Averaged decrease in SpO2 during six-minute walk test as a novel prognostic marker for elderly heart failure patients

Averaged decrease in SpO2 during six-minute walk test as a novel prognostic marker for elderly heart failure patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Averaged decrease in SpO2 during six-minute walk test as a novel prognostic marker for elderly heart failure patients Isamu Sunayama, Kyung-Duk Min, Yoshiyuki Orihara, Junichi Ono, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4173768/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Exercise capacity is pivotal in risk stratification in heart failure (HF) and the six-minute walk test (6MWT) is often employed to evaluate it, but estimation of the absolute risk in elderly patients through six-minute walk distance (6MWD) is difficult due to comorbidities resulting in wide variability among individuals, implicating unmet-needs for comprehensive index for exercise capacity in the elderly. Methods: During the 6MWT, 6MWD and exercise-induced changes in peripheral oxygen saturation (ΔSpO 2 -Ex) were measured. The associations between these parameters and cardiovascular outcomes, including HF rehospitalization and cardiovascular death within one year after discharge were assessed. Results: Fifty-five HF patients with age > 65 yeas were investigated. The mean 6MWD was 237.5 m, and the mean ΔSpO 2 -Ex was 5.8 %. Kaplan-Meier analysis revealed a significant correlation between larger ΔSpO 2 -Ex and adverse cardiovascular outcomes (HR 6.66, p<0.001) compared to 6MWD (HR 2.40, p=0.031). In multivariate analysis, ΔSpO 2 -Ex was an independent risk factor. The combination of short-6MWD and large-ΔSpO 2 -Ex identified patients with markedly high incidence rate of cardiovascular events. Conclusions: ΔSpO 2 -Ex could be an independent prognostic marker for HF patients, surpassing the predictive power of 6MWD, suggesting that the 6MWT can provide a novel prognostic assessment that reflects exercise capacity through ΔSpO 2 -Ex. Health sciences/Cardiology/Cardiovascular biology/Cardiovascular diseases/Heart failure Health sciences/Biomarkers/Prognostic markers Heart failure six-minute walk test peripheral oxygen saturation prognostic marker rehospitalization. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Heart failure (HF) is estimated to affect 38 million individuals worldwide. Despite notable advancements in treatment over the past couple of decades, HF continues to be a predominant cause of hospitalizations. Because a significant fraction of these hospitalizations is due to acute exacerbation of chronic HF 1, it is crucial to develop novel approaches to identify high-risk patients who need to be subjected to intense care to prevent rehospitalization. Exercise capacity is a widely accepted clinical index that is strongly correlated with the prognosis of patients with HF 2 . The index, including peak VO 2 and anabolic threshold, determined by the cardiopulmonary exercise test (CPET) remains the gold standard to evaluate the exercise capacity and prognosis of patients with HF. Meanwhile, because CPET requires substantial materials and resources, the six minute-walk test (6MWT) is frequently employed as a preferable alternative, as it is a non-invasive and cost-effective test that demonstrates daily activity energy expenditure 3,4 . The distance covered during this test, termed six-minute walk distance (6MWD), is a pivotal index of a patient's functional status and prognosis 5–8 . However, 6MWD is affected by individual patients’ physical capability, especially among the elderly with prevalent comorbid conditions 9–11 and, therefore, reliable comparisons of 6MWD can be performed only among patients whose cardiopulmonary capacity is the bottleneck of the distance. The 6MWT also showed considerable variability among individuals 12–15 . Given these considerations, there is a compelling need to introduce new metrics beyond 6MWD to ensure a more comprehensive and consistent evaluation of an exercise capacity and condition in elderly patients with HF. Our spotlight is on the exercise induced desaturation during the 6MWT, namely novel metric averaged decrease in peripheral oxygen saturation during exercise (ΔSpO 2 -Ex), representing the average of the disparity between the maximum SpO 2 in resting phase and the average SpO 2 during the 6MWT. By combining this with the 6MWD, our goal was to present a more exhaustive risk categorization tool for elderly patients with HF. This endeavor could potentially set the foundation for more individualized therapeutic strategies. Results The measurement of ΔSpO 2 -Ex was conducted for 55 patients with HF before discharge between August 2020 and August 2022. Figure 1 shows a representative data of the temporal changes in SpO 2 every second in resting phase and during the 6MWT. The distributions of the 6MWD and ΔSpO 2 -Ex are shown in Figure 2. The mean 6MWD was 237.5 ± 106.7 m and the mean ΔSpO 2 -Ex was 5.8 ± 4.3 %. As shown in Figure3, there was no correlation between the maximum SpO 2 levels in resting phase and ΔSpO 2 -Ex (r=0.06, p=0.66). Similarly, no correlation was found between ΔSpO 2 -Ex and 6MWD (r=-0.04, p=0.782) (Figure S1). For analysis, patients were dichotomized based on their 6MWD and ΔSpO 2 -Ex values. The cut-off values for these classifications were determined using specific cut-off values derived from Receiver Operating Characteristic (ROC) curve analysis. The ΔSpO 2 -Ex cut-off value was set at 6.7 %, leading to classification into small-ΔSpO 2 -Ex (220 m; n=26) and short-6MWD (≤220 m; n=29) groups (Table S1). The baseline characteristics according to the ΔSpO 2 -Ex classification are shown in Table1. The average age of the participants was 80.7 years, and 38 % were female. At the time of the study, the mean body mass index (BMI) was 21.3 kg/m 2 , the average heart rate was 73.1 beats per minute, and the average blood pressure was 111/63 mmHg. 44 % of the participants had coronary artery disease, 31 % had atrial fibrillation, 45 % had hypertension, 16 % had diabetes, and 22 % had pulmonary disease. Laboratory findings included a median N-terminal pro B-type natriuretic peptide (NT-proBNP) level of 3084 pg/mL, a mean creatinine level of 1.8 mg/dL, and a mean glomerular filtration rate (eGFR) of 34.5 mL/min/1.73 m 2 . Echocardiographic measurements showed a mean left ventricular ejection fraction (LVEF) of 45.7 %. From the pulmonary function tests, the percent vital capacity (%VC) and the forced expiratory volume in 1 second as a percentage of predicted (FEV1 %) were determined to be 73.2 % and 74.5 %, respectively. Regarding medication, 49 % were on Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin II receptor blockers (ARB), 45 % on Mineralocorticoid receptor antagonist (MRA), 87 % on β-blockers, 91 % on loop diuretics, and 25 % on Sodium-glucose co-transporter 2 (SGLT2) inhibitors and Angiotensin receptor-neprilysin inhibitor (ARNI). Both ΔSpO 2 -Ex groups showed similar vital signs and medical history, including conditions such as coronary artery disease, valvular disease, atrial fibrillation, and hypertension. Most laboratory and echocardiographic parameters were consistent, except for eGFR. Medication patterns, including the use of ACE inhibitors, β-blockers, and other medications, were consistent across both groups (Table 1). Conversely, the long-6MWD and short-6MWD groups showed similar vital signs and medical histories (Table S2). However, notable differences were observed in laboratory measurements, where the long-6MWD group had lower NT-proBNP levels and higher hematocrit and hemoglobin values compared to the short-6MWD group (NT-proBNP: p=0.006, Hematocrit: p=0.022, Hemoglobin: p=0.008). Echocardiography parameters and pulmonary function tests generally indicated better outcomes for the long-6MWD group. No significant differences were observed in the use of various medications. Prognostic Implications: Kaplan-Meier Analysis and Hazard Ratios Kaplan-Meier analysis indicated that the hazard ratio (HR) for patients in the large-ΔSpO 2 -Ex group was 6.66 (95 % CI: 2.96-15.01; p<0.001), whereas the HR for the short-6MWD group was 2.40 (95 % CI: 1.08-5.32; p=0.031) (Figure4). In analyzing the predictors of rehospitalization due to HF and cardiovascular death within a year after discharge, the univariate analysis showed that ΔSpO 2 -Ex ≥6.7 %, 6MWD ≤220 m, increased heart rate, reduced eGFR, decreased hemoglobin, and decreased %VC were notable predictors. In particular, ΔSpO 2 -Ex stood out with a hazard ratio (HR) of 6.66. In multivariate analysis, the HR for ΔSpO 2 -Ex was an independent risk factor with HR of 6.04 (p<0.001) (Table 2). Composite Risk Stratification When combining ΔSpO 2 -Ex with 6MWD, the rates of cardiac events, including rehospitalization due to HF exacerbation and cardiovascular death within one year, were as follows for each group: 16 % (3/19) for the long-6MWD & small-ΔSpO 2 -Ex group, 47 % (9/19) for the short-6MWD & small-ΔSpO 2 -Ex group, 86 % (6/7) for the long-6MWD & large-ΔSpO 2 -Ex group, and 100 % (10/10) for the short-6MWD & large-ΔSpO 2 -Ex group (Figure 5). Discussion The most significant finding of this study is that ΔSpO 2 -Ex was a strong predictor of rehospitalization among elderly patients with HF and the impact of ΔSpO 2 -Ex is, at least in part, additive to 6MWD; therefore, a combination of these two could provide more powerful predictive information. This is the first study to demonstrate the clinical implications of ΔSpO 2 -Ex in patients with HF. Risk stratification of patients with HF to reduce the risk of rehospitalization remains challenging. Evaluating exercise capacity, an essential factor for determining the severity of HF, is important, but not always straightforward. Historically, the CPET has been regarded as the gold standard for appraising exercise capacity. However, the financial implications, the need for specialized equipment and personnel, and the demands it places on patients, particularly those with more severe HF symptoms, have curtailed its widespread adoption. In addition, a substantial workload beyond the anaerobic threshold is generally required, limiting the number of cases in which CPET can be executed 16,17 . This necessitates a simpler method of assessing submaximal exercise capacity, which is currently fulfilled by the 6MWT and the 6MWD has been widely accepted to be correlated with HF prognosis 5,18–22 . Meanwhile, the 6MWD is affected by orthopedic issues, preventing some patients from undergoing the test. The test also showed considerable variability among individuals; e.g. 6MWD was 381 ± 84 m in the RESOLVD trial 12 , 249.0 ± 113.8 m in the PRESERVED-HF trial 13 , 303.3 ± 105.4 m in the PARALLAX trial 14 and 304.1 ± 111.5 m in the