The Year in Imaging Related to Electrophysiology
Laurens F. Tops, MD,
Jeroen J. Bax, MD, PhD*
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Key Words: echocardiography • computed tomography • cardiac magnetic resonance • atrial fibrillation • ventricular tachycardia • cardiac resynchronization therapy
Imaging is crucial in performing electrophysiological procedures, such as catheter ablation procedures and pacemaker implantations. Various imaging modalities are available to assist in the pre-procedural selection of patients, to depict the anatomic substrate of the arrhythmia during the procedure, or to assess the effects of the electrophysiological procedure. In the past year, important clinical and pre-clinical studies have been published that have expanded the role of various imaging modalities in electrophysiological procedures. This article reviews the most important studies related to imaging and the invasive treatment of atrial fibrillation (AF) and ventricular tachycardia (VT), and to cardiac resynchronization therapy (CRT).
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AF
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At present, catheter ablation for AF is considered a reasonable option when antiarrhythmic drugs have failed. The cornerstone for most AF ablation procedures is the electrical isolation of the pulmonary veins. The role of imaging in catheter ablation for AF is mainly related to the intraprocedural visualization of the pulmonary veins, guidance of the ablation catheter, and follow-up of patients after catheter ablation.
Imaging During Catheter Ablation.
A large number of imaging modalities are available for visualization of the left atrium (LA) and pulmonary veins during catheter ablation. Recently, new technologies and image integration strategies have been introduced. These techniques are reviewed in the following paragraphs.
Robotic navigation
A prospective multicenter study was conducted to evaluate the safety and efficacy of a new robotic navigation system (SenseiRobotic Catheter System, Hansen Medical, Mountain View, California) (1). This system consists of a physician workstation and a remote catheter manipulator that directly controls a robotic catheter. This hollow catheter consists of a guide sheath system and contains the mapping/ablation catheter. In this study, a 3.5-mm Thermocool catheter (Navistar, Biosense Webster, Diamond Bar, California) was used to perform ablation along the pulmonary vein antrum and superior vena cava. A total of 40 patients from 3 different centers in Europe were studied. In all patients, the pulmonary veins and the superior vena cava were successfully isolated. Complications included pericardial tamponade requiring pericardiocentesis in 2 patients (1 related to a nonrobotic transseptal procedure, 1 caused by ablation using the robotic system). After 12 months of follow-up, 34 of the 40 patients (85%) were free from atrial arrhythmias without any antiarrhythmic drug. This first multicenter study shows that robotic navigation is a promising technique for AF ablation. Potential advantages of this system include easier navigation, more precise and stable catheter positioning, and a reduction in radiation exposure to the physician. However, more studies are needed to investigate whether this new technology results in an improved outcome of the ablation procedure.
Image integration: fluoroscopy and multislice computed tomography (MSCT)
Real-time integration of 64-slice MSCT and biplane fluoroscopy was used in 60 patients referred for AF ablation (2). Image integration was performed with custom made software, using the 3-dimensional (3D) MSCT surface model and the angiographic reconstruction of the LA and pulmonary veins on fluoroscopy. Two integration strategies (visual matching of the 2 structures and landmark-based registration) were tested (Fig. 1). With the use of 11 ± 2 landmark pairs, landmark registration yielded the best integration accuracy: the mean alignment error was 2.0 mm on the right anterior oblique view (range 0.5 to 5.0 mm) and 2.0 mm on the left anterior oblique view (range 0 to 4.0 mm). Clinically relevant changes in alignment error were not observed for various MSCT scanning protocols (with vs. without electrocardiographic gating, inspiratory vs. expiratory breath hold). The integration of MSCT and biplane fluoroscopy has great potential because it enables real-time visualization of the ablation catheter in relation to pulmonary vein anatomy derived from high-resolution images.
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Figure 1 Image Integration: Fluoroscopy and MSCT
Different registration approaches are used for three-dimensional (3D)-augmented fluoroscopy. The upper panel is an illustration of the visual matching registration approach. After calibration of the fluoroscopic images by marking 7 electrodes on the coronary sinus catheter, a rigid registration is performed by manually translating and rotating the integrated 3D model with a 3D spacemouse to align it with the angiographic reference image. The lower panel is an illustration of the landmark-based registration approach. A number of correspondences are marked at clearly identifiable landmarks on the angiographic image (left) and on the 3D model (right) shown from a corresponding view angle. A 3D–2-dimensional registration function is then automatically computed to register the 3D model with the angiographic reference image. The accuracy of the integration process is represented by the alignment error that was defined as the distance between the pulmonary vein ostium on the angiographic image and its position on the 3D multislice computed tomography (MSCT) surface model. Reprinted with permission from Ector et al. (2).
