Indian Journal of Nuclear Medicine

: 2019  |  Volume : 34  |  Issue : 2  |  Page : 88--95

Equilibrium radionuclide angiography in evaluation of left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy: Comparison with electrocardiographic parameters and speckle-tracking echocardiography

Abhinav Singhal1, Bangkim Chandra Khangembam1, Sandeep Seth2, Chetan Patel3,  
1 Department of Nuclear Medicine, Institute of Liver and Biliary Sciences; Department of Nuclear Medicine, Cardiothoracic Centre, All India Institute of Medical Sciences, New Delhi, India
2 Department of Cardiology, Cardiothoracic Centre, All India Institute of Medical Sciences, New Delhi, India
3 Department of Nuclear Medicine, Cardiothoracic Centre, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Dr. Chetan Patel
Department of Nuclear Medicine, Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 049


Purpose of the Study: The purpose of this study was to study the role of equilibrium radionuclide angiography (ERNA) in the assessment of left ventricular (LV) mechanical dyssynchrony in patients with dilated cardiomyopathy (DCM), by correlating the findings with electrocardiographic parameters and speckle-tracking echocardiography (STE). Methods: This was a prospective observational study. A total of 55 patients with a mean age 42.5 ± 11 years (range: 19–61 years) diagnosed with DCM underwent ERNA and echocardiography sequentially. On ERNA, phase images of LV were obtained, and standard deviation of LV mean phase angle (SD LVmPA) was derived to quantify intra-LV mechanical dyssynchrony (ILVD). Similarly, on STE, “dyssynchrony index” was calculated as the standard deviation of time-to-peak systolic circumferential strain (SDCS) of the six mid-LV segments. The cutoff values used to define mechanical dyssynchrony were SD LVmPA >13.2° (or >27.1 ms) and SDCS >74 ms on ERNA and STE, respectively. The results obtained from the two modalities were then compared. Results: Speckle-tracking analysis could be done on the echocardiographic data of only 42 patients. Paired data from ERNA and STE studies of these 42 patients (26 males and 16 females) were compared, which showed no significant difference in the detection of ILVD (P = 0.125). The two modalities showed good agreement with Cohen's kappa value of 0.78 (P < 0.0001). SD LVmPA and SDCS values showed moderately strong linear correlation (ρ = 0.69; P < 0.0001). No significant association of mechanical dyssynchrony on ERNA or STE was found with QRS duration and with the presence or absence of left bundle branch block. ILVD was also found to be negatively correlated with LV ejection fraction. Conclusion: ERNA is comparable to STE for the assessment of LV mechanical dyssynchrony.

How to cite this article:
Singhal A, Khangembam BC, Seth S, Patel C. Equilibrium radionuclide angiography in evaluation of left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy: Comparison with electrocardiographic parameters and speckle-tracking echocardiography.Indian J Nucl Med 2019;34:88-95

How to cite this URL:
Singhal A, Khangembam BC, Seth S, Patel C. Equilibrium radionuclide angiography in evaluation of left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy: Comparison with electrocardiographic parameters and speckle-tracking echocardiography. Indian J Nucl Med [serial online] 2019 [cited 2019 Jun 19 ];34:88-95
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Cardiac resynchronization therapy (CRT) has now become the standard of care for drug refractory heart failure patients.[1],[2] The current clinical guidelines mainly rely on QRS duration derived from electrocardiogram (ECG) for the selection of patients for CRT, with wide QRS morphology (>120 ms) being regarded as an essential criterion.[3] However, even after following the guidelines, 20%–30% of patients fail to respond to CRT.[4],[5],[6] Owing to the high cost of CRT implantation and possible procedural complications, it is imperative to search for parameters which can predict response to CRT with better accuracy.

The presence of ventricular contractile dyssynchrony is theoretically considered an essential substrate, which could be corrected by CRT, leading to clinical improvement. Conventionally, wide QRS duration has been presumed to be a surrogate for mechanical dyssynchrony of contractile function. However, subsequent research has pointed that a wide QRS complex may just be a marker of electrical dyssynchrony and may not accurately reflect the mechanical dyssynchrony.[7] Emphasis has been given to indentify the cardiac mechanical dyssynchrony, which may be a better predictor of response to device therapy.[8],[9],[10] Various imaging techniques have been used to measure mechanical dyssynchrony and response to CRT. These include echocardiography, cardiac magnetic resonance, equilibrium radionuclide angiography (ERNA), and gated myocardial perfusion single-photon emission computed tomography.[8],[9],[10],[11],[12],[13],[14],[15],[16]

