{"doi":"10.1016/j.chest.2025.02.019","title":"Role of Characteristic Pulmonary Impedance With Exercise for Detection of Abnormal Pulmonary Vascular Response and Uncoupling in Pulmonary Hypertension Resulting From Heart Failure With Preserved Ejection Fraction","abstract":"Background Pulmonary hypertension (PH) resulting from heart failure with preserved ejection fraction (PH-HFpEF) can lead to right ventricular-pulmonary arterial (RV-PA) uncoupling despite normal steady hemodynamics (eg, pulmonary vascular resistance). Unsteady hemodynamics, quantified by characteristic pulmonary impedance (Z C ), may be useful in differentiating those patients with PH-HFpEF who have sufficient coupling from those who have insufficient coupling. We hypothesized that abnormal pulsatile hemodynamics with exercise, quantified by Z C , could precisely detect abnormal cardiopulmonary function in PH-HFpEF. Research Question Can Z C with exercise detect abnormal pulmonary vascular response and RV-PA uncoupling in PH-HFpEF? Study Design and Methods Our approach was pilot tested in a small cohort of patients with PH-HFpEF (n = 8), precapillary PH (n = 5), and no PH (n = 2) who underwent rest-exercise (every 25 W)-recovery testing with repeated measurements of characteristic impedance (Z C , from invasive cardiopulmonary exercise and echocardiography for pulmonary vascular pressure-flow) and coupling (end systolic elastance [E es ] to effective arterial elastance [E a ] ratio, from RV pressure-volume loops). Analysis included disease-specific autoregressive correlation structure of order 1 (for repeated measures in time-series analysis). Results Metrics of steady pulmonary hemodynamics with exercise changed in a similar fashion in the 2 disease groups. In contrast, at rest in PH-HFpEF (vs precapillary PH), Z C was low (0.22 [0.14] mm Hg/L/min vs 0.70 [0.20] mm Hg/L/min; P < .0001) and E es to E a ratio was high (1.10 [0.36] vs 0.58 [0.22]; P = .0007). During exercise in PH-HFpEF, Z C increased and E es to E a ratio decreased, but both remained unchanged in precapillary PH. In PH-HFpEF, a significant negative correlation was found between Z C and E es to E a ratio (slope, –0.96; r 2 = 0.18; P < .0001) that was absent in precapillary PH (slope, –0.20; r 2 = 0.11; P = .53). Interpretation Despite the small sample size, RV-PA uncoupling with exercise was significantly negatively correlated with Z C in PH-HFpEF, which was not evident in precapillary PH, suggesting that abnormal exercise pulsatile hemodynamics may be key to RV failure in left-sided heart disease.","journal":"CHEST Journal","year":2025,"id":517121,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":645123,"name":"Farhan Raza","orcid":"0000-0001-5750-2034","position":1,"is_corresponding":false},{"id":795944,"name":"Mitchel J. Colebank","orcid":"0000-0002-2294-9124","position":2,"is_corresponding":false},{"id":507088,"name":"Claudia E. Korcarz","orcid":"0000-0001-9691-9027","position":3,"is_corresponding":false},{"id":323831,"name":"Aimee Teo Broman","orcid":"0000-0003-3783-2807","position":4,"is_corresponding":false},{"id":316489,"name":"Jens C. Eickhoff","orcid":"0000-0003-0525-6462","position":5,"is_corresponding":false},{"id":579427,"name":"Naomi C. Chesler","orcid":"0000-0002-7612-5796","position":6,"is_corresponding":false},{"id":1383407,"name":"Christopher Lechuga","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"40020994","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}