Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Abstract

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment.

Figure 1

Paradigms in cardiac resynchronization therapy. Schematic representation of two paradigms of mechanical dyssynchrony in cardiac resynchronization therapy. The left panel shows a "binary approach", according to which mechanical dyssynchrony above a certain cut-off is associated with a benefit from CRT (open circles), whereas dyssynchrony below that cut-off is associated with no benefit (solid circle). The right panel depicts the "lower/upper cut-off approach", according to which patients within a finite range of mechanical dyssynchrony benefit from CRT (open circles), whereas patients with too much dyssynchrony (above the upper cut-off) or too little dyssynchrony (below the lower cut-off) do not benefit (closed circles). It is hypothesized that, outside the critical range, alternative pacing modes (endocardial pacing, LV pacing with multiple leads) may be more effective than conventional CRT. Reproduced with permission from Auricchio and Leyva [128].

Figure 2

Wall motion analysis using SSFP sequences. Wall motion analysis using SSFP sequences involves division of the left ventricular myocardium into slices and segments (a). The latter extend clockwise from the junction between the interventricular septum and the right ventricular free wall (beginning of segment 1 and end of segment 6) (b). As shown in (c), the concordance of radial wall motion observed in healthy control subjects is highly disrupted in patients with heart failure and a left bundle branch block (LBBB).

Figure 3

Echocardiographic and CMR measures of dyssynchrony in heart failure. Distribution of dyssynchrony measures obtained from echocardiography and CMR. The standard deviation of the time to peak myocardial sustained systolic velocity (Ts-SD) of 12 left ventricular segments (a) and the CMR-tissue synchronization index CMR-TSI) (b) in controls and in patients with heart failure (HF), stratified according to QRS duration. Note the considerable overlap between healthy controls and patients with heart failure. Adapted with permission from a) Yu C-M et al [30] and (b) Foley et al. [38]

Figure 4

CMR-TSI and outcome of CRT. Kaplan-Meier estimates of the time to the composite endpoint of death from any cause or hospitalization for a major cardiovascular event (MCE) after CRT.. Patients were stratified according to a pre-implant CMR-TSI < 110 ms or CMR-TSI ≥ 110 ms. Results of univariate Cox proportional hazards analyses are expressed in terms of the hazard ratio (HR) and 95% confidence limits. Reproduced with permission from Chalil S, et al. [34]

Figure 5

Derivation of the internal flow fraction. (a) For the calculation of internal flow fraction, the three-dimensional LV volume is superimposed on the four-chamber long-axis and short axis SSFP images and the left ventricle is divided into 16 wedge-shaped regional volumes. (b) the Internal Flow Fraction discriminates between patients and healthy controls with 95% accuracy. Reproduced with permission from Fornwalt BK, et al. [46]

Figure 6

Relationship between strain and tag frequency for harmonic phase-based strain measurements. A)Contraction of a tagged fibre in the middle increases the tagging frequency (density of tag lines), as shown for the top fibre. Stretching causes a reduction in local frequency. (B) Two-dimensional segmentation of the heart and mesh generation (top panel) and regional strain versus time plots over the cardiac cycle; (C) complete regional strain versus time plots over the cardiac cycle for all segments. ECC = circumferential strain. Reproduced with permission from Lardo et al. [129]

Figure 7

Dyssynchrony indexes and regional distribution of wall motion. Schematic representation of net dyssynchrony based on spatial distribution of delayed activation. When regions of delayed activation are clustered, the net impact on dysfunction is greater than when they are dispersed. Both situations are associated with similar overall numbers of delayed segments overall, as well as similar variance and dyssynchrony indexes. In contrast, a vector index would be zero for dispersed dyscoordinate shortening but non-zero when dyscoordinate motion is spatially clustered. Reproduced from Helm RH, et al. [52]

Figure 8

Concordance between the CURE index and mechanical resynchronization. A) Three-dimensional plot of relative mechanical activation time (time from QRS to peak circumferential strain) in a dog model of a dyssynchronous failing heart (with left bundle-branch block) and during CRT (biventricular pacing). The green dot shows the LV stimulation site. B) Synchrony indexed by CURE was calculated as a function of varying LV pacing site and plotted on three-dimensional maps, in which the colour red denotes optimal mechanical resynchronization. C) Combined maps derived for ventricular stroke work and synchrony (CURE) were determined in four failing hearts, and the territories producing optimal responses (70% maximal) for both were calculated and are displayed in green (far right). Adapted from Helm RH, et al. [54]

Figure 9

Twist mechanics of the left ventricle. Following electrical and mechanical activation in the apical subendocardial region, there follows a period of left ventricular isovolumic contraction (IVC), during which (A), the subendocardial myofibers (right-handed helix) shorten with stretching of the subepicardial myofibres (left-handed helix) to effect clockwise rotation of the apex and counterclockwise rotation of the base. During ejection (B), there is simultaneous shortening of the subendocardial and subepicardial layers. The larger arm of moment of the subepicardial fibers dominates the direction of twist, causing counterclockwise and clockwise rotation of the apex and base, respectively. During isovolumic relaxation (IVR) (C), subepicardial fibres lengthen from base to apex and subendocardial fibres lengthen from apex to base. In diastole, there is relaxation in both layers, with minimum untwisting (D). Reproduced with permission from Sengupta PP, et al. [56]

