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Original Research |

Exhaled Acetone as a New Biomarker of Heart Failure SeverityExhaled Acetone and Heart Failure FREE TO VIEW

Fabiana G. Marcondes-Braga, MD, PhD; Ivano G. R. Gutz, PhD; Guilherme L. Batista, MSc; Paulo H. N. Saldiva, MD, PhD; Silvia M. Ayub-Ferreira, MD, PhD; Victor S. Issa, MD, PhD; Sandrigo Mangini, MD; Edimar A Bocchi, MD, PhD; Fernando Bacal, MD, PhD
Author and Funding Information

From the Laboratory of Heart Failure (Drs Marcondes-Braga, Ayub-Ferreira, Issa, Mangini, Bocchi, and Bacal), Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; Chemistry Institute (Dr Gutz and Mr Batista), University of São Paulo; and Laboratory of Experimental Air Pollution (Dr Saldiva), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.

Correspondence to: Fabiana G. Marcondes-Braga, MD, PhD, Av Dr Eneas de Carvalho Aguiar, 44 1° andar bloco 1, Laboratório de Insuficiência Cardíaca, Cerqueira Cesar, São Paulo CEP 05403-000, Brazil; e-mail: fgmarcondes@yahoo.com.br


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This work was supported by a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo [FAPESP grant number 08/06620-2]. Fellowships from Conselho Nacional do Desenvolvimento Científico e Tecnológico are acknowledged by Dr Gutz and Mr Batista.


Chest. 2012;142(2):457-466. doi:10.1378/chest.11-2892
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Background:  Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity.

Methods:  Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded.

Results:  The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001).

Conclusions:  EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity.

Figures in this Article

Heart failure (HF) is a condition associated with poor prognosis1 and frequent hospital admissions.2 In this context, multiple biomarkers of severity and prognosis of HF have emerged recently, including B-type natriuretic peptide (BNP),3 N-terminal proBNP,4 neutrophil gelatinase-associated lipocalin,5 soluble ST2,6 troponin,7 midregional proadrenomedullin,8 copeptin,9 chromogranin A,10 and S100B protein.11 The usefulness of the aforementioned biomarkers of HF, used independently, has not been fully established.12

BNP is a well-accepted marker for HF diagnosis.13 Although its accuracy in the diagnosis of chronic HF and acute decompensated heart failure (ADHF) has been extensively evaluated and specific cutoffs established, BNP testing is limited by caveats that may make its interpretation challenging, including intermediate gray zone values and nuances in interpreting levels in the settings of renal dysfunction, obesity, and advanced age.14,15

Exhaled breath has been considered a suitable tool to evaluate diseases of the respiratory system16 and those that involve metabolic changes, such as diabetes.17 Many substances have been identified as biomarkers of these diseases, such as ethane and 1-pentane, isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide).18 However, there is little research on exhaled breath of patients with cardiac diseases and, more specifically, with HF. In a previous study, it was shown that patients undergoing cardiac surgery exhale acetone (propanone) soon after the end of extracorporeal circulation probably because of oxidative stress.19 In another study, Kupari et al20 observed higher concentrations of acetone in patients with HF compared with healthy individuals; however, there were few patients enrolled, and the study did not establish whether exhaled breath could help in the diagnosis of HF and prediction of HF severity.

Based on these findings and on the fact that in a pilot study we identified acetone in the exhaled breath of patients with HF, we investigated a primary end point of exhaled acetone as a valuable tool for the diagnosis of chronic HF and ADHF and as a biomarker of HF severity by analyzing the correlation between exhaled breath acetone (EBA) and New York Heart Association (NYHA) classification (F. G. Marcondes-Braga, MD, PhD; I. G. R. Gutz, PhD; G. L. Batista, MSc; et al, unpublished data, 2008). As a secondary end point, we investigated the correlation between EBA and plasma BNP levels.

