Introduction

Pulmonary hypertension (PH) is a progressive and potentially life-threatening disease characterized by elevated pulmonary arterial pressure, ultimately leading to right ventricular failure and, if left untreated, premature death1. Despite advances in treatment, PH remains associated with high morbidity and mortality, with five-year survival rates ranging from 38% to 57%2,3,4, depending on disease severity. Hospitalization rates are high, with approximately 24.5% of patients requiring PH-related hospitalization within one year5 and many experiencing recurrent admissions6. Hence, early identification of high-risk patients – defined as those with an increased likelihood of clinical deterioration, heart failure hospitalization or mortality – is crucial for optimizing treatment strategies and improving outcomes7.

Detecting high-risk patients early allows clinicians to intervene before advanced right-ventricular dysfunction develops, thereby improving long-term outcomes.

Functional capacity is one of the strongest predictors of mortality in PH8 and current guidelines9 recommend its assessment with the six-minute walk test (6MWT) for risk stratification, as it predicts disease progression and survival in PH patients10,11,12. However, the 6MWT has practical limitations: it is time-consuming, requires a standardized walking course and may not be feasible in primary care settings or resource-limited environments.

The one-minute sit-to-stand test (1-min STST) has been proposed as a simple, reproducible13,14 and cost-effective alternative to the 6MWT15. While the prognostic value of the 1-min STST has been shown in patients with chronic obstructive pulmonary disease (COPD)16 and fibrotic interstitial lung disease17, its utility for predicting long-term adverse outcomes in patients with PH remains uncertain. Recently, 1-min STST cut-offs equivalent to guideline-recommended 6MWT thresholds were published18. In PH patients, the 1-min STST correlates strongly with the 6MWT19,20 and shows comparable associations with validated markers of functional status, disease severity (such as WHO functional class, NT-proBNP and mean pulmonary artery pressure) and quality of life19,21,22, however its ability to correctly identify patients at high risk for long-term adverse outcomes has not been investigated yet.

This study aims to analyze the prognostic value of the 1-min STST for predicting long-term adverse outcomes in patients with PH. Furthermore, it evaluates the utility of previously published 1-min STST cut-offs18 aligned with guideline-recommended 6MWT thresholds for risk stratification.

Methods

Study design and patient population

This prospective cohort study included patients with PH who were consecutively enrolled at the Medical University of Vienna between 2020 and 2024. Eligible participants were adults aged 18 to 90 years with a confirmed diagnosis of PH according to current European PH guidelines9, defined as a mean pulmonary arterial pressure (mPAP) > 20 mmHg measured by right heart catheterization (RHC), who gave their written informed consent.

Patients were excluded if they presented with unstable cardiac conditions (e.g., severe chest pain, acute cardiac decompensation, uncontrolled arrhythmias) at the time of enrollment, or if they had musculoskeletal or neurological impairments (e.g. severe cognitive dysfunction) that could possibly impair their test performance, including the inability to walk or perform sit-to-stand movements.

At baseline, participants underwent a comprehensive evaluation, including demographic and clinical data collection, transthoracic echocardiography, pulmonary function testing and assessment of functional capacity with both, the 1-min STST and the 6MWT. Hemodynamic parameters from RHC were extracted from electronic medical records. Data on long-term outcomes were collected during follow-up.

The study was approved by the ethics committee of the Medical University of Vienna (approval number: 1123/2020) and was conducted in accordance with the principles outlined in the Declaration of Helsinki.

Functional capacity testing

The 1-min STST was performed as previously described23,24. Briefly, patients were instructed to stand up and sit down from a standard chair (seat height: 45 cm) as many times as possible within one minute, without using their arms for support. The total number of complete repetitions was recorded.

The 6MWT was performed indoors on a flat, straight 50-meter walking course, in accordance with American Thoracic Society guidelines25. The test was supervised by trained personnel and each participant received standardized verbal encouragement during the test, as recommended25.

