Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease without resting pulmonary hypertension: A systematic review and meta-analysis

Filippo Biondi; Sandra Ghelardoni; Doralisa Morrone; Raffaele De Caterina; Rosalinda Madonna

doi:10.1016/j.vph.2025.107580

Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease without resting pulmonary hypertension: A systematic review and meta-analysis

Vascul Pharmacol. 2026 Mar:162:107580. doi: 10.1016/j.vph.2025.107580. Epub 2026 Jan 20.

Authors

Filippo Biondi¹, Sandra Ghelardoni², Doralisa Morrone¹, Raffaele De Caterina¹, Rosalinda Madonna³

Affiliations

¹ University Cardiology Division, Pisa University Hospital and University of Pisa, Pisa, Italy.
² Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, Pisa, Italy.
³ University Cardiology Division, Pisa University Hospital and University of Pisa, Pisa, Italy. Electronic address: rosalinda.madonna@unipi.it.

PMID: 41570928
DOI: 10.1016/j.vph.2025.107580

Abstract

Exercise pulmonary hypertension (exPH) is currently defined as a mean pulmonary artery pressure to cardiac output slope (mPAP/CO slope) greater than 3 mmHg/L/min during the transition from rest to end-exercise, and a normal mPAP at rest. ExPH may represent an early marker of vascular dysfunction in patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (pH). This is one of the possible complications of pulmonary embolism and is characterized by a variable degree of exercise intolerance. Its natural history is largely unknown and its clinical management is constrained by the lack of validated prognostic markers. We conducted a systematic review and meta-analysis to evaluate the prevalence of exPH and its prognostic role in CTEPD without resting PH. Secondary aims were to ascertain the prevalence of mPAP/CO and PAWP/CO slopes in CTEPD without resting pulmonary hypertension and in patients with post-capillary PH. Upon identification and screening, 12 studies satisfied the criteria for eligibility and were included in the systematic review, with a total of 373 patients. This data base consisted of studies with different designs. Quantitative data were meta-analyzed for each of the aims when provided by at least 5 studies. Approximately 50% of patients suffered from exPH, with a pooled prevalence of 0.50 as per random effect model and 0.44 as per fixed effect model with high heterogeneity. Mean mPAP/CO slope was 4.10 and 3.51 mmHg/L/min as per random effect meta-analysis or common effects model, respectively. The studies included did not provide evidence on the prognostic role in CTEPD without resting PH. Only a few data were reported on PAWP/CO slope and post capillary exPH. In conclusion, our systematic review indicates that ExPH is highly prevalent in CTEPD without resting PH, but its prognostic value is still to be defined.

Keywords: Cardiopulmonary exercise test; Chronic thromboembolic pulmonary disease; Exercise pulmonary hypertension; Stress echocardiography; Ventilation-perfusion scintigraphy.

Publication types

Systematic Review
Meta-Analysis

MeSH terms

Arterial Pressure*
Chronic Disease
Exercise Tolerance*
Exercise*
Female
Humans
Hypertension, Pulmonary* / diagnosis
Hypertension, Pulmonary* / epidemiology
Hypertension, Pulmonary* / physiopathology
Male
Middle Aged
Prevalence
Prognosis
Pulmonary Artery* / physiopathology
Pulmonary Embolism* / diagnosis
Pulmonary Embolism* / epidemiology
Pulmonary Embolism* / physiopathology
Risk Factors