Mitigation of Exercise Oscillatory Ventilation Score by Cardiac Resynchronization Therapy.

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 (CO2) 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 CO2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO2 production significantly decreased, and end-tidal CO2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO2 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 CO2 chemosensitivity.

Ventilatory Efficiency Identifies Patients Prone to Hypoxemia During One-Lung Ventilation.

OBJECTIVES: One-lung ventilation (OLV) may be complicated by hypoxemia. Ventilatory efficiency, defined as the ratio of minute ventilation to carbon dioxide output (VE/VCO2), is increased with ventilation/perfusion mismatch and pulmonary artery hypertension, both of which may be associated with hypoxemia. Hence, the authors hypothesized increased VE/VCO2 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 (FiO2) ≥0.7 to maintain arterial oxygen (O2) 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 VE/VCO2 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 VE/VCO2 slope (30 ± 5 v 27 ± 4; p = 0.04) with exercise and lower partial pressure of oxygen/FiO2 (129 ± 92 v 168 ± 88; p = 0.01), higher mean positive end-expiratory pressure (6.6 ± 1.5 v 5.6 ± 0.9 cmH2O; p = 0.02), and lower mean pulse oximetry O2 saturation/FiO2 index (127 ± 20 v 174 ± 17; p < 0.01) during OLV. Multiple regression showed VE/VCO2 to be independently associated with the mean pulse oximetry O2 saturation/FiO2 index (b = -0.28; F = 3.1; p = 0.05). CONCLUSIONS: An increased VE/VCO2 slope may predict hypoxemia development in patients who undergo OLV.

Assessment of Thoracic Blood Volume by Computerized Tomography in Patients With Heart Failure and Periodic Breathing.

BACKGROUND: Periodic breathing (PB) is often observed in patients with HF at rest, with sleep and during exercise. However, mechanisms underlying abnormal ventilatory control are not entirely established. METHODS: Eleven subjects with HF (10 males, age = 69 ± 12 y) and 12 age-matched control subjects (8 males, age = 65 ± 9 y) participated in the study. PB was defined as a peak in the 0.003-0.04 Hz frequency range of the flow signal during 6 minutes of awake resting breathing. Thoracic blood volumes (Vt, thorax; Vh, heart; Vp, pulmonary), mean transit times (MTTs), and extravascular lung water (EVLW) were quantified using computerized tomography. RESULTS: PB was observed in 7 subjects with HF and was associated with worse functional status. The HF PB-present group had thoracic blood volumes nearly double those of control and HF PB-absent subjects (volumes reported as mL/m2 body surface area, P values vs control: control = 813 ± 246, HF PB-absent = 822 ± 161 P = .981, HF PB-present = 1579 ± 548 P = .002). PB was associated with longer pulmonary MTT (control = 6.7 ± 1.2 s, HF PB-absent = 6.0 ± 0.8 s, HF PB-present = 8.4 ± 1.6 s; P = .033, HF PB-present vs HF PB-absent). EVLW was not elevated in the PB group. CONCLUSIONS: Subjects with HF and PB at rest have greater centralization of blood volume.

Low leptin concentration may identify heart failure patients with central sleep apnea.

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 Ë‚ 0.01) or no sleep apnea (8 ± 10.7 ng mL-1 versus 17.1 ± 8.4 ng mL-1 , P Ë‚ 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.

Influence of Thoracic Fluid Compartments on Pulmonary Congestion in Chronic Heart Failure.

INTRODUCTION: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. METHODS: Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. RESULTS: Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. CONCLUSIONS: Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows.

Modulation of ventilatory reflex control by cardiac resynchronization therapy.

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 (ß = -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.

The relationship between leptin and ventilatory control in heart failure.

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 (ß = -0.64; P < .01), positively in the normal-to-high quintiles (ß = 0.52; P = .02), and positively correlated to PETCO2 in the low-to-normal quintiles (ß = 0.59; P = .01) and inversely in the normal-to-high quintiles (ß = -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.

Hyperoxemia post thoracic surgery - Does it matter?

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 (PaO2)>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 PaO2 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.

The risk of post-operative pulmonary complications in lung resection candidates with normal forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide: a prospective multicentre study.

