A.H.M. Jansen

Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates (n = 19) and in healthy control subjects (n = 9). Circumferential strain (epsilon(cc)) was determined in 160 regions. From epsilon(cc) signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10-90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders (n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 +/- 6%, 21 +/- 16%, and 30 +/- 16%, respectively) significantly more (P < 0.05) than in nonresponders (1 +/- 6%, 3 +/- 4%, and 5 +/- 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 +/- 0.25 vs. 0.31 +/- 0.16; P < 0.05). In patients with ISF >0.4 (n = 10), LVESV decreased by 31 +/- 18% vs. 5 +/- 11% in patients with ISF <0.4 (P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.

Identification of ultrasound contrast agent dilution systems for ejection fraction measurements

Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.

Visual LV motion and invasive LVdP/dtmax for selection and optimisation of cardiac resynchronisation therapy

Echocardiography shows that multiphasic septal movement and a septal to lateral apical systolic left ventricular (LV) motion have a high predictive value for dyssynchrony and the response to cardiac resynchronisation therapy (CRT). Presence of dyssynchrony is also the major marker for CRT response in the presence of scar tissue, provided the interventricular (V-V) pacing interval is optimalised. For atrioventricular (AV) interval optimisation, the velocity-time integral of the transmitral flow has an excellent correlation with invasive LVdP/dtmax. In acute haemodynamic measurements, LVdP/dtmax shows strongly the effect of AV and V-V optimisation. It also illustrates that the haemodynamic effect of LV pacing when associated with intrinsic conduction over the right bundle is equal to or better than biventricular pacing. We found that once AV and V-V interval were optimised, QRS morphology could be used as a template for optimal therapy. Automated continuous optimisation of the pacing intervals will be the big challenge for the future. (Neth Heart J 2008;16(suppl 1):S32-S35).

Intra-thoracic blood volume assessment by dilution of ultrasound contrast agents

The blood volume assessment provides important information on the circulatory system condition. Especially the intra-thoracic blood volume (ITBV) is related to the symmetry of the cardiac efficiency. The ITBV measurement, nowadays, is made by use of trans-pulmonary indicator dilution techniques, such as thermo- and dye-dilution. Since catheterization is required, these techniques are very invasive. The tracer is injected into a central vein and detected in the aorta. The detected indicator concentration-versus-time curve is referred to as indicator dilution curve (IDC). The mean transit time (MTT) of the IDC multiplied by the cardiac output (CO) gives the blood volume between the injection site (central vein) and the aorta, i.e., the ITBV plus the average volume of all the cardiac chambers. This paper presents a new non-invasive technique for the measurement of blood volumes in the circulatory system. The tracer is an ultrasound contrast agent (UCA) detected by an ultrasound transducer. The acoustic or video intensity analysis of the B-mode output of ultrasound scanners allows the measurement of UCA IDCs. Several cardiac echo-views permit the measurement of different IDCs from different sites. The blood volume between two different sites is given by the product of the blood flow (CO) times the MTT that the contrast takes to go from the first to the second site. For the ITBV assessment, two IDCs can be measured simultaneously in the right and left side of the heart. The system is validated by in-vitro experimentation. A Sonos 5500 ultrasound scanner is used to detect SonoVue/spl reg/ contrast agent IDCs. The results show very accurate volume measurements with a standard deviation smaller than 4% of the volume for a wide range of flows. Initial in-vivo application of the system in humans shows promising results.

Assessment of ventricular mechanical dyssynchrony by short-axis MRI

Nowadays, patients with symptomatic heart failure and intraventricular conduction delay can be treated with a cardiac resynchronization therapy. Electrical dyssynchrony is typically adopted to represent myocardial dyssynchrony, to be compensated by cardiac resynchronization therapy. One third of the patients, however, does not respond to the therapy. Therefore, imaging modalities aimed at the mechanical dyssynchrony estimation have been recently proposed to improve patient selection criteria. This paper presents a novel fully-automated method for regional mechanical left-ventricular dyssynchrony quantification in short-axis magnetic resonance imaging. The endocardial movement is described by time-displacement curves with respect to an automatically-determined reference point. These curves are analyzed for the estimation of the regional contraction timings. Four methods are proposed and tested for the contraction timing estimation. They were evaluated in two groups of subjects with and without left bundle branch block. The standard deviation of the contraction timings showed a significant increase for left bundle branch block patients with all the methods. However, a novel method based on phase spectrum analysis shows a better specificity and sensitivity. This method may therefore provide a valuable prognostic indicator for heart failure patients with dyssynchronous ventricular contraction, adding new possibilities for regional timing analysis.

Contrast Ultrasound Methods for Left-Ventricle Ejection Fraction Measurements

The left-ventricle ejection fraction is an important cardiac-efficiency measure that is regularly used in cardiology. Standard estimations are based on time-consuming geometrical analysis and modelling, which requires experienced cardiologists. Alternative methods are very invasive due to the need for cardiac catheterization. In this paper we present and study a minimally-invasive indicator dilution technique for ejection fraction quantification that has recently been developed. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left-atrium and left-ventricle acoustic intensities are recorded versus time by transthoracic echocardiography during contrast bolus passage. The measured curves are corrected for attenuation distortion, filtered to suppress the measurement noise, and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left-ventricle impulse response. The estimated impulse response is interpolated by a mono-compartment exponential model for the ejection fraction assessment. An adaptive search of the interval for the model fitting is also included. The feasibility of the method is tested on 52 measurements in patients with left-ventricle ejection fractions between 10% and 80%. The results are promising and show a 0.83 correlation coefficient with echographic bi-plane ejection fraction measurements