title: Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.
abstract: Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP) <25 mmHg at rest in patients that remain symptomatic from chronic pulmonary artery thrombi. To improve identification of right ventricular (RV) pathology in patients with thromboembolic obstruction, we hypothesized that the RV ventriculo-arterial (Ees/Ea) coupling ratio at maximal stroke work (Ees/Eamax sw) derived from an animal model of pulmonary obstruction may be used to identify occult RV dysfunction (low Ees/Ea) or residual RV energetic reserve (high Ees/Ea). Eighteen open chested pigs had conductance catheter RV pressure-volume (PV)-loops recorded during PA snare to determine Ees/Eamax swThis was then applied to 10 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and ten patients with CTED, also assessed by RV conductance catheter and cardiopulmonary exercise testing. All patients were then restratified by Ees/Ea. The animal model determined an Ees/Eamax sw= 0.68 ± 0.23 threshold, either side of which cardiac output and RV stroke work fell. Two patients with CTED were identified with an Ees/Ea well below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea ≥ 0.68 suggesting residual RV energetic reserve. Ees/Ea > 0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively,P= 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively,P< 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction.
authors.affiliation: Medical Physics and Clinical Engineering, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.|Postgraduate Medical Institute, Anglia Ruskin University, Chelmsford, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Axell
authors.affiliation: Department of Cardiovascular Surgery, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Messer
authors.affiliation: Medical Physics and Clinical Engineering, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.|Postgraduate Medical Institute, Anglia Ruskin University, Chelmsford, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: White
authors.affiliation: Pulmonary Vascular Diseases Unit, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Colm
authors.initials: C
authors.lastname: McCabe
authors.affiliation: Medical Physics and Clinical Engineering, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Priest
authors.affiliation: The Royal Veterinary College, Hatfield, London, UK.
authors.forename: Thaleia
authors.initials: T
authors.lastname: Statopoulou
authors.affiliation: The Royal Veterinary College, Hatfield, London, UK.
authors.forename: Maja
authors.initials: M
authors.lastname: Drozdzynska
authors.affiliation: The Royal Veterinary College, Hatfield, London, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Viscasillas
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Hinchy
authors.affiliation: Postgraduate Medical Institute, Anglia Ruskin University, Chelmsford, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hampton-Till
authors.affiliation: The Royal Veterinary College, Hatfield, London, UK.
authors.forename: Hatim I
authors.initials: HI
authors.lastname: Alibhai
authors.affiliation: Pulmonary Vascular Diseases Unit, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Morrell
authors.affiliation: Pulmonary Vascular Diseases Unit, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pepke-Zaba
authors.affiliation: Department of Cardiovascular Surgery, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Large
authors.affiliation: Department of Interventional Cardiology, Papworth Hospital NHS Foundation Trust, Cambridge, UK s.hoole@nhs.net.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hoole
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000502:physiology*; D011655:Pulmonary Embolism / Q000503:physiopathology*; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*
keywords: Chronic thromboembolic disease; chronic thromboembolic pulmonary hypertension; right ventricular dysfunction; ventriculo‐arterial coupling