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      Oxygen Uptake Efficiency Slope Predicts Poor Outcome in Patients With Idiopathic Pulmonary Arterial Hypertension

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          Abstract

          Background

          Few published studies have evaluated the power of the oxygen uptake efficiency slope ( OUES) to predict outcomes in patients with idiopathic pulmonary arterial hypertension ( IPAH), who typically die of right‐sided heart failure. Our study sought to evaluate the power of OUES to predict clinical worsening and mortality in patients with IPAH.

          Methods and Results

          Patients with newly diagnosed IPAH who underwent symptom‐limited cardiopulmonary exercise testing from November 11, 2010, to June 25, 2015, in our hospital were prospectively enrolled and followed for up to 66 months. Clinical worsening and mortality were recorded. A total of 210 patients with IPAH (159 women; mean age, 32±10 years) were studied with a median follow‐up of 41 months. Thirty‐one patients died, 1 patient underwent lung transplantation, and 85 patients presented with clinical worsening. The univariate analysis revealed that OUES, OUESI ( OUESI= OUES/body surface area), peak oxygen uptake ( V ˙ O 2 ), peak V ˙ O 2 / kg , ventilation ( V ˙ E )/carbon dioxide output ( V ˙ CO 2 ) slope, peak systolic blood pressure, heart rate recovery, pulmonary vascular resistance, cardiac index, N‐terminal prohormone brain natriuretic peptide, and World Health Organization functional class were all predictive of clinical worsening and mortality (all P<0.05). Multivariate analysis demonstrated that OUESI and cardiac index were independently predictive of clinical worsening, and OUESI and N‐terminal prohormone brain natriuretic peptide were independently predictive of mortality. Patients with OUESI ≤0.52 m −2 had a worse 5‐year survival rate than patients with OUESI >0.52 m −2 (41.9% versus 89.8%, P<0.0001).

          Conclusions

          The OUES, a submaximal parameter obtained from cardiopulmonary exercise testing, provides prognostic information for predicting clinical worsening and mortality in patients with IPAH.

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          Most cited references24

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          Predicted values for clinical exercise testing.

          Following thorough evaluation at rest, 265 of 400 current or ex-shipyard workers rode a cycle ergometer with equal work increments each minute to exhaustion while continuous multiple noninvasive cardiorespiratory measures and intermittent intra-arterial blood pressure and blood gas measures were made. Seventy-seven men, with a mean age of 54, including some who were smokers, obese, or hypertensive, were judged to have normal cardiorespiratory systems based on history, physical, electrocardiogram during rest and exercise, chest X-ray, pulmonary function tests, and exercise performance. Their responses to exercise are given. It was unusual to find at maximal exercise a breathing reserve less than 11 L/min, arterial PO2 less than 80 mm Hg, alveolar-arterial PO2 difference greater than 38 mm Hg, arterial-end tidal PCO2 difference greater than 1 mm Hg, respiratory frequency greater than 60, or a dead space/tidal volume ratio greater than 0.28. The normal anaerobic threshold/maximal O2 uptake ratio exceeded 40%. With maximal exercise, the intra-arterial systolic and diastolic pressures rose an average of 68 and 13 mm Hg, respectively. For predicting maximal oxygen uptake and oxygen pulse in an overweight man, we find it preferable to use age and height rather than age and weight.
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            Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise.