Echocardiography has been used most commonly for this purpose as cardiologists are most familiar with this method. Different echocardiography-derived dyssynchrony parameters have evolved over time, with the tissue Doppler imaging (TDI) being the most widely used technique. However, echocardiography is largely operator dependent, so reproducibility is limited. Moreover, data from PROSPECT trial do not support the use of echocardiography-derived dyssynchrony parameters (including TDI) to be used in routine clinical practice.[15] Speckle-tracking echocardiography (STE) is another novel technique which has shown promise in the post-PROSPECT era; however, the search for a more reproducible method of measuring left ventricular (LV) mechanical dyssynchrony continues.

ERNA is a well-established imaging modality to assess ventricular function and wall motion.[17] Using phase analysis, ERNA has also been investigated for the assessment of dyssynchronous cardiac contraction, and it is proven to be highly reproducible.[18],[19],[20],[21] Being noninvasive, highly reproducible, and relatively easy to perform, it may be one of the most promising techniques to quantify dyssynchrony.

The primary objective of our study was to evaluate ERNA in the assessment of mechanical cardiac dyssynchrony in patients of dilated cardiomyopathy (DCM) and compare its results with STE. The secondary objectives were to test the association of mechanical synchrony parameters derived on ERNA and STE with ECG parameters of QRS duration and morphology.


Fifty-five patients with DCM with low ejection fraction (≤40%) were recruited in the study. Inclusion criteria were (1) clinical heart failure with LV ejection fraction (LVEF) ≤40%, (2) duration of symptoms >1 year, (3) age >12 years, and (4) sinus rhythm. Patients with a history of valvular heart disease and arrhythmias were excluded. ERNA study was successfully performed in all 55 patients. However, satisfactory echocardiographic images required for speckle-tracking analysis could not be obtained in 13 patients, due to lack of proper acoustic window for imaging. Thus, 42 STE studies were available for comparison with ERNA.

Equilibrium radionuclide angiography acquisition and processing

ERNA studies were done at rest with in vivo red blood cell labeling with intravenous administration of 0.5–0.9 mg (15 μg/kg of body weight) of stannous chloride, followed 10–15 min later by 15–20 mCi (550–740 MBq) of technetium-99m pertechnetate. Acquisition was started 10–15 min later with a dual-head gamma camera (Infinia Hawkeye 4; GE Medical Systems, Waukesha, WI, USA) fitted with a low-energy general purpose collimator. Images were acquired in left anterior oblique view (best septal view). The projection was gated with the ECG to get 32 frames spanning the cardiac cycle. Images were acquired in 64 × 64 matrix, with a zoom factor of 1.6; each view acquired for approximately 500–600 kilo counts. The ECG was monitored continuously to ensure R-wave gating of the QRS complex. Elimination of ventricular premature beats was obtained with a window threshold of 20% around the mean R–R interval during acquisition of projections.

Images were analyzed using commercial software (XT-ERNA; GE Medical Systems, Waukesha, WI, USA). Count-based LVEF was then computed using semiautomatic regions of interest (ROI) on two separate regions (end diastolic and end systolic). ROI were drawn automatically by the computer with adjustments of border definition performed by the observer blinded to the state of conduction. Phase images are computed using the first harmonic Fourier transform to display the mechanical contraction time for all the ventricular pixels of the image during one composite cardiac cycle.

Phase image shows the areas of the heart whose change in activity, on a pixel-by-pixel basis, occurs at the same time. This, in effect, shows the progression of mechanical systole through the heart over the R–R interval giving information about the relative timing of contraction of cardiac pixels, that is, the synchronicity. Phase images were generated for cardiac regions using a continuous color scale, corresponding to phase angles from 0° to 360°. From these histograms representing the distribution of the pixels for each ventricle according to their phases, the mean phase and its standard deviation were calculated [Figure 1]. Mean phase angle (mPA) was computed for LV blood pool as the arithmetic mean of the phase angle for all pixels in the corresponding ventricular ROI. The standard deviation of the mPA of LV blood pool (SD LVmPA) represents synchronicity of ventricular motion. SD LVmPA can be expressed in units of degree/angle (°) or time, that is, milliseconds (ms). Expressing SD of mPA in degrees is considered more accurate for comparison across different populations since it negates the effect of different heart rates (and thus R–R interval) among individuals. However, both units are analogous to each other and either can be used for statistical analysis within a sample.{Figure 1}

To define intra-LV mechanical dyssynchrony (ILVD), we used cutoff values (mean + 2SD of SD LVmPA) of ERNA which are already established in normal Indian controls.[22] ILVD was thus diagnosed when SD LVmPA value was >13.2° (or >27.1 ms), in the study population.[22] Apart from quantitative analysis, qualitative visual assessment of the phase images was also done to determine LV regional dyssynchrony.

