Atrial systole enhances intraventricular filling flow propagation during increasing heart rate

Abstract

Diastolic fluid dynamics in the left ventricle (LV) has been examined in multiple clinical studies for understanding cardiac function in healthy humans and developing diagnostic measures in disease conditions. The question of how intraventricular filling vortex flow pattern is affected by increasing heart rate (HR) is still unanswered. Previous studies on healthy subjects have shown a correlation between increasing HR and diminished E/A ratio of transmitral peak velocities during early filling (E-wave) to atrial systole (A-wave). We hypothesize that with increasing HR under constant E/A ratio, E-wave contribution to intraventricular vortex propagation is diminished. A physiologic in vitro flow phantom consisting of a LV physical model was used for this study. HR was varied across 70, 100 and 120 beats per minute (bpm) with E/A of 1.1–1.2. Intraventricular flow patterns were characterized using 2D particle image velocimetry measured across three parallel longitudinal (apical–basal) planes in the LV. A pair of counter-rotating vortices was observed during E-wave across all HRs. With increasing HR, diminished vortex propagation occurred during E-wave and atrial systole was found to amplify secondary vorticity production. The diastolic time point where peak vortex circulation occurred was delayed with increasing HR, with peak circulation for 120 bpm occurring as late as 90% into diastole near the end of A-wave. The role of atrial systole is elevated for higher HR due to the limited time available for filling. Our baseline findings and analysis approach can be applied to studies of clinical conditions where impaired exercise tolerance is observed.

Introduction

Intraventricular vortex formation during diastole has been examined in multiple studies for providing insight into normal cardiac function and also for diagnostic purposes in diseases such as dilated cardiomyopathy, diastolic dysfunction (DDF) and heart failure with normal ejection fraction (HFNEF) (Eriksson et al., 2011, Gharib et al., 2006, Ghosh et al., 2014, Hendabadi et al., 2013, Kheradvar et al., 2012, Le and Sotiropoulos, 2013, Pedrizzetti et al., 2014, Pedrizzetti et al., 2015, Seo et al., 2014, Stewart et al., 2012). A baseline understanding of exercise hemodynamics for healthy conditions is needed prior to comparison with pathological conditions such as DDF and HFNEF where exercise intolerance is observed (O׳Rourke, 2001, Udelson, 2011). The paradigm of intraventricular vortex characterization can be extended for studies of exercise physiology. While hemodynamic characteristics such as pressures, ejection fraction, E/A ratio and E/E^′ ratio have been examined under increasing heart rate (HR) for healthy volunteers (Iliceto et al., 1991, Swinne et al., 1992, Yamamoto et al., 1993), no study to date has examined the alterations in intraventricular filling flow patterns under increased HR. This latter point is the subject of the current study.

We use physical modeling to address a basic but unanswered question: how does increasing HR impact intraventricular filling when E/A ratio and systemic pressure are maintained constant? Though the latter assumptions are not truly reflective of the hemodynamic alterations that typically occur during exercise (increased SV, pulse pressure and E/A ratio), we underscore that our current effort is the starting point to tackle a complex physiological scenario in a systematic manner. Clinical studies of exercise hemodynamics under increasing HR are challenged in their ability to provide mechanistic explanations for functional observations, mainly due to highly interrelated nature of the underlying physiological variables (e.g., age, sex, systemic pressure, SV, LV stiffness, pulmonary venous flow, venous return). Physical models such as what was used in this study can provide a powerful means to examine the isolated mechanistic impact of select variables on specific hemodynamic and functional outcomes in physiological studies.

We hypothesize that with increasing HR under constant E/A ratio, the contribution of the E-wave to the propagation of intraventricular filling flow is diminished. We expect this based on the limited overall diastolic duration with increasing HR. We tested the hypothesis using an in vitro LV phantom model. The rationale for maintaining a constant E/A across all conditions was to identify if there were any changes in intraventricular flow simply due to increasing HR, even when contribution of atrial systole (hereon referred to as A-wave) relative to early diastolic filling (hereon referred to as E-wave) remains unaltered from resting condition.