Prognostic value of left ventricular mechanical dyssynchrony by phase analysis in patients with non-ischemic cardiomyopathy with ejection fraction 35-50% and QRS &lt; 150 ms

Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) remains one of the most commonly ordered tests for the detection of ischemia and significant coronary artery disease (CAD). 1 A coronary artery territory perfused by a significantly narrowed vessel has limited coronary flow reserve; hence, during peak stress, there are less blood flow and tracer uptake in that region as compared to normal myocardial. The detection of reversible perfusion defect, therefore, depends on the relative flow between myocardial territories. 2 In patients with multivessel disease, the coronary flow reserve is reduced in all territories leading to what has been described as balanced ischemia phenomenon. 3 The latter poses a challenge as patients with multi-vessel CAD may have ''normal'' MPI and could be miss-diagnosed or more commonly assumed to have less extensive CAD. 3 However, other complementary tools have helped recognize the presence of high ischemic burden even when the perfusion images say otherwise. Among them, transient ischemic dilation (TID), 4 increased lung uptake of 5 and left ventricular (LV) stunning (i.e., decrease in early post-stress LV ejection fraction [EF]). These tools, nevertheless, have limitations: the diagnostic accuracy of TID is low; Tl-201 is rarely used and has been replaced by Tc-99m; and LV stunning is often missed or underestimated since imaging with SPECT does not occur at peak stress giving enough time for LV recovery. 6 LV mechanical dyssynchrony indices have been proposed as additional tools to help detect myocardial stunning and ischemia-induced dyssynchronous contraction. The technique was developed by Chen 7 almost a decade ago. It calculates a phase value for each of sampled regions ([600) that represent the onset of mechanical contraction. The standard deviation (phase SD) and 95% bandwidth (histogram bandwidth) represent the LV dyssynchrony indices: the bigger the numbers, the greater the dyssychrony. These indices are derived retrospectively from prior acquired and saved images, with no additional radiation burden or cost. They are automated, reproducible with small inter and intra-observer variability, 8 repeatable, 9 and have been validated against two 10 and three-dimensional echocardiography. 11 The initial application of the technique was in identifying the optimal patients with cardiomyopathy who would derive most benefit from cardiac resynchronization therapy. 12 Since then, the technique proved not only to be a valuable tool in detecting mechanical dyssynchrony, but also providing prognostic information and risk stratifying patients with various co-morbidities (ischemic, 13 non-ischemic cardiomyopathy, 14 implantable defibrillators, 15 end-stage renal disease 16,17 ). More recently, the technique has been used to detect ischemiainduced myocardial dyssynchrony and multi-vessel CAD by comparing stress and rest indices [18][19][20] (Table 1).The concept of stress-induced changes in LV dyssynchrony is not new. In patients with normal MPI undergoing gated...

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confidence: 99%

Early post-stress LV dyssynchrony: A new marker for significant CAD

AlJaroudi

2014

“…It was shown to predict ICD shock, 14 and all-cause mortality. 15,16 In addition, it was tested and validated with PET imaging. 17 However, phase analysis faced several challenges…”

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confidence: 99%

“…It was shown to predict ICD shock, 14 and all-cause mortality. 15,16 In addition, it was tested and validated with PET imaging. 17 However, phase analysis faced several challenges including; (1) different vendors have different software and values without any way to standardize; (2) limited temporal resolution despite complex mathematical way to bypass it; (3) noise and artifact from areas with significantly reduced perfusion due to scar; (4) SPECT myocardial perfusion imaging is not performed routinely prior to CRT unlike echocardiography; and (5) limited data post-CRT placement as it requires repeat testing and tracer injection.…”

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confidence: 99%

Mechanical dyssynchrony with phase analysis of gated SPECT: Nap time is over

AlJaroudi

2018

Cardiac resynchronization therapy (CRT) improves left ventricular (LV) remodeling, quality of life, and survival among patients with heart failure and reduced ejection fraction (EF \ 35%) and electrical dyssynchrony (wide QRS duration). [1][2][3] However, a significant proportion of patients do not derive the expected benefit from such expensive and invasive procedure. 4 In 2011, Goldengerb et al. identified 7 factors from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial that improved patient selection and predicted better CRT response; 5 these included female gender, non-ischemic cardiomyopathy, left bundle branch block (LBBB), QRS C 150 ms, prior hospitalization for heart failure, left ventricular end-diastolic volume index C 125 ml/m 2 , and left atrial volume index less than 40 ml/m 2 . Shortly after, the 2012 guidelines for CRT implantation were updated and recommended CRT for patients with EF B 35%, NYHA class C II with LBBB, and QRS C 150 ms (the only class I indication) as compared to a QRS threshold C 120-130 ms with 2008 guidelines. 6 The more stringent QRS threshold for CRT implementation was meant to choose patients with greater electrical dyssynchrony, thus greater mechanical dyssynchrony, and therefore those with higher chance of CRT restoring synchronicity of myocardial contraction. However, electrical and mechanical dyssynchrony are not interchangeable, 7,8 which explains in part the remaining high rate of non-responders. 9 Because of its non-invasiveness, low cost, and wide availability, significant effort and research were placed on identifying mechanical dyssynchrony parameters with echocardiography that would be best predictive of CRT response. Indeed, an exponential increase in the number of research papers was observed in the field of echocardiography between 2004 and 2008 exploring dozen of parameters with 2D, 3D echocardiography, strain, strain rate, and many others (Fig. 1). Promising single-center data were published, while others had conflicting data, until the negative and conclusive results of PROSPECT trial, a multicenter study that tested many echocardiography parameters (interobserver and intraobserver variability 4%-24% and 7%-72%, respectively) all of which failed to predict CRT response. 10 Shortly thereafter, interest in mechanical dyssynchrony with echocardiography took a significant hit, and despite recent efforts to revive it, 11 the number of publications kept on declining dramatically (Fig. 1).In 2005, Chen et al. published one of the first papers on mechanical dyssynchrony using phase analysis concept from gated single-photon emission computed tomography (SPECT). 12 Briefly, a 3D count distribution is extracted from each of the LV short-axis datasets; 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. 12 Unlike echocardiography, SPECT myocardial...