To minimize potential order effects, the two tests were administered in a randomized sequence: 49% of participants performed the 1-min STST first (n = 57) and 51% began with the 6MWT (n = 60). A standardized 15-minute rest interval was implemented between tests, consistent with a previous study26.

Oxygen saturation, heart rate and perceived dyspnea using the modified Borg dyspnea scale (range: 0–10)27 were measured before and after each test.

Outcome assessment and clinical endpoints

The primary endpoint for long-term outcome was defined as a composite of PH-related hospitalizations, transplantations or all-cause mortality. Additionally, all parameters of the composite endpoint were analyzed separately as a secondary endpoint.

PH-related hospitalization was defined as admission due to acute dyspnea, weight gain or peripheral edema requiring intravenous diuretic therapy. Potential hospitalizations were identified via detailed review of medical records by two independent investigators. Discrepancies between reviewers were resolved by consensus discussion, if consensus could not be reached, a third senior investigator adjudicated the case. Mortality data were obtained from institutional records and via the national death registry (“Statistik Austria”).

Follow-up time was calculated from study inclusion until the occurrence of any event or until May 2025, whichever came first.

Statistical analysis

Continuous variables are expressed as mean ± standard deviations (SD) or as median with interquartile range [IQR], depending on their distribution as assessed by the Shapiro Wilk test. Categorical variables are reported as frequencies and percentages.

Patients were stratified into two groups based on the occurrence of adverse events. Group comparisons between patients with and without events were made using the Student’s t-test or the Mann–Whitney U test for continuous variables and the Chi-square test for categorical variables. The correlation between the total number of hospitalizations per patient (as a continuous variable) and 1-min STST performance was assessed using Spearman’s rank correlation coefficient.

Univariable Cox regression was performed to identify predictors of the composite outcome in the overall cohort. To adjust for potential confounding, multivariable Cox regression models with backward selection were applied. To reduce the risk of overfitting from including multiple covariates, three separate multivariable models were constructed: Model 1 included demographics and NT-proBNP, Model 2 included major comorbidities and Model 3 included established PH severity markers.

Patients were stratified into three risk categories based on previously published cut-off values for the 1-min STST18, corresponding to established 6MWT thresholds recommended in current PH guidelines for mortality risk stratification: high-risk (≤ 14 repetitions), intermediate-risk: (15–19 repetitions) and low-risk (≥ 20 repetitions).

Kaplan-Meier survival curves were constructed to compare long-term adverse event rates across these performance risk groups for both the primary and secondary endpoints, with differences assessed using the log-rank test.

All statistical analyses were performed using SPSS version 27 (IBM Corp., Armonk, NY, USA) and R Statistical Software version 4.2.0. A two-sided p-value < 0.05 was considered statistically significant.

Results

Demographic and clinical characteristics

A total of 117 patients with PH were included. The mean age of the participants was 66 ± 14 years and 56% were female. Most patients presented with World Health Organization (WHO) functional class II (35%) or III (50%) symptoms at study inclusion. Median N-terminal pro-brain type natriuretic peptide (NT-proBNP) values were 1001 pg/ml [IQR: 229–2122]. The most prevalent cardiovascular risk factor was arterial hypertension (62%), followed by hyperlipidemia (57%). The mean number of repetitions in the 1-min STST was 17 ± 6.m RHC revealed a mPAP of 41 ± 13 mmHg, a mean pulmonary vascular resistance of 6 ± 4 Wood Units and a mean cardiac index of 2.7 ± 0.6 L/min/m2. Detailed baseline clinical, hemodynamic, echocardiographic and functional characteristics are displayed in Table 1. The distribution of PH subtypes is shown in Supplementary Table S1.

Table 1 Patient characteristics stratified by adverse event status.
Full size table

Comparison by adverse event status

Over a median follow-up of 2.7 years [IQR 1.0–3.9; range: 0.01–5.11 years], 60 patients (51%) had an adverse event, defined by the primary composite endpoint. This included 5 patients (8%) who underwent transplantation (3 double-lung, 2 heart), 42 patients (70%) with ≥ 1 PH-related hospitalization and 13 patients (22%) who died.

