Nonechocardiographic Imaging in Evaluation for Cardiac Resynchronization Therapy
2011; Lippincott Williams & Wilkins; Volume: 4; Issue: 3 Linguagem: Inglês
10.1161/circimaging.111.963504
ISSN1942-0080
AutoresWael AlJaroudi, Ji Chen, Wael A. Jaber, Steven G. Lloyd, Manuel D. Cerqueira, Thomas H. Marwick,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoHomeCirculation: Cardiovascular ImagingVol. 4, No. 3Nonechocardiographic Imaging in Evaluation for Cardiac Resynchronization Therapy Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBNonechocardiographic Imaging in Evaluation for Cardiac Resynchronization Therapy Wael AlJaroudi, MD, Ji Chen, PhD, Wael A. Jaber, MD, Steven G. Lloyd, MD, PhD, Manuel D. Cerqueira, MD and Thomas Marwick, MD, PhD Wael AlJaroudiWael AlJaroudi From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). , Ji ChenJi Chen From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). , Wael A. JaberWael A. Jaber From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). , Steven G. LloydSteven G. Lloyd From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). , Manuel D. CerqueiraManuel D. Cerqueira From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). and Thomas MarwickThomas Marwick From the Department of Cardiovascular Medicine, Section of Imaging, Cleveland Clinic, Cleveland, OH (W.A., W.A.J., M.D.C., T.M.); Department of Radiology, Emory University, Atlanta, GA (J.C.); and Department of Cardiovascular Disease, University of Alabama at Birmingham, AL (S.G.L.). Originally published1 May 2011https://doi.org/10.1161/CIRCIMAGING.111.963504Circulation: Cardiovascular Imaging. 2011;4:334–343IntroductionIn patients with heart failure and prolonged QRS duration, randomized clinical trials have shown that cardiac resynchronization therapy (CRT) is associated with improvement in quality of life, left ventricular (LV) remodeling, and survival.1–3 The improvements are believed to be mediated by more effective synchronized contraction in the presence of a wide QRS, but mechanical and electrical dyssynchrony are not equivalent.4,5 Although the concept of CRT response remains problematic,6 20% to 40% of patients who receive CRT based on electrical dyssynchrony criteria (ie, QRS duration) do not derive symptom improvement or demonstrate reverse remodeling.7–10 Scar burden11–13 and failure to place the LV pacing lead at the site of latest onset of contraction14–17 have been linked to a poor response. Thus, optimal clinical decision-making for CRT must include a comprehensive evaluation of all these factors to identify patients with heart failure who will benefit.The standard echocardiographic parameters of LV mechanical dyssynchrony have been extensively reviewed,18 with >600 published articles. Most of this work has been done using tissue Doppler imaging, with more recent work using speckle tracking,19,20 3D echocardiography,21 echocardiographic contrast imaging,22 and intracardiac echocardiography.23 Despite the important benefits of high temporal resolution, success in individual centers, and ability to assess the impact of scar burden and concordance of LV lead with latest activation site,14 fundamental limitations of tissue Doppler imaging include the inability to measure over a sufficient number of cardiac cycles to overcome beat-to-beat variation, poor image quality, and measurement error.24 In the only randomized trial of CRT in patients with wide QRS,25 the failure of 12 different echocardiographic dyssynchrony parameters to improve outcome was most likely related to the large interobserver and intraobserver variability (4% to 24% and 7% to 72%, respectively). These limitations of echocardiography have led to a search for nonechocardiographic imaging techniques to optimize decision-making before CRT (Table 1).Table 1. Comparison of Different Imaging Modalities of CRTEchocardiographyCCTCMRSPECTTechnical characteristics Reproducibility++++++++++ Temporal resolution, ms20–3060–16520–4015–45 Spatial resolution++++++++++ Contrast-to-noise ratio+++++++++++ Automated software+++++++++ Simple to use++++++++ Time for analysis, min≈10–15≈10–15≈45–60≈1–3 No. of data points16-segment model540 data points16–600>600 data points 3D data3D TTEYesYesYes Affected by R-R interval variability++++++++ Performed post hoc on prior studiesProper frame rateProspective gatingTagged sequenceAt least 8 frames/cycle Ionizing radiationNoYesNoYes Availability++++++++++ Cost$$$$$$$$ Fusion of modalitiesIn evolutionYes with PET/SPECTYes with SPECTYes with CT and CMRClinical utilities Scar burden++ (strain)+++++++++ LVEF volumes+++++++++++++ RV volumes++ (3D)++++− Mitral regurgitation++++++− Simplicity of interpretation, no. indices>161–3≈5–72 Latest site of activation, regional++++++++++ Coronary vein−+++++− Post-CRT follow-up+++++−+++ Clinical experience++++++++++CCT indicates cardiac CT; CMR, cardiac MRI; CRT, cardiac resynchronization therapy; LVEF, left ventricular ejection fraction; SPECT, single-photon