Figure 10

Three-dimensional tagging and optical flow methodology. Images from a technique involving a three-dimensional CMR tagging sequence and an optical flow method to measure three-dimensional LV wall deformation in a single cine acquisition. Panels A to C illustrate the maximum principal strain (ε₁) on three representative short axis slices. The colour of the plot and the length of the overlaid line segments correspond to the magnitude of the strain while the direction is indicated by the vector. The images show the minimum ε₁ in the septum and the maximum ε₁ in the lateral wall. Panel D shows a mid-wall surface colour-coded by with ε₁, with superimposed eigenvector direction at four longitudinal levels. Note that ε₁ is directed towards the centre of the LV, indicating in-plane radial thickening.

Figure 11

Radial wall motion mapping with CMR. The phase of inward radial wall motion is represented by colours ranging from blue (zero phase shift: inward motion during global systole), to green (90° phase shift: inward motion at the end of global systole) and to red (180° phase shift: inward motion during global diastole). Accordingly, the bull's eye with a homogenous blue colour throughout denotes complete synchrony, whereas a bull's eye with a homogenous red colour throughout denotes complete synchrony. Heterogenouss colour coding denotes dyssynchrony of radial motion, with blue representing early (global systolic phase) activation and red representing late (global diastolic phase) inward radial wall motion. Note the patchy distribution of wall motion throughout the LV. Reproduced with permission from Foley P, et al. [38]

Figure 12

Effect of scar transmurality on outcome after CRT. Kaplan-Meier estimates of the time to clinical endpoints in patients with non-LV free wall scars, transmural LV free wall scars and non-transmural LV free wall scars. Adapted from Chalil S, et al. [89]

Figure 13

Effect of LV pacing site scar on the clinical response to CRT. Box and whisker plots of changes in 6-min walking distance and quality of life (QoL) in patients with LV free wall scars, grouped according to relationship of LV pacing lead tip to scar or non-scar. The five horizontal lines represent the 10^th, 25^th, 50^th, 75^th and 90^th percentiles of each variable, from bottom to top. Reproduced from Chalil S, et al.[89]

Figure 14

Effect on clinical outcome of pacing LV free wall scar in CRT. Kaplan-Meier estimates of the time to cardiovascular death or hospitalization for heart failure in patients with a LV free wall scar, grouped according to whether the LV lead was deployed over the scar or outside the scar. Hazard ratios and 95% confidence intervals derived from univariate Cox proportional hazards analyses are shown in parentheses. The right sided panels show representative short axis LGE-CMR slices of lead deployments on the scar and outside the scar. Adapted from Chalil S, et al. [95]

Figure 15

Combined dyssynchrony and scar maps. Endocardial wall motion and scar were quantified using SSFP and LGE-CMR, respectively. The color-encoded regional delay of radial inward motion is mapped onto a bull's eye map and LV model, pictured from above (middle figure) and below (bottom figure). Timing of radial inward motion is expressed as a phase delay ranging from zero to 180°. A phase delay of zero represents early ventricular motion concordant with initial electrical activation and is colour coded blue, while a phase delay of 180° denotes diastolic inward motion and is colour coded red. The LV free wall scar (grey-black) is superimposed on the endocardial wall motion map. In the figure, the LV septum is contracts early in systole and the inferior wall close to the LV free wall scar shows abnormal diastolic radial inward motion. Note the patchy distribution of wall motion throughout the left ventricle. Reproduced with permission from Foley P, et al. [38]

Figure 16

The DSC index as a composite predictor of outcome after CRT. Graph shows Kaplan-Meier estimates of the time to cardiovascular death. Patients were stratified according to pre-implant Dyssynchrony, left ventricular free wall Scar and Creatinine (DSC) index. The event rate, number of patients in the DSC risk stratum and the% event rate are shown in parentheses. The hazard ratio (HR) and 95% confidence intervals are also shown. Reproduced with permission from Leyva F, et al. [130]

Figure 17

Assessment of heart failure etiology with CMR. A) LGE-CMR short axis slice showing a subendocardial myocardial infarction in the territory of the left anterior descending artery; B) LGE-CMR short axis slice showing a transmural myocardial infarction the territory of the circumflex artery; C) LGE-CMR showing a transmural myocardial infarction in the territory of the right coronary artery, which is associated with marked myocardial thinning.; D) Patchy LGE characteristic of myocarditis.; F) Mixed cardiomyopathy: left ventricular non-compaction cardiomyopathy and ischemic cardiomyopathy. Note the transmural inferior myocardial infarction (see insert for LGE-CMR) which has led to myocardial thinning.; G) Four-chamber and short-axis LGE-CMR images showing mid-wall LGE, denoting fibrosis, in idiopathic dilated cardiomyopathy.