Study Population

The study was approved by the Institutional Ethics Committee (1045/07). Patients were enrolled from May 2009 to September 2010. To be eligible for the study, patients had to have an ejection fraction of no more than 40%. The diagnosis of HF was established according to two major or one major and two minor Framingham criteria.21 Patients with diabetes, chronic renal failure, or chronic hepatic failure; pregnant women; and patients on long-term corticosteroids were excluded because these comorbidities and drugs interfere directly with the ketoacid metabolism. Patients not using β-blockers were excluded because these drugs could also change ketoacid metabolism and are essential to the treatment of HF. All eligible patients were evaluated as soon as they were admitted to the ED (ADHF group) or arrived at the hospital (chronic HF group). The clinical diagnosis of HF was adjudicated by a cardiologist who was blind to the results of the exhaled breath collection. Twenty sex- and age-matched healthy subjects were also enrolled (control group).

Once written informed consent was obtained, eligible patients received a standardized meal consisting of a cup of tea and three cookies and underwent blood collection to determine BNP level, electrolyte levels, renal function, liver function, CBC count, and venous lactate level and urinalysis followed by breath collection with a portable, noninvasive device designed to meet the study purpose. Exhaled breath was collected before starting treatment and 60 min after the meal to avoid fasting-induced ketone body increase.

Study Design

Figure 1 depicts the study design. First, patients with HF (HF group) were compared with healthy subjects (control group). Second, patients with HF were grouped according to clinical criteria in a chronic HF group (defined by being stable for at least 3 months) and an ADHF group (comprising patients with pulmonary/systemic congestive symptoms or low output signs consecutively admitted to the ED.21,22

Collection and Analysis of Exhaled Breath

A simple, portable breath collector was developed for this study (e-Figure 1). During the exhaled breath collection, the participant blew through a disposable inlet tube to a glass bubbler (impinger), which contained 5.0 mL of icy distilled water and was immersed in an ice water bath. The generation of small bubbles in cold water by a diffuser increased gas-water contact and enhanced the efficiency of soluble compounds extraction. A short hose of an otherwise sealed empty plastic bag was connected to the impinger output duct, enabling the collection of a fixed volume of breath (7.6 L) from each patient. All patients were asked to breathe naturally until the bag was completely filled with 7.6 L of exhaled air. The retention efficiency of exhaled acetone determined for this collector (using 7.6 L of exhaled air bubbled in 5 mL of ice-cooled water) is 78%.23 This factor and acetone losses of 24% during the freezing, storage, and defrosting procedure, constant for 1 to 60 days,23 was taken into account in the chemical analysis. After collection, the liquid phase was transferred from the impinger to a capped vial and stored in a freezer at −112°F (−80°C) until acetone analysis could be done. The identification of acetone in defrosted aqueous extracts was done by gas chromatography-mass spectrometry, and quantitative determination was done by spectrophotometry after reaction with salicylaldehyde.24

Statistical Analysis

Data were analyzed using SPSS for Windows, version 13.0 (SPSS Inc) statistical software. The categorical variables are shown as absolute (n) and relative frequency (%), and the groups were compared by Pearson χ2 test. To test normality, we used the Kolmogorov-Smirnov test. Parametric data are presented as mean ± SD, and independent groups were compared by Student t test. Nonparametric data were shown as median and interquartile range. Independent groups were compared by Mann-Whitney test. Spearman correlation coefficient was used to evaluate the correlations among continuous variables. Kruskal-Wallis test and Dunn test were used to analyze the continuous variables according to NYHA classification. We constructed receiver operating characteristic (ROC) curves to assess sensitivity, specificity, and accuracy of the exhaled breath diagnostic method and compared with those of BNP measurements. The area under the curve (AUC) indicates the diagnostic accuracy of the test, for which AUC ≥ 0.8 is considered good accuracy. Logistic regression was used to analyze the exhaled breath capacity for predicting HF diagnosis. Univariable analysis was done to assess the influence of variables on EBA, and P < .10 was required to enter a variable into the stepwise multivariable linear regression analysis.