emission CT; TTE, transthoracic echocardiogram; RV, right ventricle.Cardiac CTThe role of cardiac CT (CCT) in heart failure has been reviewed recently.26 The technique assesses scar location and burden,27 anatomic location of the phrenic nerve, cardiac venous anatomy,28 LV function, and dyssynchrony indices5 (Table 1, Figure 1).Download figureDownload PowerPointFigure 1. Nonechocardiographic imaging of CRT. A-J, Scar burden, LV function, and mechanical dyssynchrony are visualized with different imaging modalities. A and B, A large area of delayed enhancement (scar) (arrow) by cardiac CT (CCT) and cardiac MRI (CMR), respectively. C, A polar map of an at-rest myocardial perfusion image showing large, fixed perfusion defect size. D-F, Quantification of LV volumes and EF with CCT, CMR, and gated single-photon emission CT, respectively. G, The method of assessing mechanical dyssynchrony with CCT using time to maximal LV wall thickening curves. Reprinted with permission from Truong et al.5H, Tagged CMR, which is used to derive strain and dyssynchrony indices. I and J, Phase histogram and polar map showing segmental onset of mechanical activation with LV site of latest activation (star, inferior wall), respectively. K, A 3D volume-rendered image of the coronary venous anatomy by CCT while planning LV lead placement. *Side branches of the posterior vein of the left ventricle. Reprinted with permission from Van de Veire et al.28L, A reconstructed 3D CMR image showing the coronary sinus. CS indicates coronary sinus; CX, left circumflex coronary artery; EF, ejection fraction; GCV, great cardiac vein; LMV, left marginal vein; LV, left ventricle; PIV, posterior interventricular vein; PVLV, posterior vein of the left ventricle; RCA, right coronary artery; SCV, superior cardiac vein.Scar Location and BurdenThe role of CCT in assessing scar burden is increasing but still faces many challenges. Dual-phase evaluation has been shown to detect scar after acute and chronic myocardial infarction29,30 (Figure 1A) and correlates well with gadolinium delayed enhancement with cardiac MRI (CMR), although the contrast-to-noise ratio is far superior with CMR.31 However, there are no published studies that evaluated the impact of scar burden by CCT on CRT response.Coronary Venous AnatomyCCT has an advantage over other techniques in the assessment of the coronary venous system (Figure 1K) that correlates well with conventional catheter-based venography (r=0.82 to 0.95)28,32 and can register venous anatomy to the site of latest activation.33 This is particularly important because LV lead placement for CRT is technically challenging in dilated ventricles with prominent tortuosity, stenosis, and acute angulation of the coronary veins28,34 and especially so in the 5% of subjects in whom the posterior vein of the LV is absent and the 39% among whom the left-side marginal vein is absent.35 In addition, CCT identifies the relationship of the left-side phrenic neurovascular bundle to the target vein, which allows the operator to avoid diaphragmatic stimulation.36Mechanical Dyssynchrony and CRT ResponseLittle work has been done on mechanical dyssynchrony indices with CCT, with no published data on prediction of CRT response. Recently, 3 global indices have been described in a small study (N=38) using the following 3 parameters (Figure 1G): (1) SD of the time from the R wave to maximal wall thickness (computed as the radial distance between the endocardial and epicardial borders) (≈540 data points per patient), (2) SD of time to maximal wall motion (using the endocardial borders and centerline algorithm) (≈480 data points), and (3) SD of time to minimal systolic area (≈90 data points). For segmental dyssynchrony, the average of the maximal difference in time to maximal wall thickness or wall motion among the 3 pairs of opposing walls were derived (average, 180 and 160 data points per patient, respectively). Overall, the reproducibility of global dyssynchrony was much better than regional parameters (intraclass correlation coefficient range, 0.71 to 0.95 versus 0.06 to 0.91, respectively). Among the global indices, the SD based on time to maximal wall thickening was the most reproducible (intraobserver and interobserver reproducibility, 0.95 and 0.94, respectively; P 65 ms) Radial dyssynchrony (tissue synchronization index)SN, 90%; SP, 59% (n=40) (septal-lateral delay) Could not further stratify patients (radial dyssynchrony) (n=225)Phase contrast MR-TVMTissue velocity mapping3D velocity information per pixelVelocities used to derive strainMeasures interventricular dyssynchronySimilar to above Long scan time to acquire imagesRespiratory artifactAorta-pulmonary onset flow time difference for interventricular dyssynchrony (RV-LV) (milliseconds)No studies DENSEEncodes position/tissue displacementBetter image contrast than MR-TVMUsed to derive strainLow temporal resolution (1 image/cardiac cycle) Not widely availableN/ANo studiesTagged imaging SPAMMSPAMMDeformation