INOVATE-HF trial 15 (Table S3). Likewise, the standard deviation varies among studies, but is substantially large to determine the absolute impact and standard value 23 . Hence, although evaluation of sequential changes in 6MWD within an individual can provide useful longitudinal information about disease severity control with good reproducibility 12–15 , estimation of absolute prognosis of individual cases using 6MWD requires careful attention and in most cases, especially among the elderly, additional evaluation employing other clinical information should be considered 24 . In our study, ΔSpO 2 -Ex was correlated with the prognosis of patients with HF; those with a higher ΔSpO 2 -Ex had significantly more HF rehospitalizations compared to those with a lower ΔSpO 2 -Ex. Importantly, ΔSpO 2 -Ex was not associated with 6MWD, suggesting that ΔSpO 2 -Ex could be a surrogate for pathophysiology different from that of 6MWD, at least in part. This may result in highly accurate predictions of HF readmissions by combining these two values. Because the increase in SV in patients with HF reaches a plateau during milder exercise, cardiac output during exercise is often dependent on the heart rate 25 . However, in patients with HF, the heart rate response during exercise is limited, sometimes due to administration of β blocker, making it difficult to maintain sufficient cardiac output and oxygen supply to meet the elevation of systemic oxygen demand. This is consistent with the finding that ΔSpO 2 -Ex was not associated with LVEF (Table1) because changes in cardiac output during exercise are correlated with SV enlargement and HR elevation, but not with LVEF at rest 26 . Overall, SvO 2 starts to drop at a certain intensity of exercise 27 , and desaturation is supposed to begin at a point where VO 2 cannot fulfill the requirement for oxygenation of venous blood in the lungs. Additionally, it is known that exercise capacity per oxygen consumption is reduced in patients with HF due to progressive deconditioning 28 . In other words, the skeletal muscle oxygen demand for submaximal loading is increased, which may also be a factor in lowering SvO 2 in patients with HF. The decrease in SvO 2 causes hypoxic pulmonary vasoconstriction due to decreased pulmonary tissue oxygen pressure, resulting in reduced oxygen uptake in the lungs. If the left ventricular filling pressure rises during exercise according to underlying left heart disease, subsequent pulmonary edema also limits oxygenation, which is supported by the recent evidence provided by pulmonary echo in patients with HF 29,30 and findings from CardioMEMS 31 . Collectively, ΔSpO 2 -Ex is a value that can be evaluated by integrating such a balance of systemic oxygen demand and supply over the entire 6MWT and is a more comprehensive index of exercise capacity than a simple distance. Measuring ΔSpO 2 -Ex before discharge may serve as a cost-effective, objective, and safe indicator of latent pulmonary congestion. To the best of our knowledge, this is the first study to focus on exercise-induced desaturation during the 6MWT in patients with HF. Previously, exercise-induced desaturation has been investigated in patients with COPD 32–35 . Takigawa et al. studied 144 COPD patients with or without lung volume reduction surgery and found that a reduction in oxygen saturation during the 6MWT, defined by ΔSpO 2 -Ex ≥ 6 % (median of the participants) was an independent predictor of poor prognosis 32 . They also found no correlation between ΔSpO 2 -Ex and 6MWD, which is consistent with our findings. Several studies have also demonstrated a correlation between desaturation during the 6MWT and poor prognosis in COPD patients, although the involvement of patients with HF was not mentioned 32–35 . The underlying mechanism for exercise-induced desaturation in COPD patients is thought to involve hyperinflation leading to insufficient increase in ventilation, as well as insufficient up-regulation of cardiac output and increased peripheral oxygen extraction 35 . Additionally, recent studies have unveiled the importance of latent pulmonary vascular diseases in pulmonary hypertension with left-heart disease, which is revealed by invasive hemodynamic tests under exercise 36 . The results of our study are concordant with those of previous studies because they share, at least in part, the same pathophysiological mechanisms and ΔSpO 2 -Ex is determined as a cumulative surrogate marker for cardiac, pulmonary, and skeletal muscular function, as described above. While this study has shed light on the significant aspects of HF prognosis, it is essential to acknowledge its limitations. The study was confined to a single center and the number of participants was relatively small, which may have affected the generalizability of the results. Our study population was diverse and consisted of patients diagnosed with a range of diseases. Therefore, further research is imperative to accurately determine the predictive effects specific to each primary illness. Our assessments primarily focused on the phase immediately before discharge after acute heart failure treatment, indicating a stable phase. This raises questions about how well our results might translate into an outpatient setting. Additionally, our study was not able to analyze the possibility of HR response suppression be β-blockers due to its design. Further investigation will be required to address this issue. Conclusions As a novel parameter for risk stratification, ΔSpO 2 -Ex might have a substantial predictive impact on the prognosis of patients with elderly HF, especially when it was combined with 6MWD. A larger multicenter study and a deeper understanding of the implications and potential applications of our findings will be required. This research serves as a steppingstone towards enhancing our capabilities in predicting and managing the prognosis of patients with HF in daily practice with minimal resources. Methods Study Design and population This clinical study is single-center, prospective, observational study. We assessed 229 patients aged ≥ 65 years with a confirmed diagnosis of acute HF based on the Framingham criteria between August 2020 and August 2022. The patients were selected based on their readiness for discharge and clinical stability as judged by the board-certified attending cardiologist. Of the initially registered patients, 174 individuals were excluded based on predefined criteria. Exclusion criteria included patient refusal to participate, inability to provide informed consent due to severe communication disorders or cognitive impairments, dependence on physical assistance for walking (excluding mobility aids), unavailability of the wearable pulse oximeter primarily due to prior commitments by other participants, deemed unlikely to complete a 6MWT for reasons unrelated to HF, or presence of missing data. Ultimately, a cohort of 55 patients met the inclusion criteria and underwent evaluation for the study. Ethics approval The study complied with the principles of the Declaration of Helsinki and was approved by the committee of the institutional review board at Hyogo Medical University (approval number: 3531). All patients signed the informed consent forms. Data collection We obtained medical records regarding age, gender, BMI, heart rate, blood pressure, current medications, coronary artery disease, valvular disease, atrial fibrillation, hypertension, diabetes mellitus, and pulmonary disease. We also corrected the data of laboratory examination including serum levels of NT-proBNP, creatinine, eGFR, hematocrit, and the levels of hemoglobin, and echocardiographic data including left ventricular diastolic diameter (LVDd), tricuspid regurgitation jet pressure gradient (TRPG), and LVEF by Teichholz or Simpson’s method. The TRPG was calculated using the simplified Bernoulli equation with tricuspid regurgitation velocity. We obtained medical records regarding rehospitalization due to HF and cardiovascular death within 365 days. If we could not obtain information from the medical records, we collected it by telephone interview. Pulmonary function tests The participants underwent comprehensive pulmonary function tests (PFTs) to assess the lung function. The PFTs were performed using an electric spirometer (DISCOM-21FX; CHEST MI, Tokyo, Japan). The PFTs were performed under the supervision of a certified pulmonary technologist. The primary parameters of interest were %VC and the Forced Expiratory Volume in the first second as a percentage of FEV1 %. The measurement protocols followed the standard guidelines 37 . 6MWT The 6MWT was performed before discharge, after confirming hemodynamic stability. The 6MWT was conducted using a standardized approach 38,39 . In brief, patients were instructed to walk at their own pace while attempting to cover as much ground as possible within six minutes. The participants were allowed to use their usual mobility aids. Experienced physiotherapists timed the walk test, calling out the time every two minutes. They encouraged patients every 30 seconds in a standardized manner, facing the patient and using one of two phrases: “You’re doing well” or “Keep up the good work.” Patients were allowed to slow or stop and rest during the walk but were asked to resume walking as soon as they felt they were able to. ΔSpO 2 -Ex To determine the alterations in SpO 2 with precision, we utilized a wearable pulse oximeter (Fukuda Denshi Co., Ltd., Tokyo, Japan). This device was engineered to record and store SpO 2 values continuously, second by second. Initially, in the first phase, SpO 2 measurements were taken 30 minutes prior to the 6MWT, which was defined as the 'resting phase'. Subsequently, in the second phase, SpO 2 was continuously monitored during the 6MWT to detect any dynamic changes as patients were engaged in the activity. After collecting data from both phases, the maximum SpO 2 during the resting phase and the average SpO 2 during the 6MWT were measured. ΔSpO 2 -Ex was defined as the value obtained by subtracting the averaged SpO 2 during the 6MWT from the maximum SpO 2 in the resting phase. Clinical Outcomes The primary outcome measure was 1-year major adverse cardiovascular outcomes, including rehospitalization due to HF exacerbation, or cardiovascular death. The secondary outcome was a comparison of the usefulness of the 6MWD and ΔSpO 2 -Ex as prognostic factors for patients with HF. Statistical Analysis Patient data are expressed as the mean (standard deviation) or median (interquartile range [IQR]). Baseline characteristics were summarized using descriptive statistics, including means, standard deviations, or percentages, as appropriate. Kaplan-Meier survival analysis was used to evaluate time-to-event data for the primary and secondary outcomes. Hazard ratios (HR) with 95 % confidence intervals (CI) were calculated using a Cox proportional hazards model. A two-tailed p-value of less than 0.05 was considered statistically significant. All statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Japan, version 1.41.1), a modified version of the R commander (version 2.7-1) 40 . Abbreviations 6MWD: Six-Minute Walk Distance 6MWT: Six-Minute Walk Test ACE: Angiotensin-Converting Enzyme ARB: Angiotensin Receptor Blocker ARNI: Angiotensin Receptor-Neprilysin Inhibitor BMI: Body Mass Index CI: Confidence Interval COPD: Chronic Obstructive Pulmonary Disease CPET: Cardiopulmonary Exercise Testing eGFR: estimated Glomerular Filtration Rate FEV1%: Forced Expiratory Volume in 1 second as a percentage of predicted HF: Heart Failure HR: Hazard Ratio LVDd: Left Ventricular Diastolic diameter LVEF: Left Ventricular Ejection Fraction MRA: Mineralocorticoid Receptor Antagonists NT-proBNP: N-terminal Pro B-type Natriuretic Peptide NYHA: New York Heart Association PFTs: Pulmonary Function Tests ROC: Receiver Operating Characteristic SGLT2: Sodium-Glucose Cotransporter 2 SV: Stroke Volume TRPG: Tricuspid Regurgitation jet Pressure Gradient %VC: Percent Vital Capacity Declarations Acknowledgements: None Author contributions I.S. and Y.O. conceived and planned the study design. 