correlated with increased peak exercise end-tidal carbon dioxide (r = 0.43, p = 0.05). Increased percentage predicted forced vital capacity was significantly correlated with decreased right ventricular systolic pressure (r = -0.30, p = 0.05), body mass index (r = -0.35, p = 0.02) and creatinine (r = -0.49, p = 0.02), consistent with an association of improved bronchial conductance and decreased congestion. Diffusing capacity for carbon monoxide did not significantly change. In conclusion, increased lung volumes and bronchial conductance due to decreased pulmonary congestion and increased intrathoracic space contribute to an improved breathing pattern and decreased hyperventilation after CRT. Persistent alveolar-capillary membrane remodeling may account for unchanged diffusing capacity for carbon monoxide., (Copyright © 2013 Elsevier Inc. All rights reserved.)