A total of 235 patients with left ventricular systolic dysfunction were enrolled, of whom 183 were consecutively admitted through the ED of the Heart Institute (InCor) because of ADHF and 52 patients with stable chronic HF were referred for a cardiopulmonary test. Eighty-nine patients fulfilled the study criteria (chronic HF group, 30 patients; ADHF group, 59 patients). Exhaled breath analysis identified acetone (propanone, CH3-CO-CH3) in high concentration in patients with HF, confirming the results from our pilot study and those of Kupari et al.20

Exhaled Acetone and HF Diagnosis

Table 1 shows clinical data and comparisons between the control (n = 20) and HF (n = 89) groups. The median (interquartile range) concentration of EBA was 0.39 μg/L (0.30-0.79 μg/L) in the control group and 3.70 μg/L (1.69-10.45 μg/L) in the HF group (P < .001). The median concentration of BNP was 9.50 pg/mL (4.50-13.50 pg/mL) in the control group and 997 pg/mL (329-2,059 pg/mL) in the HF group (P < .001) (Figs 2A, 2B). The ROC curve was used to differentiate patients with HF from healthy subjects. The AUC was 0.94 (95% CI, 0.91-0.99; P < .001). The EBA cutoff value of 1.16 μg/L had a sensitivity of 83%, specificity of 100%, and accuracy of 86% for differentiating patients with HF from healthy subjects. For the diagnosis of HF, the EBA cutoff of 1.16 μg/L was as accurate as a BNP level of 42 pg/mL (AUC, 0.97; 95% CI, 0.94-1.00; P < .001) (Fig 3A).

By using logistic regression models, we determined that EBA (acetone value > 1.16 μg/L) predicted the HF diagnosis (patients with HF vs control subjects) in 86.2% of the cases. The same procedures using BNP level (> 42 pg/mL) identified 93.6% of the cases. When acetone and BNP were considered simultaneously in a logistic regression model, it was possible to predict HF diagnosis in 95.4% of the cases.

EBA and ADHF Diagnosis

Table 2 depicts clinical data and a comparison between the chronic HF (n = 30) and the ADHF (n = 59) groups. The median (interquartile range) concentration of EBA was 1.22 μg/L (0.68-2.19 μg/L) in the chronic HF group and 7.80 μg/L (3.60-15.20 μg/L) in the ADHF group (P < .001). The median concentration of BNP was 224 pg/mL (45-394 pg/mL) in the chronic HF group and 1,527 pg/mL (905-2,475 pg/mL) in the ADHF group (P < .001) (Figs 2C, 2D). ROC curve analysis was used to differentiate patients with ADHF from those with chronic HF. The AUC was 0.93 (95% CI, 0.88-0.98; P < .001). The acetone cutoff value of 2.50 μg/L had a sensitivity of 86%, specificity of 80%, and accuracy of 84% for the diagnosis of ADHF. For the diagnosis of ADHF in the study population, an EBA cutoff of 2.50 μg/L was as accurate as a BNP cutoff of 424 pg/mL (AUC, 0.94; 95% CI, 0.88-0.99; P < .001) (Fig 3B).

By using logistic regression models, we determined that EBA (acetone > 2.5 μg/L) predicted the clinical profile of HF (chronic HF vs ADHF) in 84.3% of the cases. The same procedures using BNP levels (> 424 pg/mL) identified 92% of the cases. The same classification rate was observed when EBA and BNP levels were considered simultaneously in the logistic regression model.

EBA and NYHA Classification

To analyze the relationship of EBA to HF severity, we evaluated the EBA concentration according to the NYHA classification. The median (interquartile range) concentration of EBA was 0.60 μg/L (0.50-0.70 μg/L) among patients in NYHA functional class I (n = 2); 1.50 μg/L (0.80-2.20 μg/L) among those in class II (n = 18); 5.60 μg/L (1.70-10.1 μg/L) among those in class III (n = 39), and 8.10 μg/L (3.60-17.10 μg/L) among those in class IV (n = 30). As symptom severity rose, a significant increase in median EBA levels was observed (P < .001). Figure 4 shows the significant relationship between NYHA symptom severity and EBA levels.

