Assessment of left ventricular mechanical dyssynchrony by phase analysis of ECG-gated SPECT myocardial perfusion imaging

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset–of–mechanical contraction phase. Once the onset–of–mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.

Introduction

As the diagnosis and treatment of coronary artery disease (CAD) have continued to progress in recent years, more and more patients die of heart failure (HF). HF affects more than 5 million persons in the United States. Approximately 550,000 new cases are diagnosed annually, and acute decompensated HF accounts for more than 1 million hospital admissions per year.¹ The estimated direct and indirect cost for HF in 2006 was $29.6 billion.²

Cardiac resynchronization therapy (CRT) can benefit some patients with end-stage HF, depressed left ventricular ejection fraction (LVEF) (<35%), and a wide QRS complex on the surface electrocardiogram (>120 milliseconds)³; however, these selection criteria are suboptimal, given that in previous CRT trials using these criteria, a significant percentage of patients (20%-40%) did not benefit from CRT.3, 4, 5, 6 It has been recognized that electrical dyssynchrony as determined by QRS duration may not necessarily represent mechanical dyssynchrony and, therefore, may not represent the best predictor of response to CRT.7, 8, 9 Therefore assessment of cardiac mechanical dyssynchrony is needed to more accurately select patients who would more consistently benefit from CRT. Recent data have indicated that left ventricular (LV) mechanical dyssynchrony may be mandatory for prediction of CRT responses.10, 11

Assessment of LV dyssynchrony has been approached with a number of imaging techniques, such as echocardiography with tissue Doppler imaging (TDI) or strain imaging,12, 13, 14 magnetic resonance imaging,15, 16 gated blood pool ventriculography, and single photon emission computed tomography (SPECT).17, 18, 19 Recently, phase analysis has been developed for assessment of LV dyssynchrony from gated SPECT (GSPECT) myocardial perfusion imaging (MPI).²⁰ This technique can have a significant impact clinically because it allows GSPECT MPI, the most widely used nuclear imaging procedure for the management of CAD, to assess cardiac dyssynchrony and HF. It has been noted that the most common cause of chronic HF is no longer hypertension or valvular heart disease, but rather CAD.²¹ In 13 multicenter HF treatment trials reported in the New England Journal of Medicine,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 involving more than 20,000 patients, CAD was the underlying etiology of HF in nearly 70% of patients. The importance of CAD is underscored by the observation that the prognosis of patients with HF and CAD is considerably worse than that of patients without CAD and is related to the angiographic severity of CAD.³⁵ GSPECT MPI has an important role in the diagnosis and management of patients with LV dysfunction. Potential benefits for its use in the evaluation of LV dyssynchrony include its widespread availability, automation, and reproducibility. Additional prognostic information can be obtained from 3-dimensional (3D) perfusion images including the presence and location of myocardial scar tissue. This has recently been shown to adversely affect response to CRT.³⁶ One potential advantage is that the location, extent, and severity of scar could be identified from the same perfusion images. This knowledge may impact site selection for LV pacing lead placement.

In this article the phase analysis methodology is reviewed. Validations of this technique versus other imaging techniques in measuring LV dyssynchrony and versus clinical outcomes are also summarized.