Normal limits for the right ventricle-pulmonary circulation exercise echocardiography: a meta-analysis.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Healthy subjects (n=1122). Intervention: Exercise Doppler echocardiography. Primary outcome: Pooled mean estimates and lower/upper limits of normal (5th and 95th percentiles) for exercise echocardiography measurements (TRV, sPAP, mPAP, mPAP/CO slope, E/e', TAPSE, TAPSE/sPAP).

Q: What does this research mean for the field?

In healthy adults undergoing exercise echocardiography, the upper limits of normal are 57.8 mmHg for sPAP, 43.0 mmHg for mPAP, and 3.0 mmHg·min·L−1 for mPAP/CO slope, while the lower limit of normal for TAPSE/sPAP is 0.4 mm·mmHg−1. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Francesco Ferrara; Valentina Capone; Monica Franzese; Andreina Carbone; Erberto Carluccio; Rosanna Castaldo; Rodolfo Citro; Antonio Cittadini; Anna Grazia D'Agostino; Michele D’Alto; Andrea Esposito; Giovanni Esposito; Luna Gargani; Stefano Ghio; Graziella Lacava; Alberto Maria Marra; Ciro Mauro; Emanuela Passaro; Salvatore Rega; Andrea Soricelli; Ekkehard Grünig; Robert Naeije; Eduardo Bossone

doi:10.1183/16000617.0188-2025

Key result

Exercise Doppler echocardiography defines reference limits for pulmonary hemodynamics, setting mPAP/CO slope upper normal at ~3.0.

n=1,122

Why the study?

Normal limits for exercise Doppler echocardiography measurements of the right ventricle, pulmonary artery, and left atrial unit remain inadequately defined.

What are the normal reference limits for right ventricle and pulmonary circulation parameters measured by exercise Doppler echocardiography in healthy subjects?

Key Points

To establish normal reference limits for exercise Doppler echocardiography measurements evaluating the right ventricle, pulmonary artery, and left atrial unit in healthy individuals.
Searched Medline, Web of Science, and Scopus (1999–2024) for exercise Doppler echocardiography studies using supine or semi-recumbent cycle ergometers in healthy subjects.
Calculated pooled summary mean estimates using a restricted maximum-likelihood random-effects model, defining lower and upper limits of normal as the 5th and 95th percentiles.
Analyzed data across 19 eligible studies comprising 1122 healthy subjects with a mean±sd age of 42.8±18.3 years.
Peak exercise pulmonary pressure metrics showed a pooled mean sPAP of 38.5 mmHg (upper limit of normal 57.8 mmHg; range 18.8–57.8 mmHg) and mPAP of 29.8 mmHg (upper limit of normal 43.0 mmHg; range 16.2–43.0 mmHg).
During exercise, pooled mean TRV reached 2.5 m·s−1 (upper limit of normal 3.4 m·s−1), and the mPAP/CO slope averaged 1.4 mmHg·min·L−1 with an upper limit of normal of 3.0 mmHg·min·L−1.
Right ventricular functional metrics during exercise showed a pooled mean TAPSE of 31.8 mm (lower limit of normal 24.6 mm) and a mean TAPSE/sPAP ratio of 0.8 mm·mmHg−1 (lower limit of normal 0.4 mm·mmHg−1).

Study Design

Type

Meta-Analysis (n=1,122)

Multicenter

Yes

Structured PICO

What are the normal reference limits for right ventricle and pulmonary circulation parameters measured by exercise Doppler echocardiography in healthy subjects?

P

Population

1,122 healthy adult subjects (mean age 42.8 years) pooled from 19 studies undergoing supine or semi-recumbent cycle ergometer exercise echocardiography to establish normal reference limits.

E

Exposure

Exercise Doppler echocardiography (ex-TTE) using a graded semi-supine or semi-recumbent cycle ergometer protocol up to symptom-limited maximal exercise

O

Outcome

Pooled mean estimates and lower and upper limits of normal (defined as 5th and 95th percentiles) for right ventricle, pulmonary artery, and left atrial unit measurements during exercisesurrogate

Establishing robust noninvasive reference limits for right ventricular and pulmonary hemodynamic response to exercise enables better identification of latent cardiorespiratory diseases.