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Tables Table 1: Baseline characteristics of Small- and Large-ΔSpO 2 -Ex groups Characteristics All Small-ΔSpO 2 -Ex Large-ΔSpO 2 -Ex P value Subjects, n 55 37 18 - Age, y 80.7 ± 6.7 80.4 ± 7.3 81.6 ± 5.3 0.540 Gender (Female) 25 (45%) 15 (41%) 10 (56%) 0.245 Body mass index, kg/m 2 21.3 ± 4.3 20.7 ± 3.4 22.6 ± 5.7 0.123 Vital signs Heart rate, beats per minute 73.0 ± 15.4 70.9 ± 14.5 77.7 ± 16.7 0.131 Systolic blood pressure, mmHg 111.2 ± 19.0 113.7 ± 18.9 105.6 ± 18.6 0.143 Diastolic blood pressure, mmHg 63.2 ± 11.5 63.2 ± 11.1 61.1 ± 12.5 0.527 Medical history Coronary artery disease, n 24 (44%) 17 (46%) 7 (39%) 1.000 Valvular disease, n 23 (42%) 18 (49%) 5 (28%) 0.250 Atrial fibrillation, n 31 (56%) 22 (59%) 9 (50%) 0.775 Hypertension, n 45 (82%) 31 (84%) 14 (78%) 1.000 Diabetes mellitus, n 16 (29%) 12 (32%) 4 (22%) 0.750 Pulmonary disease, n 12 (22%) 7 (19%) 5 (28%) 0.482 Laboratory measurements NT-proBNP (pg/mL) 3084 (1373, 5781) 2738 (1253, 5133) 4081 (2065, 5843) 0.243 Creatinine (mg/dL) 1.8 ± 1.3 1.7 ± 1.1 2.2 ± 1.6 0.208 eGFR (mL/min/1.73 m 2 ) 34.3 ± 18.3 37.6 ± 19.7 26.9 ± 12.0 0.044 Hematocrit (%) 35.8 ± 6.1 36.0 ± 6.5 35.2 ± 5.2 0.658 Hemoglobin (g/dL) 11.5 ± 2.1 11.7 ± 2.2 11.1 ± 1.8 0.303 Echocardiography parameters LVEF, % 45.7 ± 18.0 44.6 ± 17.6 46.1 ± 19.5 0.916 LVDd, mm 53.9 ± 10.4 53.6 ± 10.8 54.6 ± 9.8 0.729 TRPG, mmHg 26.3 ± 7.1 26.8 ± 6.8 25.4 ± 7.9 0.574 Pulmonary function tests %VC, % 73.2 ± 22.0 72.9 ± 20.8 73.8 ± 25.3 0.890 FEV 1%, % 74.5 ± 11.6 75.0 ± 11.8 73.6 ± 11.6 0.703 Drug therapy ACE inhibitor or ARB, n 27 (49%) 18 (49%) 9 (50%) 0.775 MRA, n 25 (45%) 18 (49%) 7 (39%) 0.773 β-blocker, n 48 (87%) 33 (89%) 15 (83%) 1.000 SGLT2 inhibitor, n 14 (25%) 11 (30%) 3 (17%) 0.510 ARNI, n 14 (25%) 8 (22%) 6 (33%) 0.322 Loop diuretic, n 50 (91%) 34 (92%) 16 (89%) 1.000 6-minute walk test 6MWD (m) 237.5 ± 106.7 238.9 ± 112.2 234.1 ± 96.5 0.878 SpO 2 at rest (%) 98.3 ± 1.5 98.3 ± 1.6 98.3 ± 1.4 0.969 SpO 2 during the 6MWT (%) 92.5 ± 4.4 94.9 ± 2.3 87.2 ± 3.2 <0.001 ΔSpO 2 -Ex (%) 5.8 ± 4.3 3.4 ± 1.7 11.1 ± 3.4 <0.001 Data are presented as the mean ± SD or median with interquartile range (IQR). 6MWD, Six-Minute Walk Distance; ΔSpO 2 -Ex, averaged decrease in peripheral oxygen saturation during exercise; ACE, Angiotensin-converting enzyme; ARB, Angiotensin II receptor blockers; ARNI, Angiotensin receptor-neprilysin inhibitor; eGFR, estimated glomerular filtration rate; FEV1 %, Forced expiratory volume in 1 second as a percentage of predicted; LVDd, Left ventricular end-diastolic dimension; LVEF, Left ventricular ejection fraction; MRA, Mineralocorticoid receptor antagonist; NT-proBNP, N-terminal pro b-type natriuretic peptide; SGLT2, Sodium glucose cotransporter 2; TRPG, Tricuspid regurgitant pressure gradient; %VC, Percent vital capacity. Table 2: Predictors of Cardiovascular events within 1 year after discharge by the Cox Proportional Hazard Model Univariable analysis Multivariable analysis Predictor HR (95% CI) p value HR (95% CI) p value ΔSpO 2 -Ex ≧6.7% 6.66 (2.96-15.01) <0.001 6.04 (2.62-13.92) <0.001 6MWD ≦220m 2.40 (1.08-5.32) 0.031 1.82 (0.70-4.72) 0.218 Age 1.00 (0.95-1.06) 0.978 Gender (Female) 0.72 (0.34-1.51) 0.386 Body mass index 1.07 (0.99-1.16) 0.093 Heart rate 1.03 (1.00-1.05) 0.033 1.03(1.00-1.05) 0.052 Systolic blood pressure 0.99 (0.97-1.01) 0.183 Diastolic blood pressure 0.99 (0.96-1.02) 0.557 Coronary artery disease 0.71 (0.33-1.52) 0.375 Valvular disease 0.91 (0.43-1.95) 0.814 Atrial fibrillation 1.27 (0.59-2.71) 0.539 Hypertension 0.58 (0.23-1.43) 0.234 Diabetes mellitus 0.90 (0.39-2.04) 0.795 Pulmonary disease 1.23 (0.52-2.90) 0.631 NT-proBNP 1.00 (1.00-1.00) 0.525 Creatinine 1.18 (0.94-1.48) 0.161 eGFR 0.97 (0.94-1.00) 0.021 0.98 (0.95-1.01) 0.229 Hemoglobin 0.78 (0.63-0.95) 0.016 0.92 (0.72-1.17) 0.472 LVEF 0.99 (0.97-1.01) 0.306 LVDd 1.00 (0.97-1.04) 0.988 TRPG 1.00 (0.94-1.07) 0.936 %VC 0.97 (0.95-0.99) 0.010 0.97 (0.95-1.00) 0.059 FEV 1% 1.01 (0.98-1.04) 0.643 6MWD, Six-Minute Walk Distance; ΔSpO 2 -Ex, averaged decrease in peripheral oxygen saturation during exercise; eGFR, estimated glomerular filtration rate; FEV1 %, Forced expiratory volume in 1 second as a percentage of predicted; LVDd, Left ventricular end-diastolic dimension; LVEF, Left ventricular ejection fraction; NT-proBNP, N-terminal pro b-type natriuretic peptide; TRPG, Tricuspid regurgitant pressure gradient; %VC, Percent vital capacity. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4173768","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":290781691,"identity":"286e8471-2f2f-4ba7-842b-e3cc57334b39","order_by":0,"name":"Isamu Sunayama","email":"","orcid":"","institution":"Hyogo Medical University","correspondingAuthor":false,"prefix":"","firstName":"Isamu","middleName":"","lastName":"Sunayama","suffix":""},{"id":290781692,"identity":"2181a208-c098-4d13-b631-ddb97940f834","order_by":1,"name":"Kyung-Duk Min","email":"","orcid":"","institution":"Hyogo Medical 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Asakura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYPCCBCBmPobEYWAjRgtbGslaeMyQteAGuu0HGD/+qElL3N5+5ttjngqGaH72BMYPPxj48nBpMTuTwCzNcywncc6Z3O3GPGcYcmf2PGCW7GFgK8ap5UD+B2kGtorEGQy526R52/7nbriRwCAN9EtiAy4t5x8w//zxD6iF/80zoBaG3P03Eph/49VyI4FNgrctJ3GGRA4bWMsGiQQ2/LbceMBmzduXZjxD4pmZ5BygX2acedhm2WOAxy/nE5hv/viWLDuDP/mZxJsKhtz+9uTDN35UHMMZYiiAiQdMMQKdZHAsgSgtjD8Q7BritIyCUTAKRsFIAACGllYiqXFhLgAAAABJRU5ErkJggg==","orcid":"","institution":"Hyogo Medical University","correspondingAuthor":true,"prefix":"","firstName":"Masanori","middleName":"","lastName":"Asakura","suffix":""},{"id":290781705,"identity":"124cabaa-5c33-497a-9198-027fdc8b15ea","order_by":14,"name":"Masaharu Ishihara","email":"","orcid":"","institution":"Hyogo Medical University","correspondingAuthor":false,"prefix":"","firstName":"Masaharu","middleName":"","lastName":"Ishihara","suffix":""}],"badges":[],"createdAt":"2024-03-27 06:14:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4173768/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4173768/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54928873,"identity":"9154b060-ad42-4a0d-a03f-0dfcfbce9aa9","added_by":"auto","created_at":"2024-04-18 17:40:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":78867,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSecond-by-second measurement of SpO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e from resting phase to the end of 6MWT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the first phase, SpO\u003csub\u003e2\u003c/sub\u003e measurements were taken 30 minutes prior to the 6MWT, which was defined as the 'resting phase'. In the second phase, SpO\u003csub\u003e2\u003c/sub\u003e was continuously monitored during the 6MWT to detect any dynamic changes as patients were engaged in the activity.\u003c/p\u003e\n\u003cp\u003e6MWT, Six-Minute Walk Test.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/ce8c3e3ac4415c79920e69c0.png"},{"id":54928876,"identity":"71a94c12-97b2-409f-a689-56070af273b5","added_by":"auto","created_at":"2024-04-18 17:40:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50877,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe distribution of 6MWD and ΔSpO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e-Ex\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(A) Distribution of 6MWD. (B) Distribution of ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex.\u003c/p\u003e\n\u003cp\u003eThe mean 6MWD was 237.5 ± 106.7\u0026nbsp;m and the mean ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex was 5.8 ± 4.3\u0026nbsp;%.\u003c/p\u003e\n\u003cp\u003e6MWD, Six-Minute Walk Distance; ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex, averaged decrease in peripheral oxygen saturation during exercise.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/80f84f2c28225d2192c118e3.png"},{"id":54928875,"identity":"b404fe3f-9732-4c0d-8fdf-bccc551752db","added_by":"auto","created_at":"2024-04-18 17:40:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57703,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe distribution of SpO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e levels in resting phase and ΔSpO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e-Ex\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no correlation between the maximum SpO\u003csub\u003e2\u003c/sub\u003e levels in resting phase and the ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex (r=0.06, p=0.66).\u003c/p\u003e\n\u003cp\u003eΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex, averaged decrease in peripheral oxygen saturation during exercise.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/e1e6edc41ffbeac682db6471.png"},{"id":54929305,"identity":"14463246-c6d9-481f-b52d-31be081bca32","added_by":"auto","created_at":"2024-04-18 17:48:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":131526,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrognostic implications shown by Kaplan-Meier Analysis and Hazard Ratios\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) The Kaplan-Meier analysis of cardiovascular outcomes in long- and short-6MWD group. (B) The Kaplan-Meier analysis of cardiovascular outcomes in small- and large-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group.\u003c/p\u003e\n\u003cp\u003eHR for patients in the large-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group was 6.66 (95 % CI: 2.96-15.01; p\u0026lt;0.001), whereas the HR for the long-6MWD group was 2.40 (95 % CI: 1.08-5.32; p=0.031).