Abstract
Background: Passive leg lifting (PLL) may serve as a simple alternative to simulate exercise stress.
Methods and Results: We evaluated 33 patients with PH who underwent PLL-RHC and exercise right heart catheterization (RHC); 25 patients were classified as having PLL-induced PH (LIPH), demonstrating significant increases in mean pulmonary arterial pressure (mPAP) and mPAP–cardiac output slopes. Strong correlations were observed between PLL-RHC and exercise RHC measurements.
Conclusions: PLL-RHC may represent a simple method for detecting EIPH.
Central Figure
Pulmonary hypertension (PH) is a serious disease, but early detection improves prognosis.1 Stress testing is very important in various heart diseases and PH.2 Exercise-induced PH (EIPH) is recognized as an early manifestation of pulmonary vascular disease. Although right heart catheterization (RHC) during supine exercise remains the gold standard for EIPH, it requires specialized equipment and patient cooperation. In many settings, particularly with older or frail patients, exercise RHC may not be feasible.
Passive leg lifting (PLL) increases venous return, augmenting cardiac preload by shifting blood volume centrally. Although frequently used to assess fluid responsiveness, its potential to mimic exercise has not been validated for the diagnosis of EIPH. This study evaluated the utility of PLL as a diagnostic surrogate for exercise RHC by comparing hemodynamic parameters during PLL with those from conventional supine exercise testing in patients with suspected EIPH.
We retrospectively analyzed 33 patients with suspected EIPH who underwent PLL-RHC and exercise RHC at our institution between May 2022 and August 2023. All patients had a resting mean pulmonary arterial pressure (mPAP) <25 mmHg and were classified as World Health Organization functional class I or II. Patients with left heart disease (pulmonary artery wedge pressure>15 mmHg) were excluded.
PLL was performed by elevating both legs to 45 degrees for 3 min while patients remained supine in ambient air. Hemodynamic measurements, including mPAP and cardiac output (CO), were recorded at baseline and after PLL. The mPAP–CO slope was calculated as the change in mPAP divided by the change in CO. PLL-induced PH (LIPH) was defined as an mPAP–CO slope >3.0 mmHg/L/min.
Following PLL, patients underwent exercise RHC using a supine cycle ergometer. The protocol began at 20 W and increased by 10 W every 2 min up to a maximum of 70 W, with continuous hemodynamic monitoring. EIPH was defined as an exercise mPAP–CO slope >3.0 mmHg/L/min, consistent with updated ESC/ERS guidelines.
Among the 33 patients (mean age 63±13 years; 48% male), 25 (76%) met the criteria for LIPH, whereas 8 were classified as non-LIPH (Table). Baseline hemodynamic variables, including mPAP and CO, did not differ significantly between groups. However, after PLL, the LIPH group exhibited a significantly greater increase in mPAP (∆mPAP) and a steeper mPAP–CO slope compared to the non-LIPH group (9.2±1.1 vs. 1.7±0.4 mmHg/L/min; P=0.003). Similar trends were observed during exercise testing (mPAP–CO slope: 4.4±0.4 vs. 1.9±0.4 mmHg/L/min; P=0.002).
Table.
