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 guidelines37.
6MWT
The 6MWT was performed before discharge, after confirming hemodynamic stability. The 6MWT was conducted using a standardized approach38,39. 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.
ΔSpO2-Ex
To determine the alterations in SpO2 with precision, we utilized a wearable pulse oximeter (Fukuda Denshi Co., Ltd., Tokyo, Japan). This device was engineered to record and store SpO2 values continuously, second by second. Initially, in the first phase, SpO2 measurements were taken 30 minutes prior to the 6MWT, which was defined as the 'resting phase'. Subsequently, in the second phase, SpO2 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 SpO2 during the resting phase and the average SpO2 during the 6MWT were measured. ΔSpO2-Ex was defined as the value obtained by subtracting the averaged SpO2 during the 6MWT from the maximum SpO2 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 ΔSpO2-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.