\u003c/p\u003e\n\u003cp\u003e6MWD, Six-Minute Walk Distance; ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex, averaged decrease in peripheral oxygen saturation during exercise; CI, confidential interval; HR, hazard ratio.\u0026nbsp;\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/511da2dde3f3d87b5b7d616f.png"},{"id":54928874,"identity":"fcfdedb7-358a-4611-b80c-50ea7c8f13d5","added_by":"auto","created_at":"2024-04-18 17:40:37","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":105902,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIncidence of cardiac events by 6MWD and ΔSpO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e-Ex categories\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen combining ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex with 6MWD, the rates of cardiac events, including heart failure readmission and death within one year, were as follows for each group: 16 % (3/19) for the long-6MWD \u0026amp; small-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group, 47 % (9/19) for the short-6MWD \u0026amp; small-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group, 86 % (6/7) for the long-6MWD \u0026amp; large-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group, and 100 % (10/10) for the short-6MWD \u0026amp; large-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex group.\u003c/p\u003e\n\u003cp\u003e6MWD, Six-Minute Walk Distance; ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex, averaged decrease in peripheral oxygen saturation during exercise.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/ec612e1de4d0c8d648e48043.png"},{"id":62244889,"identity":"6297e185-f61e-407d-8941-024e54b3f914","added_by":"auto","created_at":"2024-08-12 04:29:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1293951,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/9f6c6628-903c-41c1-abc8-c91957d6a095.pdf"},{"id":54928878,"identity":"c8af5000-28fd-4026-96eb-3f6509c58a89","added_by":"auto","created_at":"2024-04-18 17:40:38","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":271088,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4173768/v1/37db22cc81f91b77f3c60753.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Averaged decrease in SpO2 during six-minute walk test as a novel prognostic marker for elderly heart failure patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHeart failure (HF) is estimated to affect 38 million individuals worldwide. Despite notable advancements in treatment over the past couple of decades, HF continues to be a predominant cause of hospitalizations. Because a significant fraction of these hospitalizations is due to acute exacerbation of chronic HF\u003csup\u003e1,\u003c/sup\u003e it is crucial to develop novel approaches to identify high-risk patients who need to be subjected to intense care to prevent rehospitalization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExercise capacity is a widely accepted clinical index that is strongly correlated with the prognosis of patients with HF\u003csup\u003e2\u003c/sup\u003e. The index, including peak VO\u003csub\u003e2\u003c/sub\u003e and anabolic threshold, determined by the cardiopulmonary exercise test (CPET) remains the gold standard to evaluate the exercise capacity and prognosis of patients with HF. Meanwhile, because CPET requires substantial materials and resources, the six minute-walk test (6MWT) is frequently employed as a preferable alternative, as\u0026nbsp;it\u0026nbsp;is a non-invasive and cost-effective test that demonstrates daily activity energy expenditure\u003csup\u003e3,4\u003c/sup\u003e. The distance covered during this test, termed six-minute walk distance (6MWD), is a pivotal index of a patient\u0026apos;s functional status and prognosis\u003csup\u003e5\u0026ndash;8\u003c/sup\u003e.\u0026nbsp;\u0026nbsp;However, 6MWD is affected by individual patients\u0026rsquo; physical capability, especially among the elderly with prevalent comorbid conditions\u003csup\u003e9\u0026ndash;11\u003c/sup\u003e and, therefore, reliable comparisons of 6MWD can be performed only among patients whose cardiopulmonary capacity is the bottleneck of the distance.\u0026nbsp;The 6MWT also showed considerable variability among individuals\u003csup\u003e12\u0026ndash;15\u003c/sup\u003e.\u0026nbsp;Given these considerations, there is a compelling need to introduce new metrics beyond 6MWD to ensure a more comprehensive and consistent evaluation of an exercise capacity and condition in elderly patients with HF.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur spotlight is on the exercise induced desaturation during the 6MWT, namely novel metric\u0026nbsp;averaged decrease in peripheral oxygen saturation during exercise (\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex), representing the average of the disparity between the maximum SpO\u003csub\u003e2\u003c/sub\u003e in resting phase and the average SpO\u003csub\u003e2\u003c/sub\u003e during the 6MWT. By combining this with the 6MWD, our goal was to present a more exhaustive risk categorization tool for elderly patients with HF. This endeavor could potentially set the foundation for more individualized therapeutic strategies.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe measurement of \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was conducted for 55 patients with HF before discharge between August 2020 and August 2022. Figure 1 shows a representative data of the temporal changes in SpO\u003csub\u003e2\u003c/sub\u003e every second in resting phase and during the 6MWT.\u003c/p\u003e\n\u003cp\u003eThe distributions of the 6MWD and \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex are shown in Figure 2. \u0026nbsp;The mean 6MWD was 237.5\u0026nbsp;\u0026plusmn; 106.7 m and the mean \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was 5.8\u0026nbsp;\u0026plusmn; 4.3 %. As shown in Figure3, there was no correlation between the maximum SpO\u003csub\u003e2\u003c/sub\u003e levels in resting phase and \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex (r=0.06, p=0.66). Similarly, no correlation was found between \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex and 6MWD (r=-0.04, p=0.782) (Figure S1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor analysis, patients were dichotomized based on their 6MWD and \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex values. The cut-off values for these classifications were determined\u0026nbsp;using specific cut-off values derived from Receiver Operating Characteristic (ROC) curve analysis. The \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex cut-off value was set at 6.7 %, leading to classification into small-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex (\u0026lt;6.7 %; n=37) and large-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex (\u0026ge;6.7 %; n=18) groups, and the 6MWD cut-off value was established at 220 m, leading to classification into long-6MWD (\u0026gt;220 m; n=26) and short-6MWD (\u0026le;220 m; n=29) groups (Table S1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics according to the\u0026nbsp;\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex classification are shown in Table1. The average age of the participants was 80.7 years, and 38 % were female. At the time of the study, the mean body mass index (BMI) was 21.3 kg/m\u003csup\u003e2\u003c/sup\u003e, the average heart rate was 73.1 beats per minute, and the average blood pressure was 111/63 mmHg. 44 % of the participants had coronary artery disease, 31 % had atrial fibrillation, 45 % had hypertension, 16 % had diabetes, and 22 % had pulmonary disease.\u0026nbsp;Laboratory findings included a median N-terminal pro B-type natriuretic peptide (NT-proBNP) level of 3084 pg/mL, a mean creatinine level of 1.8 mg/dL, and a mean glomerular filtration rate (eGFR) of 34.5 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e. Echocardiographic measurements showed a mean left ventricular ejection fraction (LVEF) of 45.7 %.\u0026nbsp;From the pulmonary function tests, the\u0026nbsp;percent vital capacity\u0026nbsp;(%VC) and the forced expiratory volume in 1 second as a percentage of predicted (FEV1 %) were determined to be 73.2 % and 74.5 %, respectively.\u0026nbsp;Regarding medication, 49 % were on\u0026nbsp;Angiotensin-converting enzyme\u0026nbsp;(ACE) inhibitors or\u0026nbsp;Angiotensin II receptor blockers\u0026nbsp;(ARB), 45 % on\u0026nbsp;Mineralocorticoid receptor antagonist\u0026nbsp;(MRA), 87 % on \u0026beta;-blockers, 91 % on loop diuretics, and 25 % on\u0026nbsp;Sodium-glucose co-transporter 2 (SGLT2) inhibitors and\u0026nbsp;Angiotensin receptor-neprilysin inhibitor\u0026nbsp;(ARNI).\u0026nbsp;Both \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex groups showed similar vital signs and medical history, including conditions such as coronary artery disease, valvular disease, atrial fibrillation, and hypertension. Most laboratory and echocardiographic parameters were consistent, except for eGFR. Medication patterns, including the use of ACE inhibitors, \u0026beta;-blockers, and other medications, were consistent across both groups (Table 1).\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConversely, the long-6MWD and short-6MWD groups showed similar vital signs and medical histories (Table S2). However, notable differences were observed in laboratory measurements, where the long-6MWD group had lower NT-proBNP levels and higher hematocrit and hemoglobin values compared to the short-6MWD group (NT-proBNP: p=0.006, Hematocrit: p=0.022, Hemoglobin: p=0.008). Echocardiography parameters and pulmonary function tests generally indicated better outcomes for the long-6MWD group. No significant differences were observed in the use of various medications.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrognostic Implications: Kaplan-Meier Analysis and Hazard Ratios\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKaplan-Meier analysis indicated that the hazard ratio (HR) for patients in the large-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex group was 6.66 (95 % CI: 2.96-15.01; p\u0026lt;0.001), whereas the HR for the short-6MWD group was 2.40 (95 % CI: 1.08-5.32; p=0.031) (Figure4).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In analyzing the predictors of rehospitalization due to HF and cardiovascular death within a year after discharge, the univariate analysis showed that \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex\u0026nbsp;\u0026ge;6.7 %, 6MWD\u0026nbsp;\u0026le;220 m, increased heart rate, reduced eGFR, decreased hemoglobin, and decreased %VC were notable predictors. In particular, \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex stood out with a hazard ratio (HR) of 6.66.