Noninvasive detection of myocardial ischemia in patients with left bundle branch block (LBBB) remains a challenge [1, 2]. The condition is often associated with coronary artery disease or hypertension, but frequently there is no indication of cardiovascular disease. Exercise-induced electrocardiographic ST-segment changes are non-diagnostic. Myocardial perfusion scintigraphy has been widely used in LBBB patients whereby anteroseptal defects have been observed in the absence of significant left anterior descending (LAD) coronary artery disease [3–5]. Several mechanisms have been proposed to explain this false-positive phenomenon such as metabolic alterations, cardiomyopathic changes, altered relaxation due to abnormal conduction, changes in septal wall motion, reduced septal wall thickening, and redistribution of coronary perfusion [6–10]. Generally, irreversible perfusion defects in the anteroseptal wall and apex are caused by a constant, stress-independent mechanism, whereas reversible defects may indicate underlying ischemia induced by a significant LAD stenosis. The major challenge in LBBB patients remains, however, to discriminate between artifactual septal defects and true ischemic defects. Various interpretative methods and stress techniques have been evaluated in an attempt to improve the specificity of noninvasive studies for detecting LAD disease in LBBB patients [11]. The application of pharmacologic stress has resulted in higher specificity than conventional exercise scintigraphy because of a more uniform exploitation of coronary flow reserve [12]. Recently gated myocardial SPECT imaging has been applied to elicit the underlying mechanisms of perfusion abnormalities in patients with LBBB [13–16]. Bavelaar-Croon et al. [14] studied 37 LBBB patients without a history of a previous myocardial infarction who underwent technetium-99 m tetrofosmin gated SPECT imaging. There was no correlation between perfusion and function in the septum, but a good correlation between perfusion and function in the remote segments, implying that patients with LBBB without a previous myocardial infarction show cardiomyopathic changes with perfusion and wall motion abnormalities involving the entire left ventricle. Several studies have emphasized the relevance of gated SPECT in LBBB patients by evaluating the enddiastolic images [17–19]. Inanir et al. [17] evaluated the diagnostic role of dipyridamole Tc-99 m sestamibi gated SPECT in 20 patients with LBBB without known coronary artery disease. Angiographic findings correlated best with those of end-diastolic images, indicating that end-diastolic images can significantly reduce artifactual defects in patients with LBBB. Demir et al. [18] showed that gated SPECT imaging, in particular the end-diastolic images, revealed fewer false positive results in patients with LBBB. Also Afzal et al. [19] showed that patients with LBBB reduced septal thickening resulted in artifactual septal perfusion defects. Consequently, gating the perfusion scintigraphy and reporting perfusion status on end-diastolic frames in LBBB patients may eliminate artifacts in the septal wall.

In the current issue of the International Journal of Cardiovascular Imaging, Nichols et al. [20] tried to assess which asynchrony parameter derived from gated SPECT systolic wall thickening data best distinguishes LBBB patients from normal subjects. Emory Cardiac Toolbox algorithms were used to compute left ventricular global and regional function and perfusion indices with regional contraction phases for 20 patients with LBBB, and in nine control subjects. Z-score asynchrony measures were derived for phases sampled using the conventional 17-segment model. Z-scores are dimensionless parameters computed as the difference between phase standard deviation minus mean phase standard deviation for a normal population. In the normal subjects contraction occurred nearly simultaneously in all segments, while LBBB patients showed a wide variety of heterogeneous contraction patterns. Z-scores most strongly discriminated LBBB patients from control patients (93% correctly predicted).

Evaluation of asynchrony/dyssynchrony parameters is clinically a very relevant issue in LBBB patients who are being considered for cardiac resynchronization therapy (CRT). Many studies have already observed left ventricular dyssynchrony in LBBB patients with heart failure for whom CRT with biventricular pacing has been shown to be beneficial, particularly when left ventricular ejection fraction (LVEF) is <35% and QRS duration >120 ms [21–26]. However, 20–30% of patients with congestive heart failure and LBBB who meet criteria for CRT do not derive significant clinical benefit from the procedure. Novel parameters have been sought to predict clinical responsiveness to CRT that are superior to the purely electrocardiographic and LVEF criteria. Although gated SPECT imaging has been widely used to evaluate myocardial perfusion and cardiac function in patients with heart failure, recently more advanced gated SPECT data processing techniques including phase analysis have been employed to evaluate left ventricular synchronicity [27–33]. Henneman et al. [32] studied 75 patients with heart failure, depressed left ventricular function, and wide QRS complex using gated SPECT and two-dimensional echocardiography, including tissue Doppler imaging (TDI). It was shown that left ventricular dyssynchrony assessed from gated SPECT correlated well with dyssynchrony assessed by TDI. The histogram bandwidth and phase standard deviation showed the best correlation with left ventricular dyssynchrony on TDI. The results of this study [32] support the use of phase analysis by gated SPECT to evaluate left ventricular dyssynchrony. Trimble et al. [33] used phase analysis of gated SPECT to examine the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in 125 patients with left ventricular dysfunction. It was shown that heart failure patients with perfusion abnormalities or prolonged QRS durations have higher degrees of mechanical dyssynchrony.

To summarize, gated SPECT myocardial imaging can quantify myocardial function, perfusion, and left ventricular dyssynchrony and may help in evaluating LBBB patients for CRT. The study of Nicols et al. [20] adds a new dimension to the already existing dyssynchrony parameters allowing the identification of patients who qualify for CRT.