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Image integration: mapping and MSCT
A new image integration system that allows the integration of MSCT and nonfluoroscopic electroanatomic mapping (NavX Fusion, St. Jude Medical, St. Paul, Minnesota) has recently been introduced (3). Brooks et al. (3) used this novel technology in 55 patients referred for AF ablation. After field scaling of the reconstructed geometry, landmark pairs were used to fuse the MSCT image and the reconstructed map. Secondary markers were used to mold the reconstructed map into the MSCT image. After the complete registration process, the mean distance between the MSCT and the reconstructed geometry was 1.9 ± 0.4 mm. Although this study shows the feasibility of this new image integration system, the time interval between MSCT scanning and the actual ablation procedure, resulting in differences in LA geometry caused by changes in heart rhythm, fluid status, and respiration, remains a limitation.
Image integration: mapping and intracardiac echocardiography (ICE)
The feasibility of the integration of real-time ICE and electroanatomic mapping was recently shown (4,5). The new CartoSound system (Biosense Webster) contains an ICE catheter (Soundstar, Biosense Webster) that is equipped with an electroanatomic location sensor. By tracing endocardial surface contours on the imported ultrasound images, 3D reconstructions of the LA and pulmonary veins can be created (Fig. 2). To test the feasibility and accuracy of this new technique, Okumura et al. (4) implanted marker clips percutaneously on distinct anatomical locations, such as the pulmonary vein orifice and LA appendage in 12 mongrel dogs. Subsequently, the 3D ultrasound geometry of the LA and pulmonary veins was created with the use of 22 ± 5 contours. Mean registration error between this ultrasound reconstruction and the imported MSCT surface image was 1.7 ± 0.4 mm. Finally, ablation lesions were targeted at the implanted clips, guided by the 3D ultrasound geometry. At autopsy, the mean distance between the radiofrequency lesions and the target clips was 1.1 ± 1.1 mm (range 0 to 4.3 mm).
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Figure 2 Image Integration: Mapping and ICE
The new CartoSound system (Biosense Webster) enables the reconstruction of the LA and pulmonary veins from real-time ICE images. In the top panel, the map viewer (top left) and the ultrasound viewer (top right) are shown. Endocardial contours of the LA border and the pulmonary veins (white arrows) are drawn. With the use of multiple contours (bottom left panel), a 3D map is created. The completed electroanatomic map is subsequently merged with a 3D MSCT image (bottom right panel). ICE = intracardiac echocardiography; LA = left atrial; other abbreviations as in Figure 1.
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den Uijl et al. (5) used the same technology in 17 patients undergoing catheter ablation. A mean of 31 ± 9 ICE contours (range 18 to 43) were used to reconstruct the LA and pulmonary veins. Mean distance between the reconstructed ICE image and the MSCT was 2.2 ± 0.3 mm (range 1.7 to 2.8 mm). The ability to integrate electroanatomic data with ultrasound images is a promising concept. Creating a 3D reconstruction of the LA and pulmonary veins using ICE without entering the LA may reduce procedure time and enhance the safety of catheter ablation procedures. More studies in larger populations are needed to confirm the results of these first feasibility studies.
Impact of image integration on ablation outcome
Although the use of image integration greatly facilitates the intraprocedural visualization of the LA and pulmonary veins, the exact effects of image integration on the procedure/fluoroscopy time and the outcome of the ablation procedure remain controversial. Unfortunately, there is a clear lack of prospective, randomized studies that address this issue. A recent study showed that the integration of MSCT and electroanatomic mapping using CartoMerge may improve the outcome of the ablation procedure. In a series of 100 patients, the overall success after 6 months of follow-up was significantly improved in the image integration group, as compared with the group in which conventional electroanatomic mapping was used (85.1% vs. 67.9%, p = 0.018) (6). In addition, it has been suggested that the integration of MSCT and fluoroscopy is associated with a reduced fluoroscopy and procedure time (2). However, more prospective, randomized studies are warranted to further confirm these findings.