Introduction: According to the guidelines for preoperative assessment of lung resection candidates, patients with normal forced expiratory volume in 1 s (FEV1) 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 FEV1 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 FEV1 and D LCO. Of these, 17 patients (9%) developed PPC. Patients with PPC had significantly lower pressure of end-tidal carbon dioxide (P ETCO2 ) at rest (27.7 versus 29.9; p=0.033) and higher ventilatory efficiency (V'E/V'CO2 ) slope (31.1 versus 28; p=0.016) compared to those without PPC. Multivariate models showed association between resting P ETCO2 (OR 0.872; p=0.035) and V'E/V'CO2 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 ETCO2 adds incremental information for risk prediction of PPC in patients with normal FEV1 and D LCO. We propose resting P ETCO2 be an additional parameter to FEV1 and D LCO for preoperative risk stratification.

Prediction of Postoperative Complications: Ventilatory Efficiency and Rest End-tidal Carbon Dioxide.

BACKGROUND: Cardiopulmonary exercise testing parameters including ventilatory efficiency (VE/VCO2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. VE/VCO2 slope is closely related to the partial pressure of end-tidal carbon dioxide (PETCO2). We hypothesized PETCO2 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. PETCO2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and VE/VCO2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest PETCO2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and VE/VCO2 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 PETCO2: AUC = 0.79 (95% CI 0.74-0.85); VE/VCO2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48). CONCLUSIONS: PETCO2 at rest has similar prognostic utility as VE/VCO2 slope, suggesting rest PETCO2 may be used for postoperative pulmonary complications prediction in lung resection candidates.

Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications.

INTRODUCTION: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection. METHODS: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). RESULTS: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications. CONCLUSION: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

Left ventricle assist device pulsatility index at the time of implantation is associated with follow-up pulmonary hemodynamics.

HeartMate II left ventricular assist device controllers provide data including pulsatility index, reflecting the relationship between pump function and hemodynamics. We propose that a higher pulsatility index at hospital discharge following implant may be associated with less vascular congestion and improved clinical outcomes. A retrospective analysis of 40 patients (age 59.2 ± 10.3 years) supported with the HeartMate II devices was conducted. Data revealed moderate Pearson correlations between pulsatility index at discharge and right atrial pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure, respectively, post-surgery (median of 377 days), demonstrating a stronger relationship when analyzed for the EPC controller (n = 28) only (r = -.57, p < .01; r = -.38, p < .05; r = -.59, p < .01; r = -.47, p = .01 and r = -.53, p < .01, respectively). The pulsatility index derived from the EPC controller was associated with the significant risk of re-hospitalization within 1 and 2 years after the implantation of left ventricular assist device; hazard ratio = 0.557 with 95% confidence interval (0.315-0.983), p = .04 and hazard ratio = .579 (0.341-0.984), p = .04. A higher pulsatility index at discharge was associated with greater volume unloading, lower pulmonary pressures, and lower risk of all-cause re-hospitalizations within 1 and 2 years post-surgery. As such, pump-derived data may provide additional value in predicting left ventricular assist device hemodynamics.

Poor ventilatory efficiency during exercise may predict prolonged air leak after pulmonary lobectomy.

Poor ventilatory efficiency, defined as the increase in minute ventilation relative to carbon dioxide production during exercise (VE/VCO2 slope), may be associated with dynamic hyperinflation and thereby promote the development of prolonged air leak (PAL) after lung resection. Consecutive lung lobectomy candidates (n = 96) were recruited for this prospective two-centre study. All subjects underwent pulmonary function tests and cardiopulmonary exercise testing prior to surgery. PAL was defined as the presence of air leaks from the chest tube on the 5th postoperative day and developed in 28 (29%) subjects. Subjects with PAL were not different in terms of age, sex, American Society of Anesthesiologists class, type of surgery (thoracotomy/video-assisted thoracoscopic surgery) and site of surgery (right/left lung; upper/lower lobes). Subjects with PAL had more frequent pleural adhesions (50% vs 21%; P = 0.006) and steeper VE/VCO2 slope (35 ± 7 vs 30 ± 5; P = 0.001). Stepwise logistic regression showed that only the presence of pleural adhesions [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4-10.9; P = 0.008] and VE/VCO2 slope (OR 1.1, 95% CI 1.0-1.2; P = 0.003) were independently associated with PAL (AUC 0.74, 95% CI 0.62-0.86). We conclude that a high VE/VCO2 slope during exercise may be helpful in identifying patients at greater risk for the development of PAL after lung lobectomy. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03498352.

Obstructive sleep apnea and aldosterone.