Baseline Characteristics of the Patients
| Category |
Non-LIPH group
(n=8) |
LIPH group
(n=25) |
P value |
| Age (years) |
57±4 |
64±3 |
0.18 |
| Sex, male, n (%) |
5 (62.5) |
11 (44.0) |
0.44 |
| Body weight (kg) |
67.8±6.3 |
62.3±2.7 |
0.36 |
| Body mass index (kg/m2) |
24.3±1.5 |
24.4±0.7 |
0.96 |
| Background disease |
| CTEPH |
7 (87.5) |
22 (88.0) |
1 |
| History |
| Diabetes mellitus, n (%) |
2 (25) |
0 |
– |
| Hyperlipidemia, n (%) |
6 (75) |
13 (52) |
0.42 |
| Hypertension, n (%) |
3 (37.5) |
11 (44) |
1 |
| Medications |
| Diuretics, n (%) |
4 (50) |
12 (48) |
1 |
| Anti-pulmonary hypertension drugs |
7 (87) |
18 (72) |
0.34 |
| Laboratory tests |
| B-type natriuretic peptide level (pg/mL) |
11.7±2.3 |
18.0±3.2 |
0.26 |
| Hemoglobin level (g/dL) |
13.4±0.4 |
12.5±0.2 |
0.1 |
| Echocardiography variables |
| Ejection fraction (%) |
68.8±0.8 |
68.7±1.3 |
0.99 |
| TRPG (mmHg) |
20.8±1.9 |
22.3±1.5 |
0.58 |
| TAPSE (mm) |
21.4±1.1 |
21.0±0.6 |
0.75 |
| Fractional area change (%) |
42.9±1.4 |
42.8±0.9 |
0.98 |
| 6-minute walk time |
| 6-minute walk distance (m) |
592±39 |
515±27 |
0.14 |
| Right heart catheterization at rest |
| Heart rate (beats/min) |
63±4 |
62±2 |
0.8 |
| Systolic blood pressure (mmHg) |
115±4 |
119±4 |
0.52 |
| Diastolic blood pressure (mmHg) |
74±3 |
67±2 |
0.15 |
| Mean blood pressure (mmHg) |
89±4 |
82±2 |
0.15 |
| Right arterial pressure (mmHg) |
4.8±0.5 |
4.7±0.4 |
0.92 |
| PAWP (mmHg) |
7.1±0.6 |
8.4±0.5 |
0.12 |
| Systolic PAP (mmHg) |
23.9±1.9 |
26.3±1.0 |
0.23 |
| Diastolic PAP (mmHg) |
11.5±1.2 |
11.3±0.5 |
0.87 |
| Mean PAP (mmHg) |
17.0±1.1 |
17.7±0.6 |
0.58 |
| Cardiac output (L/min) |
5.04±0.22 |
4.37±0.20 |
0.08 |
| Pulmonary vascular resistance (Wood units) |
1.93±0.20 |
2.20±0.18 |
0.43 |
| PaO2 (mmHg) |
80.3±4.9 |
79.3±1.8 |
0.81 |
| PaCO2 (mmHg) |
39.0±1.6 |
40.2±0.8 |
0.47 |
| SaO2 (%) |
94.8±0.7 |
94.8±0.4 |
0.94 |
| SaCO2 (%) |
73.1±0.9 |
71.2±1.0 |
0.29 |
| Right heart catheterization at leg lifting |
| Heart rate (beats/min) |
72±4 |
69±3 |
0.67 |
| Systolic blood pressure (mmHg) |
121±8 |
124±3 |
0.69 |
| Diastolic blood pressure (mmHg) |
76±2 |
71±2 |
0.28 |
| Mean blood pressure (mmHg) |
90±3 |
87±2 |
0.52 |
| Systolic PAP (mmHg) |
27.0±1.0 |
34.5±1.6 |
0.01 |
| Diastolic PAP (mmHg) |
12.9±0.8 |
15.3±0.7 |
0.08 |
| mPAP (mmHg) |
19.1±0.8 |
23.2±0.9 |
0.02 |
| Cardiac output (L/min) |
6.01±0.20 |
5.05±0.23 |
0.04 |
| mPAP-CO slope (mmHg/L/min) |
1.73±0.39 |
9.17±1.07 |
0.003 |
| Right heart catheterization at exercise |
| Maximum workload (W) |
68±3 |
66±2 |
0.71 |
| Heart rate (beats/min) |
113±6 |
108±3 |
0.42 |
| Systolic blood pressure (mmHg) |
147±5 |
151±6 |
0.69 |
| Diastolic blood pressure (mmHg) |
103±3 |
108±33 |
0.39 |
| Mean blood pressure (mmHg) |
89±4 |
82±2 |
0.15 |
| PAWP (mmHg) |
13.8±2.2 |
17.6±1.6 |
0.21 |
| Systolic PAP (mmHg) |
38.8±3.0 |
53.3±2.7 |
0.01 |
| Diastolic PAP (mmHg) |
18.5±1.4 |
25.1±1.4 |
0.02 |
| mPAP (mmHg) |
28.8±2.0 |
39.0±1.8 |
0.01 |
| Cardiac output (L/min) |
11.6±0.9 |
9.44±0.40 |
0.02 |
| mPAP-CO slope (mmHg/L/min) |
1.91±0.42 |
4.35±0.40 |
0.002 |
| Borg scale score |
14.3±0.7 |
14.7±0.6 |
0.69 |