“…8 It was found that PSD and PBW were associated with a significantly higher incidence of MACE (P \ 0.001) and proved to a strong predictor of MACE independent of other known predictors such as perfusion defects or decreased leftventricular ejection fraction (LVEF). Goldberg et al 9 enrolled 324 consecutive patients with non-ischemic cardiomyopathy (NICM), LVEF 35%-50%, and QRS \ 150 ms and found that the patients who died had a trend toward a higher mean PSD (P = 0.1) and PBW (P = 0.08). After adjusting for age, hypertension, diabetes, aspirin, beta-blockers, diuretics, QRS, and LVEF, PSD and PBW were independent predictors of all-cause mortality and added incremental prognostic value (P = 0.025 for PSD).…”

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confidence: 99%

Left-ventricular mechanical dyssynchrony in the prognosis of dilated cardiomyopathy: Which parameter is more useful?

Zhou

Hung

2018

Since the invention of the phase analysis technique from ECG-gated myocardial perfusion SPECT by Chen et al in 2005,1 it has been widely used to measure leftventricular mechanical dyssynchrony (LVMD). Briefly, the phase analysis technique applies a one-dimensional First-harmonic Fourier approximation to the count variation over cardiac frames for each myocardial region on nuclear images and thus generates a 3D phase distribution that describes the timing of LV onset of mechanical contraction over the entire R-R cycle.1,2 The technique is fully automated, and has effective temporal resolution of *15 ms for a heart rate of 60/minute, high inter-and intra-observer reproducibility, good robustness with camera types, tracer dose, heart rate, and perfusion defects. 2,3The commonly used clinical parameters from phase analysis include peak phase (PP), phase standard deviation (PSD), phase bandwidth (PBW), phase histogram skewness, and phase histogram kurtosis. The normal databases consisted of PP (134.5°± 14.3°for men and 140.2°± 14.9°for women), PSD (14.2°± 5.1°for men and 11.8°± 5.2°for women), PBW (38.7°± 11.8°for men and 30.6°± 9.6°for women), skewness (4.19 ± 0.68 for men and 4.60 ± 0.72 for women), and kurtosis (19.72 ± 7.68 for men and 23.21 ± 8.16 for women).1 The LVMD parameters have been shown to correlate well with those by tissue Doppler imaging (TDI) echocardiography. 4,5 Henneman et al 4 found that PSD and PWB by phase analysis from SPECT correlated well with LVMD assessed with 2D TDI (r = 0.80, P \ 0.0001 and r = 0.89, P \ 0.0001, respectively); histogram skewness and kurtosis correlated less well with LVMD on 2D TDI (r = -0.52, P \ 0.0001 and r = -0.45, P \ 0.0001, respectively). Marsan et al 5 found that PSD and PBW showed good correlation with 3D TDI (r = 0.74, P \ 0.0001 and r = 0.77, P \ 0.0001, respectively); histogram skewness showed a poor correlation with 3D TDI (r = -0.30, P = 0.06); there was no correlation between histogram kurtosis and 3D TDI (r = -0.14, P = 0.38). PSD and PBW showed the best correlation with the dyssynchrony assessed with echo; hence, they are more commonly used to report the LVMD from gated myocardial perfusion SPECT.Furthermore, PSD and PBW have been extensively used for the patient selection and prognosis of cardiovascular diseases. In a study with 42 cardiac resynchronization therapy (CRT) patients, 6 it was demonstrated that responders (71%) and non-responders (29%) had comparable baseline characteristics, except for PSD (56.3°± 19.9°vs. 37.1°± 14.4°, P \ 0.01) and PBW (175°± 63°vs. 117°± 51°, P \ 0.01), which were significantly larger in responders compared with non-responders. Moreover, the receiver operating characteristic (ROC) curve analysis demonstrated an optimal cutoff value of 43°for PSD (sensitivity and specificity of 74%) and of 135°for PBW (sensitivity and specificity of 70%) for the prediction of CRT response. In a study with 22 patients who had irreversible ischemic cardiomyopathy and received CRT for at least 12 months, 7 it was found that PBW was an inde...