is quantified into strainLong processing time (up to several days) Low spatial resolution (5–7 mm)Tagging fades in diastoleCircumferential strain (SD of time to peak systolic strain)Regional variance of strainRegional variance of vector strainTemporal uniformity index (circumferential uniformity ratio estimate)PPV, 87% NPV, 100% to improve patient selection (circumferential uniformity ratio estimate) (n=47) CSPAMMSubtraction of 2 out of phase tagging grids to give improved persistence of tag linesTags last longer in diastoleLonger acquisition time Reduced temporal resolutionHARPAnalysis of tagged images in the frequency domainAutomated "Faster" 2D and 3D HARPUp to 45 min processing timeSENCSinusoidal tags applied in the slice planeFastest postprocessing Instantaneous real-time quantitative strainHigher spatial resolution Through-plane encoding allows circumferential and longitudinal strainNot widely available Analysis is complexCMR indicates cardiac MRI; CRT, cardiac resynchronization therapy; CSPAMM, complementary spatial modulation of magnetization; DENSE, displacement encoding with stimulated echoes; HARP, harmonic phase analysis; LV, left ventricle; MR-TVM, magnetic resonance tissue velocity mapping; N/A, not applicable; NPV, negative predictive value; PPV, positive predictive value; RV, right ventricle; SENC, strain-encoded MRI; SN, sensitivity; SP, specificity; SPAMM, spatial modulation of magnetization; SSFP, steady-state free precession.ChallengesThe broad use of CMR to plan CRT still faces many challenges. There are problems with imaging patients with implanted devices, although this has been recently attempted in well-selected and monitored patients on a case-by-case basis68,69; however, the resultant artifact remains a major challenge when analyzing dyssynchrony and response after CRT38 (Figure 3). Furthermore, despite recent advances,70 the analysis process, including use of specialized software, is still complicated, time consuming, and not fully automated. Like other imaging modalities used in CRT studies, data have been validated in very small cohorts with different indices. Lastly, access to CMR may be limited because in many areas, it often is performed only in large centers. Even when available, not all centers have expertise in the interpretation of synchrony.Download figureDownload PowerPointFigure 3. Implantable cardiac device and ventricular lead artifact by cardiac MRI. The figure illustrates the artifacts (arrows) that are produced by an implantable cardiac device and ventricular lead in a well-selected and monitored patient who underwent cardiac MRI. Can indicates signal void artifact with no image (only black region) near the subcutaneously implanted pulse generator can. Reprinted with permission from Lardo et al.38Nuclear ImagingThe role of nuclear imaging with gated SPECT MPI in CRT has been recently reviewed and described as a "one-stop shop" to predict CRT response. It provides data on scar burden and location, LV function, LV site of latest contraction, and mechanical dyssynchrony from a single scan71–74 (Figure 1).Scar Burden, Location, and Response to CRTThe presence, location, and burden of myocardial scar have been shown to affect response to CRT.71,75 In a study by Adelstein et al,11 an inverse relationship was described between the extent of fixed perfusion defect on MPI and absolute or relative increase in LVEF 6 months after CRT (r=−0.63 and −.53, respectively, P<0.01) (n=50). Furthermore, patients who responded to CRT had lower global scar burden and scar density near the LV lead versus nonresponders.11,15 Additionally, the extent of scar around the LV lead correlates negatively with improvement in LVEF,11 and is associated with no response in 29% of patients with extensive scar at the LV lead site despite having a concordant lead with latest site of activation.15 Similar findings showed that a transmural scar (<50% tracer activity) at the site of LV lead placement was associated with no response to CRT.13 These results are concordant with CMR studies as described in the previous section. An advantage of SPECT MPI is the ability to automatically quantify the scar burden with good reproducibility.76 However, the low spatial resolution and counts of the images remains a limitation, particularly when assessing viability in dilated ventricles with thin walls because it might overestimate the extent of scar. PET imaging is performed with higher tracer counts, lower radiation exposure, and better spatial resolution, solving the problem to a great extent.77 However, there are limited data on dyssynchrony or CRT response using PET images.Coronary Venous AnatomySPECT MPI plays no role in identifying coronary venous anatomy.Mechanical DyssynchronyTechnique CharacteristicsNuclear imaging was used to evaluate mechanical dyssynchrony several decades ago in the era of gated equilibrium radionuclide angiography.78–81 In recent times, gated SPECT has quickly emerged as an attractive