Values are shown as mean±standard error of the mean (SEM). Unpaired t-test. CTEPH, chronic thromboembolic pulmonary hypertension; LIPH, passive leg lifting-induced pulmonary hypertension; PaCO2, partial pressure of arterial carbon dioxide; PaO2, partial pressure of arterial oxygen; PAP, pulmonary arterial pressure; PAWP, pulmonary artery wedge pressure; SaO2, oxygen saturation in arterial blood; SvO2, oxygen saturation in the pulmonary artery; TAPSE, tricuspid annual plane systolic excursion; TRPG, tricuspid regurgitation pressure gradient.
Of the 25 patients with LIPH, 18 (72%) were also diagnosed with EIPH, yielding a positive predictive value of 0.72. Conversely, only 1 of the 8 non-LIPH patients had EIPH, resulting in a negative predictive value of 0.88. A significant correlation was observed between PLL-derived and exercise-derived mPAP–CO slopes (P=0.005). Receiver operating characteristic (ROC) curve analysis demonstrated that a ∆mPAP ≥4.0 mmHg during PLL had a sensitivity of 100% and a specificity of 36% for predicting EIPH (AUC=0.88, P<0.001). An mPAP–CO slope ≥3.04 mmHg/L/min yielded an AUC of 0.77, with a sensitivity of 87.5% and a specificity of 56.5%.
Our findings support the feasibility and clinical relevance of PLL as a non-exercise stress test during RHC for detecting EIPH. PLL-RHC showed good concordance with exercise RHC and strong predictive value for EIPH. The physiological basis of PLL involves a transient increase in venous return and preload, leading to elevated cardiac filling pressures and pulmonary changes that may unmask latent dysfunction. No adverse events were observed.
Given its simplicity, low cost, and broad applicability, PLL may be valuable in older patients who are unable to perform exercise testing. Although previous studies have evaluated fluid challenges or pharmacologic provocation, PLL offers a purely mechanical, bedside-friendly alternative that can be easily standardized. The mPAP–CO slope during PLL showed a substantial increase. However, the maneuver may be more preload-dependent and influenced by variable venous return than standardized exercise. The clinical implications are meaningful. Although definitive evidence for early intervention in mild PH is limited, early detection may allow closer follow-up and timely reassessment if symptoms worsen. It may help assess residual pulmonary vascular disease after therapy for conditions such as chronic thromboembolic PH(CTEPH).
In conclusion, PLL-RHC may serve as a simple, noninvasive, and informative alternative to exercise testing for the detection of EIPH. In selected patients, particularly those for whom exercise testing is not feasible, PLL-RHC can provide valuable diagnostic insights and inform management decisions. Future prospective studies are warranted to validate its prognostic significance and assess its role in early PH screening strategies.
Disclosures
F.O. is a member of Circulation Journal’s Editorial Team.
IRB Information
Name of the ethics committee: the Ethics Committee of Yokohama City University Hospital: Reference number: F230500041.
References
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Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022; 43: 3618–3731.
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Kitai T, Kohsaka S, Kato T, Kato E, Sato K, Teramoto K, et al. JCS/JHFS 2025 Guideline on diagnosis and treatment of heart failure. Circ J 2025; 89: 1278–1444.
