Abstract

BackgroundIntraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. Although, systolic gradients have also been observed, data are lacking on their magnitude and modulation during cardiac dysfunction. Furthermore, we know that segmental dysfunction interferes with the normal sequence of regional contraction and might be expected to alter the physiological intraventricular pressure gradients. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis.Methods/DesignAnimal Studies: Six rabbits will be completely instrumented to measuring apex to outflow-tract pressure gradient and apical and basal myocardial segments lengthening changes at basal, afterloaded and ischemic conditions. Afterload increase will be performed by abruptly narrowing or occluding the ascending aorta during the diastole and myocardial ischemia will be induced by left coronary artery ligation, after the first diagonal branch.Patient Studies: Patients between 65-80 years old (n = 12), both genders, with severe aortic stenosis referred for aortic valve replacement will be selected as eligible subjects. A high-fidelity pressure-volume catheter will be positioned through the ascending aorta across the aortic valve to measure apical and outflow-tract pressure before and after aortic valve replacement with a bioprosthesis. Peak and average intraventricular pressure gradients will be recorded as apical minus outflow-tract pressure and calculated during all diastolic and systolic phases of cardiac cycle.DiscussionWe expect to validate the application of our method to obtain intraventricular pressure gradients in animals and patients and to promote a methodology to better understand the ventricular relaxation and filling and their correlation with systolic function.

Highlights

  • Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement

  • Normal diastolic function of the left ventricle (LV) can be defined as the ability of the ventricle to adequately fill under low filling pressures

  • Patient studies 1) Validate the invasive measurement of intraventricular pressure gradients (IVPG) for systolic and diastolic function evaluation in patients with severe aortic stenosis (AS); 2) Apply this methodology to evaluate whether the IVPG improve in AS patients immediately after aortic valve replacement (AVR); 3) Establish if IVPG changes correlate with the reduction in LV obstruction and improvement in LV function; 4) Correlate catheter measurements with preoperative echocardiography; 5) Evaluate the potential clinical applicability of the concepts derived from the experimental studies

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Summary

Introduction

Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis. As early as 1930, Katz [4] already speculated that diastole was not entirely a passive process and the LV had the ability to “exert a sucking action to draw blood into its chamber.” It was only in 1979 that Ling et al [5] first described, in a canine model, intraventricular pressure gradients (IVPG) during relaxation and filling of the LV. When Nikolic et al [8] in 1995 demonstrated IVPG during early diastole in filling as well as in non-filling heart beats, the hope that IVPG would become an index for isovolumic and early ventricular relaxation was substantiated

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