\u0026nbsp;\u0026nbsp;In multivariate analysis, the HR for \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was an independent risk factor\u0026nbsp;with HR of 6.04 (p\u0026lt;0.001) (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposite Risk Stratification\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhen combining \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex with 6MWD, the rates of cardiac events, including\u0026nbsp;rehospitalization due to HF exacerbation and cardiovascular death\u0026nbsp;within one year, were as follows for each group: 16 % (3/19) for the long-6MWD \u0026amp; small-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex group, 47 % (9/19) for the short-6MWD \u0026amp; small-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex group, 86 % (6/7) for the long-6MWD \u0026amp; large-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex group, and 100 % (10/10) for the short-6MWD \u0026amp; large-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex group (Figure 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe most significant finding of this study is that \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was a strong predictor of rehospitalization among elderly patients with HF and the impact of \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex is, at least in part, additive to 6MWD; therefore, a combination of these two could provide more powerful predictive information. This is the first study to demonstrate the clinical implications of \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex in patients with HF.\u003c/p\u003e\n\u003cp\u003eRisk stratification of patients with HF to reduce the risk of rehospitalization remains challenging. Evaluating exercise capacity, an essential factor for determining the severity of HF, is important, but not always straightforward. Historically, the CPET has been regarded as the gold standard for appraising exercise capacity. However, the financial implications, the need for specialized equipment and personnel, and the demands it places on patients, particularly those with more severe HF symptoms, have curtailed its widespread adoption. In addition, a substantial workload beyond the anaerobic threshold is generally required, limiting the number of cases in which CPET can be executed\u003csup\u003e16,17\u003c/sup\u003e. This necessitates a simpler method of assessing submaximal exercise capacity, which is currently fulfilled by the 6MWT and the 6MWD has been widely accepted to be correlated with HF prognosis\u003csup\u003e5,18\u0026ndash;22\u003c/sup\u003e. Meanwhile, the 6MWD is affected by orthopedic issues, preventing some patients from undergoing the test. The test also showed considerable variability among individuals; e.g. 6MWD was 381 \u0026plusmn; 84 m in the RESOLVD trial\u003csup\u003e12\u003c/sup\u003e, 249.0 \u0026plusmn; 113.8 m in the PRESERVED-HF trial\u003csup\u003e13\u003c/sup\u003e , 303.3 \u0026plusmn; 105.4 m in the PARALLAX trial\u003csup\u003e14\u003c/sup\u003e and 304.1 \u0026plusmn; 111.5 m in the INOVATE-HF trial\u003csup\u003e15\u003c/sup\u003e (Table S3). Likewise, the standard deviation varies among studies, but is substantially large to determine the absolute impact and standard value\u003csup\u003e23\u003c/sup\u003e.\u0026nbsp;Hence, although evaluation of sequential changes in 6MWD within an individual can provide useful longitudinal information about disease severity control with good reproducibility\u003csup\u003e12\u0026ndash;15\u003c/sup\u003e, estimation of absolute prognosis of individual cases using 6MWD requires careful attention and in most cases, especially among the elderly, additional evaluation employing other clinical information should be considered\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn our study, \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was correlated with the prognosis of patients with HF; those with a higher \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex had significantly more HF rehospitalizations compared to those with a lower \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex. Importantly, \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was not associated with 6MWD, suggesting that \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex could be a surrogate for pathophysiology different from that of 6MWD, at least in part. This may result in highly accurate predictions of HF readmissions by combining these two values. Because the increase in SV in patients with HF reaches a plateau during milder exercise, cardiac output during exercise is often dependent on the heart rate\u003csup\u003e25\u003c/sup\u003e. However, in patients with HF, the heart rate response during exercise is limited, sometimes due to administration of\u0026nbsp;\u0026beta; blocker,\u0026nbsp;making it difficult to maintain sufficient cardiac output and oxygen supply to meet the elevation of systemic oxygen demand. This is consistent with the finding that \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was not associated with LVEF (Table1) because changes in cardiac output during exercise are correlated with SV enlargement and HR elevation, but not with LVEF at rest\u003csup\u003e26\u003c/sup\u003e. Overall, SvO\u003csub\u003e2\u003c/sub\u003e starts to drop at a certain intensity of exercise\u003csup\u003e27\u003c/sup\u003e, and desaturation is supposed to begin at a point where VO\u003csub\u003e2\u003c/sub\u003e cannot fulfill the requirement for oxygenation of venous blood in the lungs. Additionally, it is known that exercise capacity per oxygen consumption is reduced in patients with HF due to progressive deconditioning\u003csup\u003e28\u003c/sup\u003e. In other words, the skeletal muscle oxygen demand for submaximal loading is increased, which may also be a factor in lowering SvO\u003csub\u003e2\u003c/sub\u003e in patients with HF. The decrease in SvO\u003csub\u003e2\u003c/sub\u003e causes hypoxic pulmonary vasoconstriction due to decreased pulmonary tissue oxygen pressure, resulting in reduced oxygen uptake in the lungs. If the left ventricular filling pressure rises during exercise according to underlying left heart disease, subsequent pulmonary edema also limits oxygenation, which is supported by the recent evidence provided by pulmonary echo in patients with HF\u003csup\u003e29,30\u003c/sup\u003e and findings from CardioMEMS\u003csup\u003e31\u003c/sup\u003e. Collectively, \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex is a value that can be evaluated by integrating such a balance of systemic oxygen demand and supply over the entire 6MWT and is a more comprehensive index of exercise capacity than a simple distance. Measuring \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex before discharge may serve as a cost-effective, objective, and safe indicator of latent pulmonary congestion.\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this is the first study to focus on exercise-induced desaturation during the 6MWT in patients with HF. Previously, exercise-induced desaturation has been investigated in patients with COPD\u003csup\u003e32\u0026ndash;35\u003c/sup\u003e. Takigawa et al. studied 144 COPD patients with or without lung volume reduction surgery and found that a reduction in oxygen saturation during the 6MWT, defined by \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex\u0026nbsp;\u0026ge;\u0026nbsp;6 % (median of the participants) was an independent predictor of poor prognosis\u003csup\u003e32\u003c/sup\u003e. They also found no correlation between \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex and 6MWD, which is consistent with our findings. Several studies have also demonstrated a correlation between desaturation during the 6MWT and poor prognosis in COPD patients, although the involvement of patients with HF was not mentioned\u003csup\u003e32\u0026ndash;35\u003c/sup\u003e. The underlying mechanism for exercise-induced desaturation in COPD patients is thought to involve hyperinflation leading to insufficient increase in ventilation, as well as insufficient up-regulation of cardiac output and increased peripheral oxygen extraction\u003csup\u003e35\u003c/sup\u003e. Additionally, recent studies have unveiled the importance of latent pulmonary vascular diseases in pulmonary hypertension with left-heart disease, which is revealed by invasive hemodynamic tests under exercise\u0026nbsp;\u003csup\u003e36\u003c/sup\u003e. The results of our study are concordant with those of previous studies because they share, at least in part, the same pathophysiological mechanisms and \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex is determined as a cumulative surrogate marker for cardiac, pulmonary, and skeletal muscular function, as described above. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhile this study has shed light on the significant aspects of HF prognosis, it is essential to acknowledge its limitations. The study was confined to a single center and the number of participants was relatively small, which may have affected the generalizability of the results. Our study population was diverse and consisted of patients diagnosed with a range of diseases. Therefore, further research is imperative to accurately determine the predictive effects specific to each primary illness. Our assessments primarily focused on the phase immediately before discharge after acute heart failure treatment, indicating a stable phase. This raises questions about how well our results might translate into an outpatient setting. Additionally, our study was not able to analyze the possibility of HR response suppression be \u0026beta;-blockers due to its design.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Further investigation will be required to address this issue.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAs a novel parameter for risk stratification, \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex might have a substantial predictive impact on the prognosis of patients with elderly HF, especially when it was combined with 6MWD. A larger multicenter study and a deeper understanding of the implications and potential applications of our findings will be required. This research serves as a steppingstone towards enhancing our capabilities in predicting and managing the prognosis of patients with HF in daily practice with minimal resources.