alternative to quantify dyssynchrony82 (Figure 1). The technique of phase analysis for SPECT MPI has been described extensively by Chen et al71,82 using the Emory Tool Box (SyncTool; Emory University; Atlanta, GA), with other software in development.83 Briefly, a 3D count distribution is extracted from each of the LV short-axis data sets; a 1D fast Fourier transform is applied to the count variation over time for each voxel, generating a 3D phase distribution that describes the timing of LV onset of mechanical contraction over the entire R-R cycle (Figure 1I). Two clinically relevant dyssynchrony indices are derived: SD and histogram bandwidth.82 The normal values have been published and validated.82,84,85 The technique is fully automated, has effective temporal resolution of ≈15 ms for a heart rate of 60 beats/min,86 interobserver and intraobserver reproducibility of 99%,87 and high repeatability88 independent of the type of camera used,89 the type of image reconstruction,90 or the tracer dose91 (Table 1).Dyssynchrony, LV Lead Placement, and CRT ResponseAlthough mechanical dyssynchrony is associated with the extent of cardiomyopathy (P=0.01), scar burden (P 120 ms, and LVEF 43°) in patients with severe (LVEF, 1 year and showed no end point outcomes (cardiac death, heart failure hospitalization, shocks, CRT deactivation). Bottom, nonresponder to CRT. The patient had baseline LV dyssynchrony but no scar. The latest activation site was at the inferolateral wall; however, the LV pacing lead was placed at the anteroseptal wall. The patient had deteriorated LV dyssynchrony immediately after CRT. This patient had CRT deactivation due to worsened symptoms 15 days after CRT. CRT indicates cardiac resynchronization therapy; LV, left ventricle; PHB, phase histogram bandwidth; PSD, phase standard deviation.The change of dyssynchrony parameters after CRT occurs immediately after implantation, and may predict long-term LV remodeling.94 It would therefore be possible, using gated SPECT with single-tracer injection, to change CRT parameters to optimize response, especially with the excellent repeatability of the technique to measure dyssynchrony.88ChallengesThe major challenges with gated SPECT for CRT are the radiation burden with serial scans when assessing LV remodeling and improvement in dyssynchrony indices after therapy and the inability to visualize coronary venous anatomy, although the fusion of SPECT-CT imaging could potentially address the latter issue.Future DirectionsThe search for the best modality for noninvasive cardiac imaging to predict CRT response is still ongoing. The different modalities bring different strengths and weaknesses to this process (Table 1). A universal first step should be to assess LV function; whereas CMR is the gold standard, other imaging modalities, including 3D echocardiography with contrast, provide reliable LVEF. It is important to realize that the prognostic benefit of CRT is not based on the prediction of response (itself a controversial topic), but in some circumstances, prediction of symptomatic response may be the main consideration driving the decision to implant a device. The identification of significant mechanical dyssynchrony may be performed by detection of the site of latest activation by SPECT or echocardiography with speckle tracking. In patients with ischemic heart disease, CMR is the gold standard for scar quantification, but SPECT is a good alternative. Finally, CCT could be used to assess coronary venous anatomy in selected patients. Further multicenter studies that evaluate all modalities together or an integrative approach displaying anatomy and function are needed to define which single test or combination of techniques can best guide initial patient selection, procedural approach, and postimplant optimization.AcknowledgmentsWe thank Michael Ridner, MD, from the Heart Center at Huntsville for providing Figure 1A; Prem Soman, MD, PhD, from the University of Pittsburgh Medical Center for providing patient examples in Figures 1I, 1J, and 6; and Thomas S. Denney, PhD, and Bharath Ambale Venkatesh, PhD, from Auburn University for providing Figure 2.DisclosuresDr Chen receives research funding from the National Institutes of Health (1R01HL094438; principal investigator, Ji Chen, PhD) and royalties from the sale of the Emory Cardiac Toolbox with SyncTool. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest practice.FootnotesCorrespondence to Wael AlJaroudi, MD, Sydell and Arnold Miller Family, Heart and Vascular Institute, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, 9500 Euclid Ave/J1–5, Cleveland, OH 44195. E-mail [email protected]orgReferences1. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004; 350:2140–2150.CrossrefMedlineGoogle Scholar2. Cleland JG, Calvert MJ, Verboven Y, Freemantle N. Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J. 2009; 157:457–466.CrossrefMedlineGoogle Scholar3. 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