Univariable and Multivariable Analyses

Table 3 shows the variables univariably related to high levels of exhaled acetone. Bilirubin, respiratory rate, creatinine level, hepatojugular reflux, syncope, narrow proportional pulse pressure, and right ventricle dysfunction were independently associated with high levels of EBA (Table 3). None of the medications tested was independently associated to acetone. Because multiple linear regression showed low linearity for continuous (adjusted r2 = 0.48) and categorical (adjusted r2 = 0.43) variables, these variables could not be considered predictors of EBA levels.

EBA and BNP Levels

We also analyzed the correlation between EBA and BNP. Figure 5 depicts the significant positive correlation between EBA and BNP levels (r = 0.772, P < .001).

The results confirmed that acetone is increased in exhaled breath of patients with HF, as previously pointed out by Kupari et al.20 But more interestingly and importantly, the presented study revealed, for the first time in our knowledge, that EBA is a good biomarker of HF diagnosis and that it is related to HF severity. EBA was helpful in distinguishing ADHF from chronic HF (sensitivity, 86%; accuracy, 84%), exhibiting the same behavior as BNP in this respect, and presented a positive correlation with BNP level. In addition, and perhaps more relevant to clinical practice, EBA levels differed significantly as a function of severity of HF (NYHA classification). Furthermore, we observed that high levels of EBA were associated with variables related to right ventricle involvement probably because of a high frequency of Chagas disease in the present population and association with variables that reflect greater severity of the disease. These findings strongly suggest that EBA may play an important clinical role in the management of patients with HF mainly because it seems to reflect physiologic changes of advanced HF. The results are in line with the concept of the need of biomarkers of cardiovascular diseases.25

Previously, clinical studies have shown that breath acetone is indicative of systemic ketosis26; however, possible mechanisms that lead to an augmented concentration of EBA in patients with HF remain unclear. It is well established that patients with HF have increased plasma catecholamine levels. High levels of norepinephrine stimulate lipolysis and increase plasma free fatty acid (FFA) concentrations presumably because of greater β-adrenergic stimulation.27 During stressful situations, such as starvation28 and advanced HF,29 high levels of FFAs result in an increase of acetyl-coenzyme A levels in mitochondria, which lead to a series of condensation reactions that produce the following three types of ketone bodies: acetoacetate, β-hydroxybutyrate, and acetone. Of these three molecules, acetoacetate and β-hydroxybutyrate are metabolically active and can be detected in the blood, but the volatility of acetone allows detection of ketosis by exhaled breath. Although the liver possesses the necessary enzymes for ketone body production, it does not produce the necessary enzymes to metabolize these compounds. As a result, ketone bodies accumulate in the blood to provide a source of energy to tissues, such as brain, heart, muscle, and kidney, during conditions of glucose scarcity. In addition, it was shown in vitro that ketone bodies regulate cardiac glucose uptake through inhibition of adenosine monophosphate-activated protein kinase/p38 MAPK signaling pathway and reactive oxygen species overproduction, which could contribute to a change in myocardial metabolism in advanced HF.30 In fact, FFA and glucose are the main substrates used by myocardial cells to produce energy (adenosine triphosphate) by β-oxidation and glycolysis. The contribution from each of these substrates can change depending on the stage of the disease. In advanced HF, fatty acid use decreases substantially and insulin resistance develops in myocardium, and most studies have shown a decline in glucose use.31 In this stage of the disease, there is some clinical evidence32,33 that high concentrations of ketone bodies could impair myocardial glucose and FFA use and could contribute to myocardial damage.34 In this context, elevated EBA seems to be a marker of systemic disease severity and to play a role in promoting cardiac damage. In short, the present study shows that EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP level but also is a new biomarker of HF severity.

