Heart failure
Emerging Role of Myocardial Perfusion Imaging to Evaluate Patients for Cardiac Resynchronization Therapy

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Left ventricular (LV) dyssynchrony is an increasingly important consideration in the evaluation and management of patients with LV systolic dysfunction. Improvements in clinical status, LV remodeling, and survival have been demonstrated with the use of cardiac resynchronization therapy (CRT). The current selection criteria for patients who undergo CRT include the presence of severe LV dysfunction, significant heart failure symptoms, and electrical dyssynchrony on surface electrocardiography (wide QRS interval). However, up to 40% of patients who undergo CRT do not experience reductions in symptoms or LV functional improvement. Because electrical dyssynchrony is not synonymous with contractile or mechanical dyssynchrony, efforts have been made to more accurately quantify mechanical dyssynchrony in the hope of improving the selection of patients for CRT. These efforts have focused largely on echocardiographic measures of mechanical dyssynchrony. A novel method to quantify LV mechanical dyssynchrony has been developed using phase analysis of gated single photon-emission computed tomographic myocardial perfusion imaging. In conclusion, this report describes potential advantages, compared with other methods, of using myocardial perfusion imaging to evaluate patients for CRT; reviews the method of the phase analysis technique to quantify dyssynchrony; reviews the available evidence of its utility; and describes future directions in research.

Section snippets

Myocardial Perfusion and Response to Cardiac Resynchronization Therapy

One potential explanation for eligible patients failing to respond to CRT is the presence, degree, and location of myocardial scar tissue. This has been investigated in several studies using MRI and SPECT imaging.19, 20, 21 The effect of regional posterolateral scar tissue on response to CRT was assessed in 40 patients with traditional indications for CRT. The presence or absence of ≥50% transmural scar in the posterolateral wall was related to CRT response rate (14% vs 81%, p <0.05).19

Indexes

Method of Phase Analysis

A method to extract phase (representing the timing of the onset of mechanical contraction) from regional LV count changes obtained during gated SPECT myocardial perfusion imaging has been developed and incorporated into a clinical application to quantify dyssynchrony.12 Three-dimensional count distributions are extracted from each of the 8 LV short-axis data sets and submitted to Fourier phase analysis. The analysis applies 1-dimensional fast-Fourier transform to the count variation over time

Temporal Resolution

Most gated SPECT imaging is performed at 8 frames/cardiac cycle. This increases counts per frame and improves image quality. This implies a limited temporal resolution of gated SPECT imaging to quantify the timing of the onset of myocardial contraction. However, because the discrete points of the time-activity curves are transformed into continuous thickening functions using fast-Fourier transformation, the actual temporal resolution is much higher than 8 frames/cardiac cycle. The temporal

Reproducibility

The recently reported results of the PROSPECT trial brought attention to the need for a diagnostic test to be reproducible to be appropriately and widely applied in the clinical evaluation of dyssynchrony.6 Because of its automation, the phase analysis of gated SPECT perfusion imaging has inherent advantages that enhance reproducibility. The variability of phase analysis has been shown to be low in a cohort of 100 subjects (50 normal controls and 50 patients with LV EFs ≤35%), with a

Electrical Versus Mechanical Dyssynchrony

Electrical dyssynchrony is usually defined as a QRS duration ≥120 ms, and this is the currently accepted dyssynchrony criterion in patients with significant HF to be considered for CRT. In echocardiographic studies, there were relatively weak correlations between electrical and mechanical dyssynchrony.22 Similarly, the relation between electrical and mechanical dyssynchrony as defined by phase analysis of gated SPECT imaging was investigated in 125 patients with LV EFs ≤35%. Although patients

Phase Analysis in the Quantification of Dyssynchrony

Phase analysis of gated SPECT imaging has been used in several studies to demonstrate its ability to quantify mechanical dyssynchrony.15, 16, 17 Phase analyses were compared between several cohorts of patients expected to have higher degrees of dyssynchrony than normal controls. The phase SD was shown to be significantly higher in patients with LV EFs ≤40% compared with normal controls (47.8° vs. 15.7°, p <0.001). Similarly, the phase SD was significantly higher in patients with normal EFs but

Phase Analysis and Prediction of Response to Cardiac Resynchronization Therapy

Perhaps the most important study to date using phase analysis of gated SPECT perfusion imaging evaluated the ability of phase analysis to predict patient response to CRT. This was done in a single-center pilot study of 42 patients with traditional indications for CRT. The phase SD was significantly higher in those who responded to CRT than in those who did not respond to CRT (56.3° ± 19.9° vs 37.1° ± 14.4°, p <0.01). Furthermore, receiver-operating characteristic curve analysis of phase SD

Prevalence of Dyssynchrony

The prevalence of significant dyssynchrony as defined by a phase SD >43° was evaluated in 99 patients with mild to moderate LV dysfunction (EF 35% to 50%) and in 175 patients with severe LV dysfunction (EF ≤35%). The prevalence of significant dyssynchrony was determined to be 37% in patients with mild to moderate LV dysfunction and 62% in patients with severe LV dysfunction.24

Discussion

The use of myocardial perfusion imaging to evaluate patients for CRT offers several potential advantages. The automated nature of the technology lends itself to inherently high levels of reproducibility, which will be critical for the widespread application of dyssynchrony imaging.6, 14 Second, the technology affords a truly 3-dimensional and global assessment of LV dyssynchrony. Phase analysis calculates data from approximately 600 regions of the left ventricle. This is in contrast to tissue

Conclusion

Gated SPECT myocardial perfusion imaging has the ability to reproducibly quantify myocardial perfusion and LV dyssynchrony on a 3-dimensional and global basis. High degrees of myocardial scar or posterolateral scar may prevent patient response to CRT, whereas increased degrees of mechanical dyssynchrony suggest an increased likelihood of responding to CRT. Future work will need to be done to explore the potential to integrate myocardial perfusion information, along with the location, severity,

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      By contrast, the absence of significant mechanical dyssynchrony appears to be associated with a high rate of non-response to CRT.8–11 The use of phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the evaluation of mechanical dyssynchrony has been described in previous studies.12–15 Standard gated SPECT short-axis imaging enables detection of three-dimensional regional maximal counts for each time frame.

    • Concordant Versus Discordant Left Bundle Branch Block in Heart Failure Patients: Novel Clinical Value of an Old Electrocardiographic Diagnosis

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    Conflicts of interest: Dr. Garcia has an ownership interest in and serves as a consultant and advisory board member for Syntermed, Inc., Atlanta, Georgia. Dr. Garcia also receives royalties from the sale of clinical software that was used as part of this research. Dr. Borges-Neto and Dr. Trimble have received research support from the Duke-Medtronic Strategic Alliance, which funded some of the studies reviewed in this report.

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