Compared to patients without events, those with events were significantly older (70 ± 11 vs. 63 ± 16 years; p = 0.012), had higher NT-proBNP levels (1287 [435–2836] vs. 401 [162–1622] pg/mL; p = 0.002) and more frequently presented in a higher WHO functional class (class III/IV: 70% vs. 40%; p < 0.001). Long-term oxygen therapy was more common in this group (40% vs. 14%; p = 0.002). Cardiovascular risk factors such as smoking (67% vs. 40%; p = 0.004), arterial hypertension (72% vs. 51%; p = 0.021) and hyperlipidemia (67% vs. 47%; p = 0.035) were also more prevalent among patients with adverse events.

Hemodynamically, this group exhibited higher mPAP (44 ± 14 vs. 37 ± 12 mmHg; p = 0.004) and lower mixed venous oxygen saturation (SvO₂, 59 ± 10% vs. 66 ± 7.3%; p < 0.001). Functional capacity was significantly worse in the adverse event group, with lower 6MWT distances (304 ± 126 vs. 402 ± 120 m; p < 0.001) and fewer repetitions in the 1-min STST (15 ± 5.5 vs. 18 ± 7.0 repetitions; p = 0.007). Full comparisons between groups are shown in Table 1.

Based on previously published 1-min STST cut-off values, 41 patients (35%) were categorized as low-risk, 38 (32%) as intermediate-risk and 38 (32%) as high-risk. Interestingly, these cut-offs aligned with tertiles of 1-min STST performance in our cohort.

Association between 1-min STST and long-term outcome

Kaplan–Meier survival analysis revealed a significantly higher incidence of the primary composite outcome among patients in the high-risk 1-min STST group, compared to the intermediate and low-risk groups (log rank p = 0.001; Fig. 1).

Fig. 1
Fig. 1
Full size image

Kaplan-Meier survival curve for the primary composite endpoint stratified by 1-min STST cut-offs.

In univariable Cox regression analysis, age (p = 0.026), NT-proBNP (p < 0.001) and 1-min STST repetitions (p < 0.001) were significant predictors of the primary composite outcome (Fig. 2). Each additional repetition on the 1-min STST was associated with a 6% reduction in the risk of experiencing the composite endpoint (HR per repetition: 0.94; 95% CI: 0.90–0.98; p < 0.001), corresponding to a 27% lower risk for every five additional repetitions (HR: 0.73; 95% CI: 0.60–0.90; p < 0.001).

Fig. 2
Fig. 2
Full size image

Univariable cox regression analysis for the primary composite endpoint. Hazard ratios (HRs) with 95% confidence intervals for individual predictors. A HR < 1.0 indicates a protective effect; HR > 1.0 indicates increased risk. AFib indicates atrial fibrillation; art. HTN, arterial hypertension; BMI, body mass index; CHD, coronary heart disease; comorb, comorbidity; DM, diabetes mellitus; HLP, hyperlipidemia; mPAP, mean pulmonary artery pressure; NTproBNP, N-terminal pro-brain type natriuretic peptide; STST, sit-to-stand test; WHO, World Health Organization.

In multivariable Cox models, 1-min STST performance remained independently associated with long-term adverse outcomes after adjusting for demographic variables and NT-proBNP (Model 1: adjusted HR = 0.95; 95% CI: 0.91–0.99; p = 0.016), as well as after adjusting for key comorbidities (Model 2: adjusted HR = 0.94; 95% CI: 0.90–0.98; p = 0.003). However, statistical significance was lost in Model 3 adjusted for established PH severity markers (p = 0.987; see Table 2).

Table 2 Multivariable cox regression models for the primary composite endpoint using backward selection.
Full size table

Association between 1-min STST and secondary endpoints

Regarding secondary endpoints, 43 patients (37%) were hospitalized at least once. Among them, 23 patients (20%) had ≥ 2 admissions, 11 (10%) ≥ 3 and 5 (4.3%) ≥ 4 admissions. Kaplan-Meier analysis demonstrated significant differences across 1-min STST risk groups for both time to first hospitalization (log rank p = 0.031; Fig. 3A) and time to second hospitalization (log rank p < 0.001; Fig. 3B). Additionally, 1-min STST repetitions correlated inversely with the total number of hospitalizations (Spearman rs = −0.21, p = 0.024).