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and population\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis clinical study is single-center, prospective, observational study. We assessed 229 patients aged \u0026ge; 65 years with a confirmed diagnosis of acute HF based on the Framingham criteria between August 2020 and August 2022. The patients were selected based on their readiness for discharge and clinical stability as judged by the board-certified attending cardiologist. Of the initially registered patients, 174 individuals were excluded based on predefined criteria. Exclusion criteria included patient refusal to participate, inability to provide informed consent due to severe communication disorders or cognitive impairments, dependence on physical assistance for walking (excluding mobility aids), unavailability of the wearable pulse oximeter primarily due to prior commitments by other participants, deemed unlikely to complete a 6MWT for reasons unrelated to HF, or presence of missing data. Ultimately, a cohort of 55 patients met the inclusion criteria and underwent evaluation for the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study complied with the principles of the Declaration of Helsinki and was approved by the committee of the institutional review board at Hyogo Medical University (approval number: 3531). All patients signed the informed consent forms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe obtained medical records regarding age, gender, BMI, heart rate, blood pressure, current medications, coronary artery disease, valvular disease, atrial fibrillation, hypertension, diabetes mellitus, and pulmonary disease. We also corrected the data of laboratory examination including serum levels of NT-proBNP, creatinine, eGFR, hematocrit, and the levels of hemoglobin, and echocardiographic data including left ventricular diastolic diameter (LVDd), tricuspid regurgitation jet pressure gradient (TRPG), and LVEF by Teichholz or Simpson\u0026rsquo;s method. The TRPG was calculated using the simplified Bernoulli equation with tricuspid regurgitation velocity. We obtained medical records regarding rehospitalization due to HF and cardiovascular death within 365 days. If we could not obtain information from the medical records, we collected it by telephone interview.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePulmonary function tests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe participants underwent comprehensive pulmonary function tests (PFTs) to assess the lung function.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe PFTs were performed using an electric spirometer (DISCOM-21FX; CHEST MI, Tokyo, Japan). The PFTs were performed under the supervision of a certified pulmonary technologist. The primary parameters of interest were %VC and the Forced Expiratory Volume in the first second as a percentage of FEV1 %.\u0026nbsp;\u0026nbsp;The measurement protocols followed the standard guidelines\u003csup\u003e37\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6MWT\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 6MWT was performed before discharge, after confirming hemodynamic stability.\u0026nbsp;\u0026nbsp;The 6MWT was conducted using a standardized approach\u003csup\u003e38,39\u003c/sup\u003e.\u0026nbsp; In brief, patients\u0026nbsp;were instructed to walk at their own pace while attempting to cover as much ground as possible within six minutes. The participants were allowed to use their usual mobility aids. Experienced physiotherapists timed the walk test, calling out the time every two minutes. They encouraged patients every 30 seconds in a standardized manner, facing the patient and using one of two phrases: \u0026ldquo;You\u0026rsquo;re doing well\u0026rdquo; or \u0026ldquo;Keep up the good work.\u0026rdquo; Patients were allowed to slow or stop and rest during the walk but were asked to resume walking as soon as they felt they were able to.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003cstrong\u003e-Ex\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo determine the alterations in SpO\u003csub\u003e2\u003c/sub\u003e with precision, we utilized a wearable pulse oximeter (Fukuda Denshi Co., Ltd., Tokyo, Japan). This device was engineered to record and store SpO\u003csub\u003e2\u003c/sub\u003e values continuously, second by second.\u0026nbsp;\u0026nbsp;Initially, in the first phase, SpO\u003csub\u003e2\u003c/sub\u003e measurements were taken 30 minutes prior to the 6MWT, which was defined as the \u0026apos;resting phase\u0026apos;. Subsequently, in the second phase, SpO\u003csub\u003e2\u003c/sub\u003e was continuously monitored during the 6MWT to detect any dynamic changes as patients were engaged in the activity.\u0026nbsp;After collecting data from both phases, the maximum SpO\u003csub\u003e2\u003c/sub\u003e during the resting phase and the average SpO\u003csub\u003e2\u003c/sub\u003e during the 6MWT were measured. \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex was defined as the value obtained by subtracting the averaged SpO\u003csub\u003e2\u003c/sub\u003e during the 6MWT from the maximum SpO\u003csub\u003e2\u003c/sub\u003e in the resting phase.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Outcomes\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was 1-year major adverse cardiovascular outcomes, including rehospitalization due to HF exacerbation, or cardiovascular death. The secondary outcome was a comparison of the usefulness of the 6MWD and \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex as prognostic factors for patients with HF.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient data are expressed as the mean (standard deviation) or median (interquartile range [IQR]).\u0026nbsp;Baseline characteristics were summarized using descriptive statistics, including means, standard deviations, or percentages, as appropriate. Kaplan-Meier survival analysis was used to evaluate time-to-event data for the primary and secondary outcomes. Hazard ratios (HR) with 95 % confidence intervals (CI) were calculated using a Cox proportional hazards model. A two-tailed p-value of less than 0.05 was considered statistically significant.\u0026nbsp;\u0026nbsp;All statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Japan, version 1.41.1),\u0026nbsp;a modified version of the R commander (version 2.7-1)\u003csup\u003e40\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e6MWD: Six-Minute Walk Distance\u003c/p\u003e\n\u003cp\u003e6MWT: Six-Minute Walk Test\u003c/p\u003e\n\u003cp\u003eACE: Angiotensin-Converting Enzyme\u003c/p\u003e\n\u003cp\u003eARB: Angiotensin Receptor Blocker\u003c/p\u003e\n\u003cp\u003eARNI: Angiotensin Receptor-Neprilysin Inhibitor\u003c/p\u003e\n\u003cp\u003eBMI: Body Mass Index\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e\n\u003cp\u003eCOPD: Chronic Obstructive Pulmonary Disease\u003c/p\u003e\n\u003cp\u003eCPET: Cardiopulmonary Exercise Testing\u003c/p\u003e\n\u003cp\u003eeGFR: estimated Glomerular Filtration Rate\u003c/p\u003e\n\u003cp\u003eFEV1%: Forced Expiratory Volume in 1 second as a percentage of predicted\u003c/p\u003e\n\u003cp\u003eHF: Heart Failure\u003c/p\u003e\n\u003cp\u003eHR: Hazard Ratio\u003c/p\u003e\n\u003cp\u003eLVDd: Left Ventricular Diastolic diameter\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLVEF: Left Ventricular Ejection Fraction\u003c/p\u003e\n\u003cp\u003eMRA: Mineralocorticoid Receptor Antagonists\u003c/p\u003e\n\u003cp\u003eNT-proBNP: N-terminal Pro B-type Natriuretic Peptide\u003c/p\u003e\n\u003cp\u003eNYHA: New York Heart Association\u003c/p\u003e\n\u003cp\u003ePFTs: Pulmonary Function Tests\u003c/p\u003e\n\u003cp\u003eROC: Receiver Operating Characteristic\u003c/p\u003e\n\u003cp\u003eSGLT2: Sodium-Glucose Cotransporter 2\u003c/p\u003e\n\u003cp\u003eSV: Stroke Volume\u003c/p\u003e\n\u003cp\u003eTRPG: Tricuspid Regurgitation jet Pressure Gradient\u003c/p\u003e\n\u003cp\u003e%VC: Percent Vital Capacity\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI.S. and Y.O. conceived and planned the study design.\u003c/p\u003e\n\u003cp\u003eI.S., K.M., Y.O., J.O., Y.M., A.D., Y.S, E.M., M.O., K.A., M.S., A.E. and Y.N. contributed to case enrollment and data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eI.S., K.M., M.A., and M.I. contributed to the interpretation of the results. \u0026nbsp;I.S., K.M., M.A. and M.I. wrote the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors provided critical feedback and helped shape the research, analysis and manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interest:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKomajda, M. \u003cem\u003eet al.\u003c/em\u003e The EuroHeart Failure survey programme - A survey on the quality of care among patients with heart failure in Europe. 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The association of 6-minute walk performance and outcomes in stable outpatients with heart failure. \u003cem\u003eJ Card Fail\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, (2004).\u003c/li\u003e\n\u003cli\u003eTroosters, T., Gosselink, R. \u0026amp; Decramer, M. Six minute walking distance in healthy elderly subjects. \u003cem\u003eEuropean Respiratory Journal\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, (1999).\u003c/li\u003e\n\u003cli\u003eFaggiano, P., D\u0026rsquo;Aloia, A., Gualeni, A., Brentana, L. \u0026amp; Dei Cas, L. 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Prognostic value of walk distance, work, oxygen saturation, and dyspnea during 6-minute walk test in COPD patients. \u003cem\u003eRespir Care\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e, (2013).\u003c/li\u003e\n\u003cli\u003eWaatevik, M. \u003cem\u003eet al.\u003c/em\u003e Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD. \u003cem\u003eEuropean Respiratory Journal\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, (2016).\u003c/li\u003e\n\u003cli\u003eCaravita, S. \u003cem\u003eet al.\u003c/em\u003e Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction. \u003cem\u003eJACC Heart Fail\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, (2023).\u003c/li\u003e\n\u003cli\u003eKubota, M. \u003cem\u003eet al.\u003c/em\u003e Reference values for spirometry, including vital capacity, in Japanese adults calculated with the LMS method and compared with previous values. \u003cem\u003eRespir Investig\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, (2014).\u003c/li\u003e\n\u003cli\u003eGuyatt, G. H. \u003cem\u003eet al.\u003c/em\u003e Effect of encouragement on walking test performance. \u003cem\u003eThorax\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 818\u0026ndash;822 (1984).\u003c/li\u003e\n\u003cli\u003eGuyatt, G. H. \u003cem\u003eet al.\u003c/em\u003e The 6-minute walk: A new measure of exercise capacity in patients with chronic heart failure. \u003cem\u003eCan Med Assoc J\u003c/em\u003e \u003cstrong\u003e132\u003c/strong\u003e, (1985).\u003c/li\u003e\n\u003cli\u003eKanda, Y. Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. \u003cem\u003eBone Marrow Transplant\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, (2013).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Baseline characteristics of Small- and Large-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmall-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLarge-\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eSubjects, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e37\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eAge, y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e80.7 \u0026plusmn; 6.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e80.4 \u0026plusmn; 7.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e81.6 \u0026plusmn; 5.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.540\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eGender (Female)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;25 (45%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e15 (41%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e10 (56%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.245\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e21.3 \u0026plusmn; 4.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e20.7 \u0026plusmn; 3.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e22.6 \u0026plusmn; 5.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.123\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eVital signs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Heart rate, beats per minute\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e73.0 \u0026plusmn; 15.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e70.9 \u0026plusmn; 14.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e77.7 \u0026plusmn; 16.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.131\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Systolic blood pressure, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e111.2 \u0026plusmn; 19.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e113.7 \u0026plusmn; 18.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e105.6 \u0026plusmn; 18.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.143\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Diastolic blood pressure, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e63.2 \u0026plusmn; 11.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e63.2 \u0026plusmn; 11.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e61.1 \u0026plusmn; 12.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.527\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eMedical history\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Coronary artery disease, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e24 (44%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e17 (46%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e7 (39%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Valvular disease, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e23 (42%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e18 (49%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e5 (28%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.250\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Atrial fibrillation, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e31 (56%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e22 (59%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e9 (50%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.775\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Hypertension, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e45 (82%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e31 (84%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e14 (78%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Diabetes mellitus, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e16 (29%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;12 (32%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;4 (22%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.750\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Pulmonary disease, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e12 (22%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e7 (19%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;5 (28%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.482\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eLaboratory measurements\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e \u0026nbsp;NT-proBNP (pg/mL)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e3084\u003c/p\u003e\n \u003cp\u003e(1373, 5781)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e2738\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(1253, 5133)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e4081\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(2065, 5843)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.243\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Creatinine (mg/dL)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;1.8 \u0026plusmn; 1.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e1.7 \u0026plusmn; 1.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e2.2 \u0026plusmn; 1.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.208\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; eGFR (mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e34.3 \u0026plusmn; 18.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e37.6 \u0026plusmn; 19.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e26.9 \u0026plusmn; 12.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.044\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Hematocrit (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e35.8 \u0026plusmn; 6.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e36.0 \u0026plusmn; 6.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e35.2 \u0026plusmn; 5.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.658\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Hemoglobin (g/dL)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e11.5 \u0026plusmn; 2.1 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e11.7 \u0026plusmn; 2.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e11.1 \u0026plusmn; 1.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.303\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eEchocardiography parameters\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e LVEF, %\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e45.7 \u0026plusmn; 18.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e44.6 \u0026plusmn; 17.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e46.1 \u0026plusmn; 19.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.916\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e LVDd, mm\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e53.9 \u0026plusmn; 10.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e53.6 \u0026plusmn; 10.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e54.6 \u0026plusmn; 9.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.729\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e TRPG, mmHg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e26.3 \u0026plusmn; 7.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e26.8 \u0026plusmn; 6.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e25.4 \u0026plusmn; 7.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.574\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003ePulmonary function tests\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e %VC, %\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e73.2 \u0026plusmn; 22.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e72.9 \u0026plusmn; 20.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e73.8 \u0026plusmn; 25.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.890\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e FEV 1%, %\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e74.5 \u0026plusmn; 11.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e75.0 \u0026plusmn; 11.8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e73.6 \u0026plusmn; 11.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.703\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003eDrug therapy \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e ACE inhibitor or ARB, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e27 (49%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e18 (49%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e9 (50%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.775\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e MRA, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e25 (45%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e18 (49%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e7 (39%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.773\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e \u0026beta;-blocker, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e48 (87%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e33 (89%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e15 (83%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e SGLT2 inhibitor, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e14 (25%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e11 (30%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;3 (17%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.510\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e ARNI, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e14 (25%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e8 (22%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e6 (33%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.322\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e Loop diuretic, n\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e50 (91%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e34 (92%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e16 (89%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e6-minute walk test\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e 6MWD (m)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e237.5 \u0026plusmn; 106.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e238.9 \u0026plusmn; 112.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e234.1 \u0026plusmn; 96.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.878\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e SpO\u003csub\u003e2\u003c/sub\u003e at rest (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e98.3 \u0026plusmn; 1.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e98.3 \u0026plusmn; 1.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e98.3 \u0026plusmn; 1.