The main limitation of the present study is the small sample size; nonetheless, available results on the potential of EBA as a new biomarker of HF severity are relevant and might inspire prompt confirmatory studies by other groups. We consider that this new method can be easily reproduced. However, because we report on a new technology, our methods have not been extensively tested in other conditions. Furthermore, the exclusion of patients with diabetes and renal failure to avoid potential bias during the establishment of the new method is a shortcoming to be dealt with in further research on the possibility of wider application of the method to patients with HF with other chronic conditions.

Table Graphic Jump Location
Table 1 —Baseline Characteristics of Patients in Control and HF Groups

Data are presented as median (interquartile range) or No. (%). HF = heart failure; LVDD = left ventricle diastolic diameter; LVEF = left ventricular ejection fraction; O2 = oxygen.

Table Graphic Jump Location
Table 2 —Baseline Characteristics of Patients in Chronic HF and ADHF Groups

Data are presented as median (interquartile range) or No. (%). P values are for the difference between the chronic HF and ADHF groups. ACEI = angiotensin-converting enzyme inhibitor; ADHF = acute decompensated heart failure; ARB = angiotensin II receptor blocker; γ-GT = γ-glutamil transferase; GOT = glutamic oxaloacetic transaminase; GPT = glutamic pyruvic transaminase; NYHA = New York Heart Association. See Table 1 legend for expansion of other abbreviations.

a 

Hemodynamic profile: A = hot and dry; B = hot and wet; C = cold and wet.

Table Graphic Jump Location
Table 3 —Univariable and Multiple Linear Regression Analysis

BNP = B-type natriuretic atrial peptide. See Table 1 and 2 legends for expansion of other abbreviations.

Figure Jump LinkFigure 1. Study design. ADHF = acute decompensated heart failure; CHF = chronic heart failure; CPT = cardiopulmonary test; CRF = chronic renal failure; EF = ejection fraction; GC-MS = gas chromatography-mass spectrometry; HF = heart failure; w/o = without.Grahic Jump Location
Figure Jump LinkFigure 2. EBA and BNP levels in the diagnosis of CHF and ADHF. A, Median EBA concentration for CHF group. B, Median BNP concentration for CHF group. EBA and BNP concentrations were significantly higher in HF group than in the control group. C, Median EBA concentration for the ADHF group. D, Median BNP concentration for the ADHF group. EBA and BNP concentrations were significantly higher in the ADHF group than in the CHF group. Boxes show interquartile ranges, and bars represent highest and lowest values.Grahic Jump Location
Figure Jump LinkFigure 3. Receiver operating characteristic (ROC) curves for the diagnosis of chronic HF and ADHF. A, ROC curves for EBA and BNP to diagnose HF. B, ROC curves for EBA and BNP to differentiate chronic HF from ADHF. AUC = area under the curve. See Figure 1 and 2 legends for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4. Median EBA concentration in patients with HF expressed as a function of NYHA symptom severity. Boxes show interquartile ranges, and bars represent highest and lowest values. NYHA = New York Heart Association. See Figure 1 and 2 legends for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 5. Correlation between EBA and BNP concentrations. See Figure 2 legend for expansion of abbreviations.Grahic Jump Location

Author contributions: Dr Marcondes-Braga had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Marcondes-Braga: contributed to all steps of the study including the development of the device, study design, data collection, chemical analysis, data analysis and interpretation, and writing and review of the manuscript.

Dr Gutz: contributed to the development of the device used in the study, chemical analysis (spectrophotometry), and review of the manuscript.

Mr Batista: contributed to the development of the device used in the study and chemical analysis (spectrophotometry).

Dr Saldiva: contributed to study design, data analysis, and review of the manuscript.

Dr Ayub-Ferreira: contributed to data analysis and review of the manuscript.