Fig. 3 
Fig. 3 
Full size image

D. Kaplan-Meier survival curves for secondary endpoints stratified by 1-min STST cut-offs. (A) Time to first PH-related hospitalization (log rank p = 0.031). (B) Time to second PH-related hospitalization (log rank p < 0.001). (C) Time to transplantation (log rank p = not significant). (D) Time to all-cause mortality (log rank p = 0.004).

During the observation period, five patients (4.3%) underwent transplantation after a median of 3.7 years [IQR 2.6–4.1 years]. Transplant-free survival did not significantly differ by 1-min STST performance group based on published cut-offs (log rank p = 0.249; Fig. 3C). Over a median follow-up of 3.4 years [IQR: 1.7–4.7] years, 38 patients (32%) died. The cumulative survival rates at 1, 3, and 5 years were 11% (n = 13), 26% (n = 31) and 32% (n = 38), respectively. Kaplan-Meier analysis demonstrated a significant difference in overall survival across the 1-min STST risk groups (log rank p = 0.004; Fig. 3D), with lower test performance associated with reduced survival.

Discussion

In this study, we explored the prognostic utility of the 1-min STST in patients with PH. Our findings show that the 1-min STST is a significant and independent predictor of long-term adverse outcomes making it a feasible and easy-to-administer tool for assessing functional capacity and long-term mortality risk in PH patients. To the best of our knowledge, this is the first study that investigates the prognostic value of the 1-min STST specifically in PH patients with respect to PH-related hospitalizations, transplantations and long-term mortality.

Consistent with prior studies highlighting the prognostic role of functional capacity in PH28,29, we observed that patients who experienced adverse long-term outcomes had significantly lower performance on both the 6MWT and the 1-min STST. Importantly, the 1-min STST remained a significant predictor of adverse long-term outcomes even after adjustment for demographic factors, and relevant comorbidities including NT-proBNP and age – both well-established predictors of adverse outcomes in PH30,31 – highlighting the test’s value as a complementary prognostic marker.

The diminished prognostic value found in one of our three adjusted models (Model 3), which included established PH severity markers as outlined in current PH guidelines9 and prior studies32,33,34, is likely attributable to multicollinearity, particularly with WHO functional class, as both measures reflect similar aspects of functional capacity. Previous studies have demonstrated strong correlations between the 1-min STST and clinical parameters such as mPAP and WHO functional class19, which may explain the loss of statistical significance when all markers are included simultaneously. Nevertheless, our findings suggest that the 1-min STST is a practical, resource-efficient and informative tool for mortality risk stratification in PH patients, comparable to the 6MWT.

When patients were stratified by established 1-min STST cut-offs18, which aligned with 1-min STST tertiles in our cohort, those in the lowest performance group (≤ 14 repetitions) exhibited significantly highest risk for the primary composite endpoint. This provides further support for the use of the 1-min STST as a prognostic marker in settings where the 6MWT is not feasible. The current findings validate our previously proposed thresholds of 14 and 20 repetitions18 to identify low- and high-risk PH patients, respectively, and confirm their applicability in clinical practice.

Among the secondary endpoints, PH-related hospitalizations, which represent a major clinical and economic burden in PH, were particularly well predicted by the 1-min STST. Patients with fewer repetitions were more likely to experience both first and second hospitalizations and had higher cumulative admission rates, highlighting the test’s potential in identifying patients at risk of repeated hospitalizations – a key metric for healthcare resource planning and patient management.

Our findings align with prior studies suggesting that the STST can serve as a triage tool for care planning in various clinical settings35,36,37, including emergency departments and prehospital care. Its safety and feasibility even in critically ill populations, as shown by prior studies38,39, support our hypothesis of its application for risk stratification even in patients with severe symptoms or disease. Moreover, the test has been proposed as a valuable preoperative screening tool to identify patients at increased risk for postoperative complications in the acute hospital setting following lung transplantations40, providing further evidence of its prognostic value across diverse healthcare settings.

