Phase Analysis: A New Armamentarium in Nuclear Cardiology

Phase analysis tool has evolved significantly since its inception in 2005 by Chen et al.[1] It has added another dimension to cardiac assessment using radionuclide techniques for the detection of left ventricular mechanical dyssynchrony (LVMD). LVMD refers to asynchronous mechanical contraction and/or relaxation between different segments of the left ventricle. It is important to acknowledge that mechanical dyssynchrony does not equal electrical dyssynchrony which is defined by an asynchronous electrical activation of the left ventricular (LV) leading to a prolonged QRS duration (>120 ms) on the electrocardiogram.[2] Prolonged QRS duration is one of the significant constituents of traditional criteria for the selection of cardiac resynchronization therapy (CRT) candidates; other components include LV ejection fraction ≤35% and New York Heart Association class II-IV despite optimal medical therapy. Based on the current traditional criteria, ~20%–30% of patients fail to show an improvement in clinical symptoms and cardiac function after CRT, suggesting the need for a more efficient selection of CRT candidates to improve patient outcomes.[3] Phase analysis might come to the rescue of these patients as the assessment of LVMD has shown to aid in selecting the CRT candidates. LMVD has been studied using several imaging modalities including echocardiography (M-mode, color tissue Doppler, strain imaging, and three-dimensional echo), cardiac magnetic resonance imaging, and cardiac radionuclide techniques including myocardial perfusion imaging (MPI) single-photon emission tomography (SPECT) and positron emission tomography and gated blood pool imaging.[14] Dyssynchrony analysis using radionuclide techniques has several advantages over other modalities including the use of automated technology, ease of standardization to ensure reliability and reproducibility, and lack of limitations such as requiring proper acoustic window which has been adequately highlighted in the present study published in the current issue by Singhal et al.[5]

The author has compared the utility of equilibrium radionuclide angiography (ERNA) with the speckle tracking echocardiography (STE) in the diagnosis of LVMD in a subset of 55 patients with dilated cardiomyopathy. STE could not be performed in thirteen patients (24%), which was attributed to poor acoustic window owing to the thick chest wall (obesity), rib crowding artifacts, and obstructive airway disease. Offline speckle tracking on the images of these patients was visually found to be inconsistent, with poor reproducibility, highlighting significant limitations of STE despite its wider availability and applicability. Furthermore, the author could detect the LVMD in greater number of patients (31 vs. 27 respectively) on ERNA as compared to the STE. These findings highlight the utility of ERNA in the detection of LVMD in greater number of patients and subsequent better management which can be easily missed on the STE due to various reasons. Among the study population, the author also compared the relationship of electrical versus mechanical dyssynchrony between wide QRS and narrow QRS group using both ERNA and STE techniques, and no significant association of QRS duration was noted with LVMD. Furthermore, the presence of LBBB does not alter LVMD status suggestive of its independent existence from electrical dyssynchrony, as all patients with wide QRS do not show LVMD. The present study shows that 24% of the patients did not show LVMD 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 LVMD may be a necessary factor behind the response to CRT.

Studies in patients with ischemic and nonischemic cardiomyopathy have shown that LVMD is associated with a higher risk of mortality and portends a poor prognosis. LV mechanical dyssynchrony even in the absence of perfusion or function abnormalities has shown to predict adverse cardiovascular outcomes in women, in patients with diabetes mellitus and patients with end-stage renal disease.[4678] Being noninvasive, operator independent, highly reproducible, and relatively easy to perform, phase analysis seems to be one of the most promising techniques to quantify left ventricle dyssynchrony in comparison to the conventionally available techniques. Its ability to apply on retrospective data provides further advantage, and it can be expressed in units of degree/angle (°) or time, i.e., milliseconds depending upon cardiologist preference. Limited availability of gamma camera and nonstandardization of the dyssynchrony parameters restricts its use as the investigation of choice for diagnoses of LVMD.

Besides these drawbacks, we should consider incorporating dyssynchrony analysis in the routine interpretation of cardiac radionuclide techniques (SPECT-MPI and ERNA) along with other parameters whenever possible. However, this would require a standardization of the dyssynchrony parameters and a seamless incorporation of analysis algorithm in the programs used for interpretation in routine clinical practice. Although phase analysis is known for a long time, this modality is grossly underutilized for the evaluation of cardiac dyssynchrony. Heart failure patients, who despite optimal medical therapy continue to be symptomatic, should be selected for CRT if significant cardiac mechanical dyssynchrony is detected on phase analysis, for a better result.