Dr Issa: contributed to data analysis and review of the manuscript.

Dr Mangini: contributed to data analysis and review of the manuscript.

Dr Bocchi: contributed to data analysis and review of the manuscript.

Dr Bacal: contributed to study design, data analysis and interpretation, writing and review of the manuscript.

Other contributions: We are grateful to the Central Analytical Facility of the Chemistry Institute for the gas chromatography-mass spectrometry analyses.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Bocchi has received in-kind benefits (travel and accommodations) and consultant fees from Merck & Co, Inc; has been a consultant to Laboratori Baldacci SPA and Les Laboratoires Servier; has received grant monies and in-kind benefits (travel, accommodations, consultant fees, money for patient enrollment, speaking activities) from Les Laboratoires Servier; and has received grant monies from AstraZeneca. Drs Marcondes-Braga, Gutz, Saldiva, Ayub-Ferreira, Issa, Mangini, and Bacal and Mr Batista have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Additional information: The e-Figure can be found in the “Supplemental Materials” area of the online article.

ADHF

acute decompensated heart failure

AUC

area under the curve

BNP

B-type natriuretic peptide

EBA

exhaled breath acetone

FFA

free fatty acid

HF

heart failure

NYHA

New York Heart Association

ROC

receiver operating characteristic

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Figures

Figure Jump LinkFigure 1. Study design. ADHF = acute decompensated heart failure; CHF = chronic heart failure; CPT = cardiopulmonary test; CRF = chronic renal failure; EF = ejection fraction; GC-MS = gas chromatography-mass spectrometry; HF = heart failure; w/o = without.Grahic Jump Location
Figure Jump LinkFigure 2. EBA and BNP levels in the diagnosis of CHF and ADHF. A, Median EBA concentration for CHF group. B, Median BNP concentration for CHF group. EBA and BNP concentrations were significantly higher in HF group than in the control group. C, Median EBA concentration for the ADHF group. D, Median BNP concentration for the ADHF group. EBA and BNP concentrations were significantly higher in the ADHF group than in the CHF group. Boxes show interquartile ranges, and bars represent highest and lowest values.Grahic Jump Location
Figure Jump LinkFigure 3. Receiver operating characteristic (ROC) curves for the diagnosis of chronic HF and ADHF. A, ROC curves for EBA and BNP to diagnose HF. B, ROC curves for EBA and BNP to differentiate chronic HF from ADHF. AUC = area under the curve. See Figure 1 and 2 legends for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4. Median EBA concentration in patients with HF expressed as a function of NYHA symptom severity. Boxes show interquartile ranges, and bars represent highest and lowest values. NYHA = New York Heart Association. See Figure 1 and 2 legends for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 5. Correlation between EBA and BNP concentrations. See Figure 2 legend for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Baseline Characteristics of Patients in Control and HF Groups

Data are presented as median (interquartile range) or No. (%). HF = heart failure; LVDD = left ventricle diastolic diameter; LVEF = left ventricular ejection fraction; O2 = oxygen.

Table Graphic Jump Location
Table 2 —Baseline Characteristics of Patients in Chronic HF and ADHF Groups

Data are presented as median (interquartile range) or No. (%). P values are for the difference between the chronic HF and ADHF groups. ACEI = angiotensin-converting enzyme inhibitor; ADHF = acute decompensated heart failure; ARB = angiotensin II receptor blocker; γ-GT = γ-glutamil transferase; GOT = glutamic oxaloacetic transaminase; GPT = glutamic pyruvic transaminase; NYHA = New York Heart Association. See Table 1 legend for expansion of other abbreviations.

a 

Hemodynamic profile: A = hot and dry; B = hot and wet; C = cold and wet.

Table Graphic Jump Location
Table 3 —Univariable and Multiple Linear Regression Analysis

BNP = B-type natriuretic atrial peptide. See Table 1 and 2 legends for expansion of other abbreviations.

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