Regarding long-term mortality, another secondary endpoint, our study found significant differences between 1-min STST performance groups, further supporting the clinical value of this test. This is in line with previous findings from Puhan et al., who identified the 1-min STST among others as the best predictor of mortality in patients with COPD. The authors reported an average of 19.5 repetitions in patients alive at 2 years, compared to 11.8 repetitions among those who died16, values closely aligned with our cut-offs of 20 and 14 repetitions. Similarly, Crook et al. confirmed the long-term prognostic value of the test over a five-year follow-up in COPD patients41 and De Buyser et al. likewise reported that lower STST performance predicted increased mortality in older men42. Extending these observations to PH, our findings confirm that reduced performance on the 1-min STST is associated with increased long-term mortality.

Although the 1-min STST did not significantly predict transplantations in our cohort, another secondary endpoint, this is likely due to limited statistical power, as only five transplant events occurred. Additionally, transplantation eligibility is influenced by factors beyond functional capacity, such as organ availability and institutional policies. Nevertheless, prior studies have demonstrated the utility of the 1-min STST in lung transplant candidates43 and its responsiveness to postoperative changes following transplantation44.

Given its simplicity, short duration and minimal logistical requirements, the 1-min STST may serve as a practical alternative to the 6MWT, especially in outpatient clinics, general practitioner offices and resource-limited settings where space or staff constraints may limit the use of longer functional tests. While the 6MWT remains the guideline-recommended9 standard for functional capacity assessment in PH, its implementation can be limited by space, time and personnel constraints. In contrast, the 1-min STST requires minimal equipment and infrastructure, which also reduces healthcare costs, making it a practical alternative. It could be easily digitized or incorporated into mobile health platforms for remote monitoring.

Furthermore, the 1-min STST has demonstrated high reliability and validity in assessing functional capacity in cardiopulmonary populations45,46, including patients with PH22. The previously demonstrated strong correlation between the 1-min STST and the 6MWT19, the routine standard for functional capacity assessment, further supports the use of the 1-min STST as a surrogate measure of functional capacity in PH.

Clinical implications and future directions

The 1-min STST is simple and low-cost, making it especially attractive for routine use in healthcare environments where tests like the 6MWT or cardiopulmonary exercise testing may not be feasible. Its implementation in routine visits could aid in tailoring monitoring intensity and allow clinicians to personalize monitoring intervals and treatment decisions based on individual patient risk profiles. Our findings underscore the broader clinical value of assessing functional capacity in PH. Patients who perform well on physical tests are more likely to maintain independence in daily living and may experience more favorable outcomes overall. Future research should explore the 1-min STST in PH not only as a baseline prognostic tool but also as a longitudinal marker of disease progression and treatment response.

Study limitations

This study has some limitations. First, although we included a wide variety of potential prognostic factors to control for confounding, some important factors may have been omitted (e.g., physical activity, participation in rehabilitation programs).

Second, we excluded participants who failed to complete the 1-min STST and did not group these participants as unable to complete it. Thus, we did not compare participants unable to complete the test with those who were able, which should be investigated in future studies. Third, because our study was conducted in a single center generalizations should be made with caution. However, the single center study-design also offers advantages regarding the consistency of diagnostic work-up, treatment and follow-up and the prospective study design assures consistency and accuracy of the acquired data. Finally, in this study, the 1-min STST and 6MWT were only performed once, without accounting for potential learning effects. While this approach aligns with previous PH studies evaluating the 1-min STST20,47, the impact of repeated 1-min STST testing warrants further investigation.

Conclusion

The 1-min STST is a predictor for long-term adverse outcomes in patients with PH and may serve as a simple and cost-effective tool for risk stratification in this population. Therefore, we postulate that incorporating the 1-min STST into routine clinical assessments of patients with PH as an objective measure may help optimize risk-stratification and improve patient management.