MRI methods for predicting response to cardiac resynchronization therapy

Cardiac Resynchronization Therapy (CRT) is a treatment option for heart failure patients with ventricular dyssynchrony. CRT corrects for dyssynchrony by electrically stimulating the septal and lateral walls of the left ventricle (LV), forcing synchronous con- traction and improving cardiac output. Current selection criteria for CRT rely upon the QRS duration, measured from a surface electrocardiogram, as a marker of electrical dyssynchrony. Unfortunately, 30-40% of patients undergoing CRT fail to benefit from the treatment. A multitude of studies have shown that presence of mechanical dyssynchrony in the LV is an important factor in determining if a patient will benefit from CRT. Furthermore, recent evidence suggests that patient response can be improved by placing the LV pacing lead in the most dyssynchronous or latest contracting segment. The overall goal of this project was to develop methods that allow for accurate assessment and display of regional mechanical dyssynchrony throughout the LV and at the site of the LV pacing lead. To accomplish this goal, we developed a method for quantifying regional dyssynchrony from standard short-axis cine magnetic resonance (MR) images. To assess the effects of LV lead placement, we developed a registration method that allows us to project the LV lead location from dual-plane fluoroscopy onto MR measurements of cardiac function. By applying these techniques in patients undergoing CRT, we were able to investigate the relationship between regional dyssynchrony, LV pacing lead location, and CRT response.Ph.D

A method to determine regional mechanical left ventricular dyssynchrony based on high temporal resolution short axis SSFP cine images

Left ventricular (LV) mechanical dyssynchrony has been proposed as a parameter to select patients for cardiac resynchronization therapy (CRT) [Bax et al JACC 2005].Several recent studies have shown that placing the LV pacing lead in the most delayed regions yields a better response to CRT [Ansalone et al JACC 2002]. However, most imaging-based methods assess global LV dyssynchrony providing a single value for the entire LV. Regional maps of LV dyssynchrony are required for planning LV lead placement. The objective of this study was to develop a method to create a map of regional left ventricular mechanical dyssynchrony based on short-axis SSFP cine images

Characterization of the size and location of dyssynchronous regions in patients undergoing CRT

The amount and location of left ventricular (LV) mechanical dyssynchrony affects an individual’s ability to respond positively to cardiac resynchronization therapy (CRT) [Bax et al JACC 2005]. By using high temporal resolution short-axis cines, it is possible to derive radial motion curves throughout the LV. These radial motion curves can be used to create maps showing dyssynchronous regions in patients enrolled for CRT. The objective of this study was to characterize the size and location of areas of mechanical dyssynchrony in patients scheduled for CRT by comparing their radial wall motion curves to radial motion curves from normal subjects

Two-Dimensional Estimates of Left Ventricular Strains are Significantly Affected by Through-Plane Motion