Limitations

Substantial heterogeneity observed across included studies, possibly reflecting differences in expertise or demographics.
Fewer than 10 studies for most parameters prevented meta-regression for age dependency.
Methodological limitations in estimating PAWP during high levels of exercise due to fusion of E and A waves.
Wide range of normal values for TAPSE/sPAP ratio may limit individual patient-level decision-making.
Incomplete reporting of variables precluded formal missing data assessment.
Significant between-study heterogeneity for several parameters.
Inability to perform meta-regression for age-dependency due to small number of studies.
PAWP estimation from E/e' is technically challenging during moderate to maximal exercise.
Incomplete data reporting across studies prevented analysis of missing data.

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Implication

These reference limits enable standardized interpretation of exercise echocardiography; extends prior data via pooled healthy-subject estimates.

Abstract

Normal limits for exercise Doppler echocardiography (ex-TTE) measurements of the right ventricle (RV), pulmonary artery (PA) and left atrial (LA) unit remain inadequately defined. This meta-analysis aims to establish normal limits for measurements of the RV-PA-LA unit. A comprehensive literature search of Medline, Web of Science and Scopus (1 January 1999–December 2024) was performed. We included ex-TTE studies performed using a supine/semi-recumbent cycle ergometer in healthy subjects that reported the following parameters: tricuspid regurgitation velocity (TRV), systolic pulmonary artery pressure (sPAP), mean pulmonary artery pressure (mPAP), mPAP/cardiac output (CO) slope, mitral Doppler E to tissue Doppler e′ ratio (E/e′), tricuspid annular plane excursion (TAPSE) and TAPSE/sPAP. Summary mean estimates were calculated using a restricted maximum-likelihood random-effects model. Lower and upper limits of normal (LLN and ULN) were defined as the 5th and 95th percentiles. Between-study heterogeneity was assessed using the Q-statistic and quantified with the inconsistency index. Data on 1122 healthy subjects (mean±sd age: 42.8±18.3 years) across 19 eligible studies were analysed. The pooled mean estimates and limits of normal for ex-TTE measurements were as follows: TRV 2.5 m·s−1 (ULN 3.4), sPAP 38.5 mmHg (ULN 57.8), mPAP 29.8 mmHg (ULN 43.0), mPAP/CO slope 1.4 mmHg·min·L−1 (ULN 3.0), E/e′ 7.1 (ULN 11.5), TAPSE 31.8 mm (LLN 24.6), TAPSE/sPAP 0.8 mm·mmHg−1 (LLN 0.4). Despite notable heterogeneity for several measurements, the present meta-analysis provides a robust framework for defining normal reference limits for ex-TTE measurements of the RV-PA-LA unit. Shareable abstract Normal limits for exercise echocardiography (ex-TTE) of the right ventricle (RV) and pulmonary circulation (PC) need to be better defined. The present meta-analysis provides a robust framework for defining RV-PC ex-TTE normal reference limits. https://bit.ly/4cWmHQh

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Cite This Study

Ferrara et al. (2026) conducted a meta-analysis in Healthy subjects (n=1,122). Exercise Doppler echocardiography was evaluated on Pooled mean estimates and lower/upper limits of normal (5th and 95th percentiles) for exercise echocardiography measurements (TRV, sPAP, mPAP, mPAP/CO slope, E/e', TAPSE, TAPSE/sPAP). Exercise Doppler echocardiography established normal limits for pulmonary circulation, including an upper limit of normal for mPAP/CO slope of 3.0 mmHg·min·L−1 and a lower limit for TAPSE of 24.6 mm.

synapsesocial.com/papers/6ad0fc7415427f6a840401ae https://doi.org/10.1183/16000617.0188-2025

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Normal limits for the right ventricle-pulmonary circulation exercise echocardiography: a meta-analysis.

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Normal limits for the right ventricle-pulmonary circulation exercise echocardiography: a meta-analysis.

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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