title: Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function.
abstract: In cardiovascular research, relaxation and stiffness are calculated from pressure-volume (PV) curves by separately fitting the data during the isovolumic and end-diastolic phases (end-diastolic PV relationship), respectively. This method is limited because it assumes uncoupled active and passive properties during these phases, it penalizes statistical power, and it cannot account for elastic restoring forces. We aimed to improve this analysis by implementing a method based on global optimization of all PV diastolic data. In 1,000 Monte Carlo experiments, the optimization algorithm recovered entered parameters of diastolic properties below and above the equilibrium volume (intraclass correlation coefficients = 0.99). Inotropic modulation experiments in 26 pigs modified passive pressure generated by restoring forces due to changes in the operative and/or equilibrium volumes. Volume overload and coronary microembolization caused incomplete relaxation at end diastole (active pressure > 0.5 mmHg), rendering the end-diastolic PV relationship method ill-posed. In 28 patients undergoing PV cardiac catheterization, the new algorithm reduced the confidence intervals of stiffness parameters by one-fifth. The Jacobian matrix allowed visualizing the contribution of each property to instantaneous diastolic pressure on a per-patient basis. The algorithm allowed estimating stiffness from single-beat PV data (derivative of left ventricular pressure with respect to volume at end-diastolic volume intraclass correlation coefficient = 0.65, error = 0.07 ± 0.24 mmHg/ml). Thus, in clinical and preclinical research, global optimization algorithms provide the most complete, accurate, and reproducible assessment of global left ventricular diastolic chamber properties from PV data. Using global optimization, we were able to fully uncouple relaxation and passive PV curves for the first time in the intact heart.
authors.affiliation: Department of Cardiology, Hospital General Universitario Gregorio Marañón, and the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. javbermejo@jet.es
authors.forename: Javier
authors.initials: J
authors.lastname: Bermejo
authors.forename: Raquel
authors.initials: R
authors.lastname: Yotti
authors.forename: Candelas
authors.initials: C
authors.lastname: Pérez del Villar
authors.forename: Juan C
authors.initials: JC
authors.lastname: del Álamo
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodríguez-Pérez
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Legazpi
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benito
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Antoranz
authors.forename: M Mar
authors.initials: MM
authors.lastname: Desco
authors.forename: Ana
authors.initials: A
authors.lastname: González-Mansilla
authors.forename: Alicia
authors.initials: A
authors.lastname: Barrio
authors.forename: Jaime
authors.initials: J
authors.lastname: Elízaga
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández-Avilés
mesh_terms: D000465:Algorithms; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D006328:Cardiac Catheterization / Q000379:methods; D002306:Cardiac Volume / Q000502:physiology; D003971:Diastole / Q000502:physiology*; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D013318:Stroke Volume / Q000502:physiology; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: diastole; diastolic function; diastolic stiffness; hemodynamics; left ventricle; mechanical properties; pressure; relaxation