Rotational angiography
This new C-arm flat-panel fluoroscopy system may overcome the need for image integration because real-time 3D images can be obtained during the ablation procedure. The first clinical experience with this technique has been reported in 42 patients undergoing AF ablation (7). Rotational angiography was performed in the electrophysiology laboratory using an X-ray FD10 flat-detector system (Allura XPer, Philips Medical Systems Inc., Best, the Netherlands). The volume-rendered reconstruction of the LA and pulmonary veins was compared with pre-procedural acquired MSCT and cardiac magnetic resonance (CMR) images. The investigators classified 12 of the 42 images (29%) as nondiagnostic, whereas 23 (55%) were useful and 7 (17%) were optimal. Quantitative analyses showed a mean difference in pulmonary vein diameter of 0.2 ± 3.3 mm between rotational angiography and MSCT and 0.2 ± 3.1 mm between rotational angiography and CMR. Refinement of the imaging protocol and technical adjustments may further enhance the image quality and usefulness of this novel technique.
Imaging After Catheter Ablation.
Catheter ablation procedures offer a good therapeutic option in patients with drug-refractory, symptomatic AF. However, the exact effect of catheter ablation on LA function is not yet fully understood. In the past year, a number of studies have used new techniques that may provide more insight into the effects of catheter ablation procedures, by more accurately assessing LA volumes, LA deformation properties, and the extent of LA scar.
Left atrial volumes and function
Although LA volumes and function are typically assessed with conventional 2-dimensional echocardiography, this technique is limited by the significant geometric assumptions and relatively low reproducibility for LA volume assessment. New real-time 3D echocardiography offers more accurate and reproducible quantification of LA volumes and function. In 57 patients undergoing catheter ablation for AF, real-time 3D echocardiography was used to assess LA volumes and function at baseline and after 3 months of follow-up (8). Left atrial active contraction and LA reservoir function were derived from the maximum and minimum LA volumes and the LA volume just before the P-wave. In patients who maintained sinus rhythm during follow-up (n = 38, 67%), a significant decrease in LA volumes was noted, whereas in patients who had recurrence of AF (n = 19, 33%), a trend toward an increase in LA volumes was noted. In addition, LA active contraction and LA reservoir function significantly improved in patients who maintained sinus rhythm, as compared with patients who had a recurrence of AF (LA active 33 ± 9% vs. 15 ± 9%, p < 0.001; LA reservoir 152 ± 54% vs. 78 ± 35%, p < 0.001). The investigators suggested that because no changes in left ventricular (LV) systolic and diastolic function were observed, these changes in LA active and reservoir function are probably related to the favorable effect of long-term maintenance of sinus rhythm after catheter ablation (8).
Schneider et al. (9) used tissue Doppler imaging to assess LA function after catheter ablation in 118 AF patients. This technique enables quantification of intrinsic LA function by evaluation of myocardial deformation properties. In various LA segments, strain and strain rate values were acquired to assess LA reservoir function (at midsystole) and LA active contraction (at end-diastole). After 3 months of follow-up, patients who maintained sinus rhythm showed significant higher peak systolic atrial strain and end-diastolic atrial strain rate values as compared with patients who had recurrence of AF. Interestingly, atrial septal systolic strain (reflecting LA reservoir function) best predicted maintenance of sinus rhythm during follow-up (cutoff value 20.5%; sensitivity 99%, specificity 78%; area under the receiver-operator characteristic curve 0.998). These studies suggest that successful catheter ablation improves both LA reservoir function and LA active contraction. More studies are needed to fully understand the exact mechanism of this LA reverse remodeling and functional improvement after catheter ablation.
Detection of LA scar
The relationship between electrical isolation of the pulmonary veins and anatomical findings, such as scar formation, remains uncertain. In addition, it would be of interest to correlate the extent of scarring with the clinical outcome of the procedure. For in vivo imaging of LV scar, delayed-enhancement CMR is considered the gold standard. Peters et al. (10) used high-resolution 3D navigator-gated contrast-enhanced CMR to detect LA scar, both before and after catheter ablation. After ablation, all patients showed delayed enhancement (i.e., scarring) at the ostia of the pulmonary veins. Semiquantitative analysis of obliquely reformatted images of the left inferior pulmonary veins showed an average circumferential extent of delayed enhancement of 88 ± 11%.