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e0.969\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e SpO\u003csub\u003e2\u003c/sub\u003e during the 6MWT (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e92.5 \u0026plusmn; 4.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e94.9 \u0026plusmn; 2.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e87.2 \u0026plusmn; 3.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.32%\" valign=\"top\"\u003e\n \u003cp\u003e \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2%\" valign=\"top\"\u003e\n \u003cp\u003e5.8 \u0026plusmn; 4.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e3.4 \u0026plusmn; 1.7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.68%\" valign=\"top\"\u003e\n \u003cp\u003e11.1 \u0026plusmn; 3.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.12%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData are presented as the mean \u0026plusmn; SD or median with interquartile range (IQR). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6MWD,\u0026nbsp;Six-Minute Walk Distance; \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex,\u0026nbsp;averaged decrease in peripheral oxygen saturation during exercise; ACE, Angiotensin-converting enzyme; ARB, Angiotensin II receptor blockers; ARNI, Angiotensin receptor-neprilysin inhibitor; eGFR, estimated glomerular filtration rate; FEV1 %, Forced expiratory volume in 1 second as a percentage of predicted; LVDd, Left ventricular end-diastolic dimension; LVEF, Left ventricular ejection fraction; MRA, Mineralocorticoid receptor antagonist; NT-proBNP, N-terminal pro b-type natriuretic peptide; SGLT2, Sodium glucose cotransporter 2; TRPG, Tricuspid regurgitant pressure gradient; %VC, Percent vital capacity.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Predictors of Cardiovascular events within 1 year after discharge by the Cox Proportional Hazard Model\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.3801652892562%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.3801652892562%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictor\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex\u0026nbsp;≧6.7%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e6.66 (2.96-15.01)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e6.04 (2.62-13.92)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003e6MWD\u0026nbsp;≦220m\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e2.40 (1.08-5.32)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.031\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.82 (0.70-4.72)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.218\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.00 (0.95-1.06)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.978\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eGender (Female)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.72 (0.34-1.51)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.386\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eBody mass index\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.07 (0.99-1.16)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.093\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eHeart rate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.03 (1.00-1.05)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.033\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.03(1.00-1.05)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.052\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic blood pressure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.99 (0.97-1.01) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.183\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eDiastolic blood pressure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.99 (0.96-1.02)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.557\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eCoronary artery disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.71 (0.33-1.52)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.375\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eValvular disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.91 (0.43-1.95)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.814\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eAtrial fibrillation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.27 (0.59-2.71)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.539\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.58 (0.23-1.43)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.234\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes mellitus\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.90 (0.39-2.04)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.795\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003ePulmonary disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.23 (0.52-2.90)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.631\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eNT-proBNP\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.00 (1.00-1.00)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.525\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eCreatinine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.18 (0.94-1.48)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.161\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eeGFR\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.97 (0.94-1.00)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.021\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.98 (0.95-1.01)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.229\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eHemoglobin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.78 (0.63-0.95)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.016\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.92 (0.72-1.17)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.472\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eLVEF\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.99 (0.97-1.01)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.306\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eLVDd\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.00 (0.97-1.04)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.988\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eTRPG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.00 (0.94-1.07)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.936\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003e%VC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.97 (0.95-0.99)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.010\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e0.97 (0.95-1.00)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.059\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.611570247933884%\" valign=\"top\"\u003e\n \u003cp\u003eFEV 1%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e1.01 (0.98-1.04)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.643\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.628099173553719%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.330578512396695%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6MWD, Six-Minute Walk Distance; \u0026Delta;SpO\u003csub\u003e2\u003c/sub\u003e-Ex, averaged decrease in peripheral oxygen saturation during exercise; eGFR, estimated glomerular filtration rate; FEV1 %, Forced expiratory volume in 1 second as a percentage of predicted; LVDd, Left ventricular end-diastolic dimension; LVEF, Left ventricular ejection fraction; NT-proBNP, N-terminal pro b-type natriuretic peptide; TRPG, Tricuspid regurgitant pressure gradient; %VC, Percent vital capacity.\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Heart failure, six-minute walk test, peripheral oxygen saturation, prognostic marker, rehospitalization.","lastPublishedDoi":"10.21203/rs.3.rs-4173768/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4173768/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Exercise capacity is pivotal in risk stratification in heart failure (HF) and the six-minute walk test (6MWT) is often employed to evaluate it, but estimation of the absolute risk in elderly patients through six-minute walk distance (6MWD) is difficult due to comorbidities resulting in wide variability among individuals, implicating unmet-needs for comprehensive index for exercise capacity in the elderly.\u003c/p\u003e\n\u003cp\u003eMethods: During the 6MWT, 6MWD and exercise-induced changes in peripheral oxygen saturation (ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex) were measured. The associations between these parameters and cardiovascular outcomes, including HF rehospitalization and cardiovascular death within one year after discharge were assessed.\u003c/p\u003e\n\u003cp\u003eResults: Fifty-five HF patients with age \u0026gt; 65 yeas were investigated. The mean 6MWD was 237.5 m, and the mean ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex was 5.8 %. Kaplan-Meier analysis revealed a significant correlation between larger ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex and adverse cardiovascular outcomes (HR 6.66, p\u0026lt;0.001) compared to 6MWD (HR 2.40, p=0.031). In multivariate analysis, ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex was an independent risk factor. The combination of short-6MWD and large-ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex identified patients with markedly high incidence rate of cardiovascular events.\u003c/p\u003e\n\u003cp\u003eConclusions: ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex could be an independent prognostic marker for HF patients, surpassing the predictive power of 6MWD, suggesting that the 6MWT can provide a novel prognostic assessment that reflects exercise capacity through ΔSpO\u003csub\u003e2\u003c/sub\u003e-Ex.\u003c/p\u003e","manuscriptTitle":"Averaged decrease in SpO2 during six-minute walk test as a novel prognostic marker for elderly heart failure patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-18 17:40:33","doi":"10.21203/rs.3.rs-4173768/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9302f068-6110-47bc-ba53-05da180db7f5","owner":[],"postedDate":"April 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":30633475,"name":"Health sciences/Cardiology/Cardiovascular biology/Cardiovascular diseases/Heart failure"},{"id":30633476,"name":"Health sciences/Biomarkers/Prognostic markers"}],"tags":[],"updatedAt":"2024-08-12T04:21:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-18 17:40:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4173768","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4173768","identity":"rs-4173768","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}