Speckle-tracking echocardiography acquisition and processing

Echocardiography was performed by an experienced cardiologist in the left lateral decubitus position using the commercially available equipment (Philips Inc.). Data acquisition was performed with a 3-MHz transducer at a depth of 15 cm in the parasternal and apical views (standard 2- and 4-chamber images). For speckle-tracking analysis, standard grayscale two-dimensional (2D) images were acquired in the parasternal short-axis views at the level of the papillary muscles. All of the images were recorded with a frame rate of at least 50 fps to allow for reliable operation of the software (QLab; Koninklijke Philips N.V.). Sector width was also adjusted to ensure that the whole of the LV wall was included in the acquisition, while at the same time, recording as narrow a sector as possible to optimize temporal resolution.

Offline analysis was done on all the recordings, using the vendor provided customized software package (QLab; Koninklijke Philips N.V.). From an end-systolic single frame, ROI were traced on the endocardial cavity interface by a point-and-click approach. Then, an automated tracking algorithm followed the endocardium from this single frame throughout the cardiac cycle. Further, adjustment of the ROI was performed to ensure that all of the myocardial regions were included. Next, acoustic markers, the so-called speckles, equally distributed in the ROI, were followed throughout the entire cardiac cycle. The distance between the speckles was measured as a function of time, and parameters of myocardial deformation were calculated. Circumferential strain (CS) was calculated by dividing the myocardium into six segments, namely, the mid-anterior, mid-anterolateral, mid-inferolateral, mid-inferior, mid-inferoseptal, and mid-anteroseptal. The different segments were color coded, and CS curves were reconstituted in each of the six mid-LV segments [Figure 2].{Figure 2}

Parameters derived from speckle-tracking echocardiography

Using peak of the R wave as a reference, time to attain the peak systolic CS was calculated for each segment. To identify dyssynchrony, the “dyssynchrony index” of the LV was calculated as the standard deviation of time-to-peak systolic CS (SDCS) of the six segments.

To calculate the upper limit of the normal value of SDCS, STE was preperformed on 10 apparently healthy volunteers with no history of cardiovascular symptoms and normal ECG and routine echocardiographic parameters. The cutoff limit (mean + 2SD) thus derived to define ILVD from STE was SDCS >74 ms.

Each of the 55 patients first underwent routine 2D echocardiographic examination. However, 2D speckle-tracking acquisition was only possible in 42 patients, in whom satisfactory and low-noise LV short-axis images could be obtained in the parasternal view.

Statistical analyses

Data are presented as mean with standard deviations or median with ranges where appropriate. The Chi-square test/Fisher's exact test was used for the comparison of categorical (qualitative) data between groups. For continuous variables, the Student's t-test/Mann–Whitney U-test was applied for comparison between the means of two groups. Kappa analysis and McNemar's test were used to assess intermodality agreement. Pearson's “r”/Spearman's ρ was used to assess the correlation between quantitative variables where appropriate. Agreement between representative quantitative measures of the two imaging modalities was further tested by calculating Cohen's kappa value and Bland–Altman analysis. P < 0.05 was considered statistically significant. All the data analyses were performed using the statistical software packages SPSS 17 (SPSS Inc., Chicago, Illinois, USA) and MedCalc 11.3 (MedCalc Software, Mariakerke, Belgium).


The baseline characteristics of the original sample of 55 patients who underwent ERNA and those of the subset of 42 patients in whom STE acquisition could be done for the comparison are summarized in [Table 1]. The subset of 42 patients (26 males and 16 females) had a mean age of 41.2 ± 10.5 years (range: 19–59 years). The mean LVEF for the entire sample (n = 55) was 28% ± 8% (range: 15%–40%) and that of the subset (n = 42) was 26% ± 7.7% (range: 15%–40%). The clinical characteristics of this subset (n = 42) were compared with the remaining 13 patients in whom STE could not be performed, and no significant differences were observed in age and sex distribution, etiology of DCM, New York Heart Association class, and presence of left bundle branch block (LBBB) (P > 0.05 for all comparisons). However, QRS duration was significantly shorter (P = 0.01) and LVEF relatively better (P = 0.02) in patients in whom STE could not be performed.{Table 1}

Intermodality agreement

Since the reference upper limits to label dyssynchrony for both modalities, that is, STE and ERNA were derived from two separate control groups, their demographic profile was compared to the respective patient populations. No significant difference was found in age distributions between patients and STE controls (41.2 ± 10.5 vs. 41 ± 9 years, P = 0.595) or patients and ERNA controls (42.5 ± 11 vs. 46.2 ± 14.5 years, P = 0.109).