Similarly, McGann et al. (11) studied 53 patients at baseline and 3 months after ablation with contrast-enhanced CMR (3D inversion respiration-navigated gradient echo pulse sequence). Using a threshold-based lesion detection algorithm, the extent of LA scar relative to the total LA area was assessed. Contrast enhancement was present on the post-ablation images in all patients, and was mainly located on the LA posterior wall, around the pulmonary vein ostia and on the interatrial septum (Fig. 3). Interestingly, in patients with recurrence of AF at 3-month follow-up, a smaller scar area was noted as compared with patients who maintained sinus rhythm (12.4 ± 5.7% vs. 19.3 ± 6.7%, p = 0.004). Large scar areas (>13% of total LA area) were highly predictive for maintenance of sinus rhythm at follow-up (odds ratio: 18.5; 95% confidence interval: 1.27 to 268, p = 0.032). These studies show that contrast-enhanced CMR may provide more insight in the extent of (transmural) scarring of the LA wall after catheter ablation. Thereby, it may help in optimizing ablation strategies and the approach to patients who have recurrence of AF after ablation.
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Figure 3 LA Injury Before and After Catheter Ablation for AF
This figure shows 3D DE-CMR images of the LA before PVAI and 3 months after PVAI. Left panels show LA wall slices at baseline (A) and 3 months after PVAI (B) on 3D navigated DE-CMR in 4 different patients. Right panels show 3D rendering of LA in patient #1 before and after PVAI in multiple views (posterior, right, left, and superior) reconstructed from CMR slice data. Post-PVAI hyperenhancement of the LA wall is clearly seen (yellow arrows) in regions subjected to radiofrequency ablation and suggests scarring. Reprinted with permission from McGann et al. (11). CMR = cardiac magnetic resonance; DE = delayed-enhancement; PVAI = pulmonary vein antrum isolation; other abbreviations as in Figures 1 and 2.
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VT
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In the past year, a number of interesting studies have been published that have expanded the role of various imaging modalities in the diagnosis and treatment of VT. In particular, imaging may play an important role in the prediction of the occurrence/inducibility of VT and the invasive treatment with catheter ablation.
Occurrence and Inducibility of VT.
In 3 studies, different imaging techniques were used to correlate anatomical findings with the occurrence and inducibility of VT to better identify patients who are at risk for VT. The interface between myocardial scar tissue and normal myocardium may play an important role in the pathogenesis of re-entrant VT. Fernandes et al. (12) used contrast-enhanced and tagged CMR to study the possible correlation between the inducibility of VT and: 1) the extent of scar; and 2) the mechanical properties of myocardial regions at various distance from the infarcted tissue. These regions were defined as infarct, border zone, adjacent, or remote, based on the amount of scar tissue assessed with contrast-enhanced CMR. The mechanical properties of the different regions were assessed with the use of circumferential strain and time-to-peak circumferential strain. Forty-six patients, referred for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden cardiac death after myocardial infarction, were studied. In 19 patients, a monomorphic VT was inducible during programmed ventricular stimulation. In the inducible patients, a greater percentage of infarcted and border zone segments were present, as compared with noninducible patients (infarcted 47.0% vs. 38.2%, p < 0.001; border zone 23.1% vs. 21.5%, p < 0.001). Interestingly, the border zone segments showed significant higher strain values in the inducible patients compared with the noninducible patients (–11.42 ± 0.46 vs. –10.18 ± 0.38, p < 0.05). In addition, time-to-peak strain was significantly shorter in the infarcted and border zone regions of inducible patients, as compared with noninducible patients. The investigators concluded that an enhanced border zone function (represented by a greater myocardial shortening and a shorter time-to-peak strain) is associated with inducibility of VT in ischemic cardiomyopathy. Although the exact mechanism needs to be elucidated, this study may add to a better understanding of the underlying pathophysiology of re-entrant VT and may strengthen the role of noninvasive imaging in the identification of patients who are at risk for VT.