            We investigated the usefulness of a new variable, oxygen uptake efficiency slope (OUES), as a submaximal measure of cardiorespiratory functional reserve. The OUES is derived from the relation between oxygen uptake (Vo2 [ml/min]) and minute ventilation (VE [liters/min]) during incremental exercise and is determined by VO2 = a log VE + b, where a = OUES, which shows the effectiveness of Vo2. Maximal oxygen uptake (VO2max) is effort dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. Exercise tests, following a standard Bruce protocol, were performed on a treadmill by 108 patients with heart disease and 36 normal volunteers. Expired gas was continuously analyzed. The OUES was calculated from data of the first 75%, 90% and 100% of exercise duration. We also determined the following submaximal variables: the ventilatory anaerobic threshold (VAT), the slope of the regression line of the minute ventilation-carbon dioxide production relation (VE-VCO2 slope) and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relation of OUES and other submaximal variables against VO2max and examined the effects of submaximal exercise on OUES. The correlation coefficient of the logarithmic curve-fitting model was 0.978 +/- 0.016 (mean +/- SD). The OUES and VO2max had a significant correlation (r = 0.941, p < 0.0001). The correlation between VO2max and OUES was stronger than that between VO2max and VAT, the VE-VCO2 slope or EMOC. The OUES values for 100% and 90% of exercise were not different from each other (at an alpha value of 0.05 and treatment effect of 170, the power of the test [1-beta] was 0.90); OUES for 75% of exercise was slightly lower (3.5%). Our results suggest that OUES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve that is related both to pulmonary dead space and to metabolic acidosis.
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              Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise.

              We sought to evaluate, in adults, the efficacy of the Oxygen Uptake Efficiency Slope (OUES), an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort. Maximal oxygen uptake (VO2,max), the most reliable measure of exercise capacity, is seldom attained in standard exercise testing. The OUES, which relates oxygen uptake to total ventilation during exercise, was proposed by Baba and coworkers (7) in a study of pediatric cardiac patients. They felt this submaximal index of cardiopulmonary reserve might be more practical than VO2max and more appropriate than the commonly used peak oxygen consumption (VO2 peak). Treadmill exercise tests with simultaneous respiratory gas measurement were performed in 998 older subjects free of clinically recognized cardiovascular disease and 12 male patients with congestive heart failure. During incremental exercise, oxygen uptake was plotted against the logarithm of total ventilation, and the OUES was determined. The OUES, when calculated only from the first 75% of the exercise test, differed by 1.9% from the OUES calculated from 100% of exercise time in subjects with a peak respiratory exchange rate > or =1.10. On serial tests the OUES was less variable than exercise duration or VO2 peak. It correlated strongly with VO2max, with forced expiratory volume in 1 s and negatively with a history of current smoking. The OUES declined linearly with age in both women and men. A small sample of patients with congestive heart failure had OUES values much lower than those of older subjects without cardiovascular disease. The OUES is an objective, reproducible measure of cardiopulmonary reserve that does not require a maximal exercise effort. It integrates cardiovascular, musculoskeletal and respiratory function into a single index that is largely influenced by pulmonary dead space ventilation and exercise-induced lactic acidosis.
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                Author and article information

                Contributors
                zhihongliufuwai@163.com
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                30 June 2017
                July 2017
                : 6
                : 7 ( doiID: 10.1002/jah3.2017.6.issue-7 )
                : e005037
                Affiliations
                [ 1 ] Center for Pulmonary Vascular Diseases Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
                Author notes
                [*] [* ] Correspondence to: Zhihong Liu, PhD, Center for Pulmonary Vascular Diseases, Fuwai Hospital, 167 BeiLiShi Road, Xicheng District, Beijing 100037, China. E‐mail: zhihongliufuwai@ 123456163.com
                Article
                JAH32315
                10.1161/JAHA.116.005037
                5586266
                28666992
                f8b4c147-ad92-4b5d-936a-e8ee926c493c
                © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 09 November 2016
                : 05 May 2017
                Page count
                Figures: 5, Tables: 3, Pages: 9, Words: 6768
                Funding
                Funded by: Central Public Interest Scientific Institution Basal Research Fund
                Award ID: 2010F11
                Categories
                Original Research
                Original Research
                Hypertension
                Custom metadata
                2.0
                jah32315
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:25.07.2017

                Cardiovascular Medicine
                cardiopulmonary exercise testing,idiopathic pulmonary arterial hypertension,oxygen uptake efficiency slope,pulmonary hypertension

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