Using the above-described cutoffs, out of 42 patients, ILVD was found in 27 (64%) patients on speckle-tracking analysis and 31 (74%) patients on ERNA. ERNA identified LV mechanical dyssynchrony in all 27 patients classified as having dyssynchronous contraction on STE. The former additionally detected dyssynchrony in four patients in whom results of STE were normal. McNemar's analysis revealed no statistically significant difference between the mechanical dyssynchrony detection by STE and ERNA (P = 0.125) [Table 2] and [Figure 3], and [Figure 4]. The results from the two modalities were further tested by Cohen's Kappa test for intermodality agreement. Kappa value of 0.780 was derived (P < 0.0001), which indicated good agreement.{Table 2}{Figure 3}{Figure 4}

A Shapiro–Wilk test showed that the quantitative parameters of dyssynchrony derived from ERNA (i.e., SD LVmPA) and STE (i.e., SDCS) were not normally distributed in the sample (test statistic 0.91; P < 0.05 and test statistic 0.94; P < 0.05, respectively). The association between the two parameters was therefore tested by Spearman's rank correlation test. On analysis, the Spearman's rho (ρ) value was derived to be 0.690 (P < 0.0001), indicating a moderately strong linear correlation [Figure 5]. Bland–Altman plot was also constructed to further test the agreement between the above parameters, and the results are summarized in [Figure 6]. The analysis revealed that differences between almost all the paired measurements were contained within two standard deviations of difference, indicating acceptable agreement. Furthermore, a trend was observed that as the absolute magnitude of dyssynchrony increases, the difference between STE and ERNA measurements increases, indicating that in highly dyssynchronous LV contractions, either ERNA underestimates or STE overestimates the dyssynchrony. The validation and explanation of this later finding however require further research in future studies with larger sample sizes.{Figure 5}{Figure 6}

Electrocardiogram versus imaging for mechanical dyssynchrony

Among the study population (n = 55), 21 patients (38%) had wide QRS (duration >120 ms). Eleven out of these (20% of total) had LBBB, and two had right bundle branch block pattern. The remaining eight patients (14% of total) were classified as having nonspecific intraventricular conduction defects. In patients with wide QRS, the mean QRS duration was 148 ± 18 ms (range: 122–189 ms). The relationship of electrical with mechanical dyssynchrony was compared between wide QRS and narrow QRS group using both ERNA (n = 55) and STE (n = 42). While assessed by ERNA, 5 out of 21 patients (20%) with wide QRS duration on ECG did not show mechanical intra-LV dyssynchrony. On the other hand, 21 out of 34 patients (62%) with otherwise narrow QRS showed intra-LV mechanical dyssynchrony. The Chi-square test did not show a significant association of QRS duration and ILVD (P = 0.268). When assessed with STE, again no significant association of QRS duration was noted with ILVD (P = 0.167).

Effect of LBBB on mechanical dyssynchrony was also assessed using ERNA and STE. Nine out of 11 (82%) patients with LBBB showed ILVD on ERNA; however, 28 out of 44 (64%) patients without LBBB also showed ILVD. Overall, no significant association was found between the presence or absence of LBBB and ILVD (P = 0.429; Chi-square test with continuity correction). Similar results are found with STE (P = 0.117; Chi-square test with continuity correction).

We also found that patients with ILVD on ERNA had lower LVEF (24.3% ±6%; median 23%, range 15%–36%) compared to patients without ILVD (34.2% ± 7%; median 37.5%, range 16%–40%) and the difference was statistically significant (P < 0.001). A moderately negative Spearman's correlation (ρ = −0.672) was observed between SD LVmPA and LVEF (P < 0.01) [Figure 7].{Figure 7}


ERNA is a well-established modality for evaluating both global and regional cardiac functions. It is accurate, reproducible, and simple to perform. Various studies have assessed the feasibility of ERNA in assessing mechanical synchrony and have also validated the accuracy of the method.[19],[20],[21],[22] However, to make this technique proceed from the bench to the bedside, we compared and correlated ERNA with the modality, the cardiologist is most familiar with, that is, the echocardiography. To the best of our knowledge, this is the first study comparing ERNA and STE for the assessment of LV mechanical dyssynchrony.