In another study, the relationship between changes in cardiac sympathetic innervation/denervation and the inducibility of VT was explored in 50 patients referred for electrophysiological study, with a history of myocardial infarction and LV ejection fraction <40% (13). Because viable but denervated myocardium is very sensitive to sympathetic stimulation, it may play a role in the arrhythmogenesis in patients with ischemic cardiomyopathy. In this prospective multicenter trial, early and late planar and single-photon emission computed tomography (SPECT) 123I-mIBG scintigraphy and SPECT imaging with 99mTc-tetrofosmin was performed to assess the sympathetic innervation/denervation and infarct size. In 30 patients (60%), a sustained VT was induced. Standard 123I-mIBG measures, such as the early and late heart/mediastinum ratio, and 123I-mIBG-perfusion mismatch were not significantly different between the inducible and noninducible patients. However, the late SPECT 123I-mIBG summed score or defect size, representing global denervation, was significantly higher in the inducible patients as compared with the noninducible patients (42.7 ± 8.8 vs. 34.9 ± 9.8, p < 0.01). At multivariable analysis, this parameter was the only predictor for the inducibility of VT. Although the results are promising, more studies are needed to confirm the possible association between the extent of denervation on 123I-mIBG SPECT and VT inducibility.
Finally, in a cohort of 177 patients with hypertrophic cardiomyopathy, contrast-enhanced CMR was used to study the correlation between the extent of LV scar and the occurrence of VT (14). The large majority of patients (95%) was asymptomatic; mean LV wall thickness was 21 ± 5 mm (range 10 to 36 mm). In 72 patients (41%), scar tissue on CMR was present, occupying 9 ± 8% (range 0.6% to 37.6%) of the LV myocardium. Premature ventricular contractions, couplets, and nonsustained VT were more common in patients with versus without scar on CMR. Interestingly, scar tissue on CMR was an independent predictor of nonsustained VT (relative risk: 7.3, 95% confidence interval: 2.6 to 20.4, p < 0.001). The investigators concluded that contrast-enhanced CMR may help in the identification of hypertrophic cardiomyopathy patients who are at risk for VT (14).
Mapping and Ablation of VT.
In the past year, the SMASH-VT (Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia) study showed that prophylactic substrate-based catheter ablation may significantly reduce the incidence of VT in patients with ischemic cardiomyopathy and an ICD for secondary prevention (15) (Fig. 4). This study further expands the role of substrate-based VT ablation in patients with ischemic cardiomyopathy. For catheter ablation of ischemic VT, delineation of the anatomical substrate of the VT is of critical importance. Typically, voltage mapping with the use of an electroanatomic mapping system is performed to locate areas of scar tissue. In the past year, a number of studies have been published that use an integrated imaging approach for the depiction of the anatomical substrate, or use novel imaging techniques to guide VT ablation.
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Figure 4 Kaplan-Meier Estimate of the Primary End Point of Survival Free From ICD Therapy in the SMASH-VT Study
Twenty-one patients assigned to defibrillator implantation alone (33%) and 8 patients assigned to defibrillator implantation plus ablation (12%) received appropriate implantable cardioverter defibrillator (ICD) therapy (antitachycardia pacing or shocks) (hazard ratio in the ablation group: 0.35; 95% confidence interval: 0.15 to 0.78, p = 0.007). The SMASH-VT (Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia) trial shows that substrate-based catheter ablation can reduce the incidence of ICD therapy in patients with a history of myocardial infarction and an ICD for secondary prevention. Reprinted with permission from Reddy et al. (15).
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Scar imaging
In 10 patients with a history of myocardial infarction who were referred for VT ablation, contrast-enhanced CMR was performed in addition to electroanatomic mapping (16). The exact location and transmural extent of scar on CMR were plotted on a color-coded 3D reconstruction of the LV. During the ablation, voltage maps of the LV were created during sinus rhythm to assess unipolar and bipolar voltage amplitude and morphology of all electrograms. A threshold of 1.54 mV for bipolar electrogram voltage yielded the best prediction of the presence of scar (receiver-operator characteristic area 0.85). Although a cutoff value of <1.5 mV for bipolar voltage resulted in a good correlation between CMR-based infarct area and mapping-based infarct area (r2 = 0.82, p < 0.0001), a mismatch of >20% in infarct area was noted in 4 of the 12 scar areas (Fig. 5). The investigators concluded that electroanatomic mapping alone may not be sufficient to exactly delineate post-infarct scar.