Background Advanced measures of cardiac mechanics such as left ventricular (LV) strains can be used in conjunction with classical biomarkers to gauge cardiovascular health and improve prediction of patient outcomes. Several imaging techniques, including displacement-encoded magnetic resonance imaging (DENSE), are used to non-invasively assess cardiac mechanics. These data are predominantly acquired in two dimensions (2D) due to simplified post-processing and shorter acquisition times; however, this type of acquisition and subsequent analysis cannot account for through-plane motion caused by longitudinal contraction of the left ventricle. We hypothesized that through-plane motion has a significant effect on 2D strain estimates. Methods Cine DENSE data were acquired in eight healthy volunteers (Age: 27 ± 3 years) with a 3T Siemens Tim Trio scanner. Short-axis slices with 2.8 mm in-plane resolution and an 8 mm slice thickness were acquired to span the entire LV. Displacements were encoded in both through-plane and in-plane directions with an effective temporal resolution of 34 ms. Endocardial and epicardial boundaries were delineated on the magnitude image of all short axis DENSE images. Radial and circumferential strains were computed based upon the deformation of the myocardium relative to the end-diastolic frame. Through-plane displacements were ignored for 2D analysis. For three-dimensional (3D) analysis, a 3D representation of the myocardium derived from the same endocardial and epicardial boundaries was deformed using the measured displacement field. The resulting radial and circumferential strain values were compared directly between the 2D and 3D analyses using a two-tailed paired t-test. Results Two dimensional processing consistently overestimated radial strain and underestimated circumferential strain. Peak circumferential strain was significantly different at the basal and mid-ventricular segments (p = 0.001 and 0.009, respectively). Peak radial strain decreased from the base to the apex in both 2D and 3D analyses; however, 2D significantly overestimated radial strain at the mid-ventricular and apical slices compared to 3D (p = 0.002). Global peak radial and circumferential strains from 3D were 30 ± 5% and -20 ± 2%, respectively, compared to 36 ± 5% and -18 ± 2% for 2D (both p \u3c 0.001). Conclusions Two-dimensional imaging methods for assessing left ventricular mechanics consistently overestimate radial strain and underestimate circumferential strain when compared to three-dimensional imaging. This limitation of two-dimensional imaging is likely due to the through-plane motion of the heart, which is ignored in two-dimensional techniques but easily accounted for when using three-dimensional techniques. Future research needs to determine the clinical and prognostic significance of this difference. Funding This research was funded in part by an NIH Early Independence Award to BKF (DP5 OD012132); contributions made by local businesses and individuals through a partnership between Kentucky Children\u27s Hospital and Children\u27s Miracle network; and the University of Kentucky Cardiovascular Research Center, grant UL1RR033173 from the National Center for Research Resources (NCRR), funded by the Office of the Director, National Institutes of Health (NIH) and supported by the NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources

Assessment of intra- and inter-ventricular cardiac dyssynchrony in patients with repaired Tetralogy of Fallot: a cardiac magnetic resonance study

Background Patients with repaired tetralogy of Fallot (TOF) frequently have right bundle branch block. However, the contribution of cardiac dyssynchrony to dysfunction remains controversial. To better understand this phenomenon and ultimately study therapies, we developed a method to quantify left (LV), right (RV) and inter-ventricular cardiac dyssynchrony using standard cine CMR. Methods 30 patients with repaired TOF (age 28 ± 16, 46% female) and 17 healthy controls (age 29 ± 7, 12% female) underwent cine CMR. Patients were imaged twice to assess inter-test reproducibility. Circumferential strain vs time curves were generated with a custom feature tracking algorithm for 12 LV and 12 RV segments in 4-7 slices encompassing the ventricles. For each segment, the temporal offset (TO) of the strain curve relative to a global reference curve derived from the controls was calculated and expressed as a percent of the cardiac cycle. The intra-ventricular dyssynchrony index (DI) for each ventricle was computed as the standard deviation (SD) of the TOs (more dyssynchrony increases the SD). The inter-ventricular DI was calculated as the difference in median RV and median LV TOs. Regional dyssynchrony was quantified in 3 LV (septum, infero-lateral and antero-lateral wall) and 3 RV (septum, sinus, outflow tract) regions using median TOs. Results Compared to controls, patients with repaired TOF had a greater LV, RV and inter-ventricular DI. The greater inter-ventricular delay in the patients was primarily due to a global delay in RV contraction with the RV contracting 4.9 ± 3.5% later than the LV in patients vs 1.4 ± 3.2% earlier in controls. Median TOs were similar in the three LV regions between patients and controls, but all three RV regions were significantly delayed in patients compared to the controls. Contraction patterns in the RV were also distinct: in controls, the earliest contraction was seen in the outflow tract; in patients, contraction occurred first in the septum and last in the outflow tract. Inter-test reproducibility for the three DIs was good with all coefficients of variation Conclusions Patients with repaired TOF suffer from left, right and inter-ventricular cardiac dyssynchrony which can all be quantified from standard cine CMR with good inter-test reproducibility. Future studies need to determine whether these patients may benefit from resynchronization therapy