Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study

Abstract

Leite S, Oliveira-Pinto J, Tavares-Silva M, Abdellatif M, Fontoura D, Falcão-Pires I, Leite-Moreira AF, Lourenço AP. Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study. Am J Physiol Heart Circ Physiol 308: H1556 -H1563, 2015. First published April 11, 2015; doi:10.1152/ajpheart.00076.2015.-Inclusion of exercise testing in diagnostic guidelines for heart failure with preserved ejection fraction (HFpEF) has been advocated, but the target population, technical challenges, and underlying pathophysiological complexity raise difficulties to implementation. Hemodynamic stress tests may be feasible alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old WistarKyoto, ZSF1 lean, and obese rats (n ϭ 7 each) randomly and sequentially underwent (crossover) Trendelenburg (30°), 5 g·Kg Ϫ1 ·min Ϫ1 dobutamine, and 7.5 g·Kg Ϫ1 ·min Ϫ1 phenylephrine with simultaneous left ventricular (LV) pressure-volume loop and echocardiography evaluation under halogenate anesthesia. Effort testing with maximum O2 consumption (V O2 max) determination was performed 1 wk later. Obese ZSF1 showed lower effort tolerance and V O2 max along with higher resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas dobutamine decreased it. Significant correlations were found between EDP and 1) peak early filling Doppler velocity of transmitral flow (E) to corresponding myocardial tissue Doppler velocity (E=) ratio, 2) E to E-wave deceleration time (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by receiver-operating characteristic curve analysis for elevation of EDP above a cut-off of 13 mmHg during hemodynamic stress was high (area under curve, AUC ϭ 0.95) but not higher than that of E/E= (AUC ϭ 0.77, P ϭ 0.15). Results in ZSF1 obese rats suggest that noninvasive echocardiography after hemodynamic stress induced by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and constitute an alternative to effort testing. heart failure with preserved

Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

“…Despite preserved systolic function, hypertensive, obese, and diabetic ZSF1 obese rats (ZSF1 Ob) show high end-diastolic pressure (EDP) and increased cardiomyocyte stiffness that can be ascribed mostly to titin hypophosphorylation (9). Moreover, these animals show impaired maximal oxygen consumption (V O 2 max ) and decreased anaerobic threshold in effort testing and low diastolic function tolerance to both afterload and preload closely mimicking clinical HFpEF (20). Indeed, many patients who have high passive stiffness may not show symptoms at rest.…”

Spectral transfer function analysis of respiratory hemodynamic fluctuations predicts end-diastolic stiffness in preserved ejection fraction heart failure

“…We applied PSD and STF analysis to beat-to-beat fluctuations induced by ventilation in EDP, EDV i , and SV i in the robust ZSF1 obese rat model of metabolic syndrome and HFpEF that we recently described (12,22) documenting elevation of EDP PSD, impaired STF gain between EDP and SV i and enhanced STF gain between EDV i and EDP in experimental HFpEF but not in hypertensive or healthy controls. STF gain impairment from EDP to SV i was independently correlated with end-diastolic stiffness as assessed by the EDPVR and showed good diagnostic performance in discriminating elevated end-diastolic stiffness supporting the use of STF gain analysis of respiratory fluctuations in LV filling pressure and SV or any noninvasive surrogate of these as a means to screen or diagnose HFpEF.…”

“…We have previously described the ZSF1 obese rat metabolic syndrome model as a good model of HFpEF. Indeed, ZSF1 obese rats show myocardial hypertrophy, elevated LV filling pressures, upward-shifted EDPVR, increased myocardial stiffness and myofilament derangements involved in the pathophysiology of HFpEF (12), along with lung congestion, effort intolerance, and impaired maximum oxygen consumption (V O 2 max ) thereby closely mimicking HFpEF (22). Standard measures of contractility are preserved or even suggest a hypercontractile phenotype.…”

“…ZSF1 obese (ZSF1 Ob, n ϭ 14), ZSF1 lean (ZSF1 Ln, n ϭ 14) and Wistar-Kyoto rats (WKY, n ϭ 14; Charles River Laboratories, Barcelona, Spain) were fed with standard diet (Purina diet 5008) to achieve metabolic syndrome and HFpEF, systemic arterial hypertension, or absence of any cardiovascular risk factor, respectively, as previously reported (12,22). Animals were kept in individually ventilated chambers, in groups of two per cage under controlled environment with a 12:12-h light-dark cycle at 22°C room temperature.…”

“…For this purpose we performed spectral and STF analysis of beat-tobeat hemodynamic parameters during ventilation in both openchest (OC) and closed-chest conditions (CC) in the ZSF1 obese rat model of metabolic syndrome and cardiometabolic riskrelated HFpEF, a model that we newly characterized (12,22). Finally we tested the possibility that the gain of STF between end-diastolic pressure (EDP) and SV was mainly related with end-diastolic stiffness and could be used as a screening or diagnostic tool.…”