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Figure 5 Mismatch in Scar Delineation Between Bipolar Electroanatomic Maps and CMR Shells
(Left) CARTO bipolar electroanatomic maps. (Middle) CMR shells. (Right) Native CMR images. The top row shows underestimated inferior wall scar on the CARTO map. The bottom row shows left ventricle (LV) septal scar on the CARTO map not confirmed by CMR. On each panel, the arrows show the mismatch zone. The dotted lines represent the mitral annulus plane. Reprinted with permission from Codreanu et al. (16). Abbreviations as in Figure 3.
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Similar to the previous study, positron emission tomography (PET)/computed tomography (CT) image integration has been used to compare voltage-mapping-defined scar areas with anatomical- and metabolic-defined scar areas (17). In 14 patients undergoing VT ablation, PET/CT imaging and voltage mapping was performed. A good correlation between voltage mapping and PET imaging was found for mean LV scar area (32.6 ± 22.1 cm2 vs. 29.1 ± 24.0 cm2) and scar burden (11.7 ± 23.4% vs. 10.0 ± 21.4%). In 10 patients, the PET/CT image was integrated with the electroanatomic map. Voltage measurements showed low voltages in PET-defined scar areas (mean 0.3 ± 0.12 mV) and normal voltages in areas with normal metabolic activity (mean 7.9 ± 5.4 mV). The investigators concluded that the use of PET/CT image integration in addition to electroanatomic mapping may allow better scar identification during the mapping and ablation procedure (17). These studies suggest that additional imaging tools may be needed during VT ablation to exactly delineate the anatomical substrate. An integrated imaging approach may greatly facilitate substrate-based VT ablation.
Real-time CMR-based catheter tracking
In addition to visualization of the substrate, imaging plays an important role in guiding of the ablation catheter during the actual VT ablation procedure. In an animal (swine) study, Dukkipati et al. (18) tested a new CMR-based electrophysiology system. It allows real-time navigation of catheters throughout the cardiac chambers by using CMR-tracking microcoils embedded in the shaft of the catheters. Reformatted slice sets and 3D volume-rendered maps were used to navigate the catheters and create electroanatomic maps (Fig. 6). In 2 animals, the CMR-based system clearly provided advantage by visualizing the catheter in relation to infarcted tissue, not detected by conventional electroanatomic mapping alone. This first pre-clinical study shows that it is feasible to perform electroanatomic mapping with the use of real-time CMR tracking of catheters. Importantly, preliminary results suggest that it is also feasible to use real-time CMR catheter tracking to perform electroanatomic mapping in patients (19). Although some important challenges (mostly regarding safety, catheters, and actual ablation) still need to be overcome, this technique has great potential for catheter ablation of ischemic VT by real-time visualization of catheters in relation to scar tissue.
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Figure 6 Real-Time CMR-Based Catheter Tracking
Screen-capture images of multiple in-room displays. (A) The operator simultaneously observes a rendition of the catheter (purple line) and tracking coils (colored points) in the heart on multiple CMR plane displays and on a 3D surface-rendered view (lower left). This allows an understanding of the 3D position and orientation of the catheter in the LV. (B) A 3D myocardial DE slice set of an infarcted animal with a rendition of the catheter in close proximity to the area of scar in the anteroapical septum (yellow arrows). This allows direct visualization of scar during electroanatomic mapping. Reprinted with permission from Dukkipati et al. (18). Abbreviations as in Figures 1, 3, and 5.
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Intracardiac echocardiography
Khaykin et al. (20) reported the feasibility of the new CartoSound system (Biosense Webster) to guide VT ablation. As described earlier, this new technique can provide detailed on-line information on anatomy and function. In particular for VT ablation, the real-time assessment of LV wall motion abnormalities may be of great value. In 17 patients referred for VT ablation, a 3D map of the LV was created using a mean of 23 ± 7 contours. Based on the echocardiographic images, scar areas (thinned, akinetic, or dyskinetic areas) were identified and tagged. Afterward, a conventional point-by-point electroanatomic map was created; scar was defined as bipolar voltage <0.5 mV. Dyskinetic areas on the 3D ICE map corresponded well with scar areas identified during point-by-point mapping (Fig. 7). There was no difference in mean scar area for the 2 techniques: 3D ICE 33 ± 32 cm2 versus point-by-point map 36 ± 33 cm2 (p = NS). Subsequently, VT ablation was successfully performed in all patients under ICE guidance. This new technique may help in substrate-based VT ablation by real-time identification of wall motion abnormalities before entering the LV. However, more studies are needed to fully appreciate the role of this new technique in VT ablation.