BACKGROUND: Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects. METHODS AND RESULTS: Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9 pm), after 5 hrs of untreated OSA ( 2am) and in the morning after awakening (6 am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 +/- 9 vs 56.0 +/- 9 pg/mL; PRA: 0.99 +/- 0.15 vs. 1.15 +/- 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep. CONCLUSIONS: Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels.

Ventilatory expired gas at constant-rate low-intensity exercise predicts adverse events and is related to neurohormonal markers in patients with heart failure.

BACKGROUND: Ventilatory efficiency (VE/VCO(2) ratio) and the partial pressure of end-tidal carbon dioxide (P(ET)CO(2)), obtained during moderate to high levels of physical exertion demonstrate prognostic value in heart failure (HF). The present investigation assesses the clinical utility of these variables during low-intensity exercise. METHODS AND RESULTS: One hundred and thirty subjects diagnosed with HF underwent a 2-minute, constant-rate treadmill session at 2 miles per hour. Both the VE/VCO(2) ratio and P(ET)CO(2) were recorded during exercise (30-second average) and their change (Delta) from rest. B-type and atrial natriuretic peptide (BNP and ANP) were also determined. Only P(ET)CO(2) and DeltaP(ET)CO(2) emerged from the multivariate Cox regression. Receiver operating characteristic curve analysis revealed the prognostic classification schemes were significant with thresholds of < or >or=34 mm Hg (hazard ratio: 4.2, 95% CI: 2.2-8.0, P < .001) and < or >or=1 mm Hg (hazard ratio: 3.5, 95% CI: 1.9-6.6, P < .001) being optimal for P(ET)CO(2) and DeltaP(ET)CO(2), respectively. Moreover, subjects with a P(ET)CO(2)>or=34 mm Hg had a significantly lower BNP (214.1 +/- 431.9 vs. 1110.5 +/- 1854.0 pg/mL, P=.005) and ANP (108.2 +/- 103.6 vs. 246.2 +/- 200.4 pg/mL, P < .001). CONCLUSIONS: The results of this pilot study indicate ventilatory expired gas analysis during a short bout of low-intensity exercise may provide insight into prognosis and cardiac stability.

Pulmonary Limitations in Heart Failure.

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.

Cardiopulmonary exercise testing for identification of patients with hyperventilation syndrome.

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.

Central sleep apnea: implications for congestive heart failure.

Congestive heart failure (HF), an exceedingly common and costly disease, is frequently seen in association with central sleep apnea (CSA), which often manifests as a periodic breathing rhythm referred to as Cheyne-Stokes respiration. CSA has historically been considered to be a marker of heart disease, since improvement in cardiac status is often associated with the attenuation of CSA. However, this mirroring of HF and CSA may suggest bidirectional importance to their relationship. In fact, observational data suggest that CSA, associated with repetitive oxyhemoglobin desaturations and surges in sympathetic neural activity, may be of pathophysiologic significance in HF outcomes. In light of the disappointing results from the first large trial assessing therapy with continuous positive airway pressure in patients with CSA and HF, further large-scale interventional trials will be needed to assess the role, if any, of CSA treatment on the outcomes of patients with HF. This review will discuss epidemiologic, pathophysiologic, diagnostic, and therapeutic considerations of CSA in the setting of HF.

Exercise oscillatory ventilation: instability of breathing control associated with advanced heart failure.

BACKGROUND: Instability of breathing control due to heart failure (HF) manifests as exercise oscillatory ventilation (EOV). Prior descriptions of patients with EOV have not been controlled and have been limited to subjects with left ventricular ejection fraction (LVEF) of or= 0.40. Compared to control subjects, EOV subjects had increased left atrial dimension, mitral E-wave velocity, and right heart pressures as well as decreased exercise tidal volume response, functional capacity, rest and exercise end-tidal carbon dioxide, and increased ventilatory equivalent for carbon dioxide and dead space ventilation (all p < 0.05). Multivariate analysis demonstrated atrial fibrillation (odds ratio, 6.7; p = 0.006), digitalis therapy (odds ratio, 0.27; p = 0.02), New York Heart Association class (odds ratio, 3.5; p = 0.0006), rest end-tidal carbon dioxide (odds ratio, 0.87; p = 0.005), and peak heart rate (odds ratio, 0.98; p = 0.02) were independently associated with EOV. CONCLUSIONS: Patients with EOV have clinical characteristics and exercise ventilatory responses consistent with more advanced HF than patients with comparable LV systolic function; EOV may occur in HF patients with an LVEF of >or= 0.40.