Out of 55 patients with normal sinus rhythm in whom ERNA was successfully performed, adequate parasternal view echocardiographic recording for offline speckle-tracking analysis was possible in only 42 (76%) patients. This was attributed to poor acoustic window in the remaining patients owing to thick chest wall (obesity), rib crowding artifacts, obstructive airway disease, etc., Offline speckle tracking on the images of these patients was visually found to be inconsistent, with poor reproducibility. This is consistent with several previous studies that have reported that lack of adequate imaging window is a limitation of echocardiography in general, even more relevant when performing STE which requires images with high spatial resolution.[23],[24],[25] In comparison, image degradation due to overlying soft-tissue attenuation is unlikely during ERNA acquisition. In a subgroup analysis, we found that among the clinical characteristics, QRS duration was significantly shorter and LVEF relatively better in patients in whom STE could not be performed. This may occur because patients with coexisting obesity or obstructive airway disease are more likely to be symptomatic and seek consultation in heart failure clinic at earlier stages with relatively preserved cardiac function. ILVD was thus serially assessed by both modalities in the subsample of 42 patients and the agreement analysis for the detection of mechanical dyssynchrony showed strong agreement between the two modalities.

Compared to STE, ERNA identified ILVD in four additional patients. Visual analysis of the phase images of these patients revealed that the region of dyssynchrony was confined to the apical/inferoapical region. The significance of this finding remains uncertain but may reflect the inherent limitation of 2D nature of speckle tracking which may not provide coverage of adequate longitudinal length of the LV, while dyssynchrony in itself is a 3D phenomenon.[26],[27] 3D speckle-tracking technology can overcome the limitations of 2D sampling.[27]

In this study, the QRS duration and LBBB status were not found to have strong correlation with ILVD. Literature review shows conflicting data on the exact relationship of QRS duration with ILVD. Fauchier et al.[16] reported higher values of SD LVmPA in DCM patients with QRS >120 ms, while Marcassa et al.[28] reported only a weak correlation between QRS duration and SD LVmPA (r = 0.51). However, in the studies by Ghio et al.[29] and Hara et al.,[30] no significant relation was found between ILVD and wide QRS. Our study supports the later studies. Although 76% of our patients with wide QRS had ILVD, 62% of patients with narrow QRS also have ILVD. Other authors have reported the presence of ILVD in up to 50% of patients with normal QRS duration.[28],[31]

Interestingly, not all patients with wide QRS show ILVD. Previous studies [28],[29],[30] have reported that up to 42% of patients with wide QRS may not have ILVD. In this study, 24% of the patients did not show ILVD despite having QRS width >120 ms. This percentage is very similar to the proportion of nonresponders in the various CRT trials, giving impetus to the hypothesis that the presence of ILVD may be a necessary factor behind the response to CRT.

Ventricular synchrony and function are closely related. Dyssynchronous contraction may have a significant detrimental effect on mechanical pumping efficiency of the ventricles. This is reflected as reduced global ventricular systolic function. Studies by several workers in the past have supported this theory. Fauchier et al.[16] reported in 103 patients with idiopathic DCM that a degradation of the hemodynamic status was associated with an increase in ILVD. Among 13 univariate predictors of cardiac events, the only independent predictors were an increased SD LVmPA (P = 0.0004) and an increased pulmonary capillary wedge pressure (P = 0.009). Marcassa et al.[28] reported in 130 DCM patients, a significant nonlinear inverse relation of LVEF with ILVD (r = −0.68, P < 0.0001) concordant with our study.

CRT, by means of correcting dyssynchrony, may help in the improvement of LVEF which may be linked with the overall clinical response. It is pertinent thus to investigate the parameter of ventricular synchrony which has the greatest impact on ventricular function measured as LVEF.

The above findings suggest that ILVD might be more important than QRS duration in determining LV function and the subsequent prognosis and should, therefore, be the target of resynchronization therapy. The fact that ERNA has high accuracy and reproducibility in the assessment of ILVD underlines its potential applicability in the assessment of patients with heart failure who are potential candidates for resynchronization therapy.


ERNA as a modality for the assessment of cardiac mechanical dyssynchrony compares favorably with the current standard of care echocardiographic technique for this purpose, that is, STE. The former also overcomes the inherent limitations of the latter in being operator independent and thus being more reproducible and also in being applicable to a wider subset of patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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