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Figure 7 Correlation of Septal Scar Identified With ICE and Point-by-Point Mapping
A 2D intracardiac ultrasound image (left) registered as part of the CARTO shell of the LV (middle). The tip of the ICE catheter positioned in the right ventricle is seen projecting an ultrasound "fan" through the body of the LV. The red contour on the ICE image delineates an akinetic segment. The corresponding anatomical map of the LV shows the position of the akinetic segment on the mid-septum. The bipolar voltage substrate correlates well with scar identified by ICE in this patient. The cursor on the CARTO map is placed at the site of a late/fractionated potential (white arrow). The local electrogram is seen in the right panel. Reprinted with permission from Khaykin et al. (20). Abbreviations as in Figures 1, 2, and 5.
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CRT
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According to the guidelines (21), patients with drug-refractory heart failure, low LV ejection fraction, and a wide QRS complex are eligible for CRT. However, a substantial proportion of patients do not show a favorable response to CRT. It has been suggested that the assessment of LV dyssynchrony, using various imaging technologies, may improve the response rate. In the past year, new studies have provided more insight in the exact value of LV dyssynchrony assessment in the selection of patients for CRT. In addition, new imaging techniques have become available that may guide LV lead positioning.
Prediction of Response to CRT.
In the last few years, a large number of observational, single-center studies have used various echocardiographic criteria to predict a favorable response to CRT (22). The large majority of these echocardiographic parameters were related to the detection of intraventricular and/or interventricular dyssynchrony. The PROSPECT (Predictors of Response to CRT) trial is the first prospective, multicenter trial to evaluate the value of 12 different echocardiographic dyssynchrony parameters (23). A total of 426 heart failure patients (mean LV ejection fraction 23.6 ± 7.0%, mean QRS duration 163 ± 22 ms) were included. Response to CRT was defined using 2 primary outcome measures: a heart failure clinical composite score and the relative change in LV end-systolic volume at 6 months. Overall, 294 (69%) patients had a clinical improvement and 161 (56%) patients showed echocardiographic improvement after CRT. High intraobserver and interobserver variability was noted for some tissue Doppler imaging–derived parameters, and for the M-mode–derived septal-to-posterior wall motion delay. Moreover, the predictive value of the echocardiographic dyssynchrony parameters for response to CRT was modest. The disappointing results of this trial are related to various factors, including training and education (to reduce intraobserver and interobserver variability), technical issues, and pathophysiological issues.
From a technical point of view, more accurate approaches may be needed for assessment of LV dyssynchrony. It has been suggested that the combination of longitudinal and radial dyssynchrony may provide superior prediction of response to CRT; indeed, the combination yielded a sensitivity of 88% with a specificity of 80% in 190 heart failure patients undergoing CRT, which was significantly better than using either technique alone (p < 0.0001) (24). Also, novel speckle tracking strain analysis may contribute to a better selection of CRT candidates. This technique enables an easier and more accurate and comprehensive assessment of LV dyssynchrony (Fig. 8). In 161 patients, speckle tracking echocardiography was used to predict echocardiographic response (decrease in LV end-systolic volume  15%) to CRT (25). A cutoff value of radial dyssynchrony 130 ms was able to predict response to CRT with a sensitivity of 83% and a specificity of 80%. Interestingly, only patients who showed a favorable response to CRT had a significant reduction in LV dyssynchrony at follow-up (from 251 ± 138 ms to 98 ± 92 ms; p < 0.001). Finally, Lim et al. (26) recently proposed a new parameter for LV dyssynchrony that may better predict a favorable response to CRT. The strain delay index, which is defined as the sum of the difference between longitudinal peak and end-systolic strain across 16 segments, was assessed in 100 heart failure patients using speckle tracking echocardiography. The strain delay index was significantly larger in CRT responders than nonresponders (35 ± 7% vs. 19 ± 6%, p < 0.001), and was closely correlated with reverse remodeling in patients with both ischemic and nonischemic cardiomyopathy (r = –0.68, p < 0.001, and r = –0.71, p < 0.0001, respectively). The optimal cutoff value to predict response to CRT was a strain delay index 25% (sensitivity 95%, specificity 83%) (26).
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Figure 8 2D Speckle-Tracking Strain Imaging
In the left panels, 2D strain images are shown. The arrows depict the type of deformation assessed in each view: radial thickening (A), circumferential shortening (B), and longitudinal shortening (C). The middle and right panels show the segmental time-strain curves for a synchronous (middle panels) and dyssynchronous (right panels) LV for each view. Time differences in peak-systolic strain (t) between the anteroseptal (AS) and posterior (P) segments in the short-axis view, and between basal-septal (BS) and basal-lateral (BL) segments in the 4-chamber view, can be obtained from these curves. Reprinted with permission from Delgado et al. (25). Abbreviations as in Figures 1 and 5.
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From a pathophysiology point of view, it was previously shown that extensive scar tissue may limit response to CRT. The precise location of the LV pacing lead, however, may also be important. Recently, it has been suggested that a concordance in LV lead position and site of latest mechanical activation is associated with a better outcome after CRT (27). In 244 patients, the site of latest activation was determined using speckle tracking echocardiography, and LV lead position was reviewed from chest radiographs. In patients with a concordant LV lead position (n = 153, 63%), a significant reduction in LV end-systolic volume was noted (from 189 ± 83 ml to 134 ± 71 ml, p < 0.001), whereas in patients with a discordant LV lead position no change in LV end-systolic volume was noted (from 172 ± 61 ml to 162 ± 63 ml, p = NS). Importantly, at long-term follow-up (32 ± 16 months), patients with a concordant LV lead position had a better event-free survival as compared with patients with a discordant LV lead position (Fig. 9).
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Figure 9 Survival and Event Curves After CRT According to LV Lead Position
(A) Hospitalizations for heart failure. (B) Survival. (C) Event-free survival including death, heart transplantation, and hospitalization for heart failure. Patients with an LV lead positioned at the site of latest activation have a better response to CRT and a better prognosis at long-term follow-up as compared with patients with a discordant LV lead position. Reprinted with permission from Ypenburg et al. (27). CRT = cardiac resynchronization therapy; other abbreviation as in Figure 5.
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Imaging During CRT Implantation.
During LV lead implantation, the electrophysiologist can encounter difficulties with positioning of the lead because of variations in the cardiac venous system. It has been shown that MSCT is of great value for pre-procedural evaluation of coronary venous anatomy. In addition, MSCT can also provide important information on the course of the phrenic nerves in relation to the target veins (28).
During the implantation procedure, conventional angiography is most frequently used. New rotational angiography offers a multiangle, 3D dynamic view on the coronary veins, and may provide more detailed information on diameter, take-off, and tortuosity of the various branches. Blendea et al. (29) used rotational angiography in 51 patients referred for CRT implantation to evaluate cardiac venous anatomy. In 44 patients (86%), the angiograms were of sufficient quality to study the complete venous system. The great cardiac vein, posterior vein, and lateral vein were observed in 100%, 76%, and 91% of the patients, respectively. Of interest, lateral veins were less frequently observed in patients with a history of a lateral infarction as compared with patients without myocardial infarction (33% vs. 96%, p < 0.05). Although no head-to-head comparison with conventional angiography was performed, this study suggests that rotational angiography may be a valuable tool for depicting coronary venous anatomy during LV lead implantation procedures.
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Conclusions
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In the past year, numerous studies have further strengthened the close relationship between imaging and electrophysiology. New imaging techniques and image integration strategies have been introduced to guide AF ablation. Dedicated imaging techniques have provided more insight into the effects of catheter ablation on LA function. In addition, studies from the past year emphasize the important role of imaging in prediction of the occurrence and inducibility of VT. The correlation between anatomical findings and arrhythmogenic substrate in VT ablation requires further elucidation. The response to CRT has been further evaluated, and the relative merit of LV dyssynchrony in CRT still is not clear.
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Footnotes
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Dr. Bax receives grants from Medtronic, Boston Scientific, BMS Medical Imaging, St. Jude Medical, GE Healthcare, and Edwards Lifesciences.
* Reprint requests and correspondence: Dr. Jeroen J. Bax, Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, 2333 ZA Leiden, the Netherlands (Email: j.j.bax{at}lumc.nl).
Manuscript received November 5, 2008;
revised manuscript received December 4, 2008,
accepted December 19, 2008.
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