Incremental value of myocardial wall motion and thickening to perfusion alone by gated SPECT myocardial perfusion imaging for viability assessment in patients with ischemic heart failure

Abstract

Purpose.

The objective of this study was to assess the incremental value of myocardial wall motion and thickening compared with perfusion alone obtained from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in diagnosing myocardial viability in patients with ischemic heart failure.

Methods.

Eighty-three consecutive patients with ischemic heart failure who underwent both ^99mTc-MIBI gated SPECT MPI and ¹⁸F-FDG positron emission tomography (PET) myocardial metabolic imaging were retrospectively enrolled. SPECT/PET myocardial viability was defined as the reference standard. Segmental myocardial perfusion, wall motion, and thickening were measured by an automated algorithm from gated SPECT MPI. Univariate and stepwise multivariate analysis were conducted to establish an optimal multivariate model for predicting hibernating myocardium and scar.

Results.

Among the 1411 segments evaluated, 774 segments had normal perfusion and 637 segments had decreased perfusion. The latter were classified by ¹⁸F-FDG PET into 338 hibernating segments and 299 scarred segments. The multivariate regression analysis showed that the model that combined myocardial perfusion uptake with wall motion and thickening scores had the optimal predictive efficiency to distinguish hibernating myocardium from scar in the segments with decreased perfusion. The model had the largest C-statistic (0.753 vs 0.666, P < 0.0001), and the global chi-square was increased from 53.281 to 111.234 when compared with perfusion alone (P < 0.001).

Conclusions.

Assessment of myocardial wall motion and thickening in addition to conventional perfusion uptake in the segments with decreased perfusion enables better differentiation of hibernating myocardium from scar in patients with ischemic heart failure. Considering wide availability and high cost-effectiveness, regional myocardial function integrated with perfusion on gated SPECT MPI has great promise to become a clinical tool in the assessment of myocardial viability.

INTRODUCTION

The assessment of myocardial viability has a vital role in the management of patients with ischemic heart failure.¹ The detection of viable but dysfunctional (hibernating) myocardium has been widely used to predict recovery of contractile function after revascularization.^2,3 Of various noninvasive imaging techniques for discriminating hibernating myocardium and scar, ¹⁸F-deoxyglucose (FDG) positron emission tomography (PET) is currently considered as the most sensitive approach.^4,5 However, the medical cost necessary to perform PET is expensive and the equipment is not extensively available, which greatly limits its wide use in clinical practice.^6,7

Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established and widely available noninvasive imaging technique that can not only measure myocardial perfusion, but also obtain a variety of quantitative indicators such as global left ventricular (LV) function, volume, as well as regional myocardial function (wall motion and thickening) through one-step inspection with high reproducibility and repeatability.^8,9 Previous studies have confirmed that segments with ≥ 50% perfusion uptake can accurately identify viable myocardium.^10,11 However, the abnormally contracting segments with perfusion uptake < 50% also contain a substantial amount of hibernating myocardium in patients with coronary artery disease (CAD), leading to an underestimate of viable myocardium.^12,13 Furthermore, regional myocardial function analysis by gated SPECT MPI provides additional information compared with perfusion for the prediction of segmental functional recovery after revascularization in patients with previous myocardial infarction (MI).¹⁴ The method using gated SPECT MPI to identify hibernating myocardium in hypoperfused segments has not been thoroughly established. Therefore, we hypothesized that gated SPECT MPI alone may determine myocardial viability by an integral assessment of myocardial function and perfusion. The objective of this study was to evaluate the incremental value of myocardial wall motion and thickening of each segment calculated by gated SPECT MPI to perfusion alone for distinguishing hibernating myocardium from scar in patients with ischemic heart failure.

METHODS

Study Population

We retrospectively studied 83 consecutive patients who had undergone both rest gated SPECT MPI and ¹⁸F-FDG PET myocardial metabolism imaging at the Third Affiliated Hospital of Soochow University from October 2010 to July 2018. The enrollment criteria were: (1) a prior MI greater than 3 months that was confirmed by history, echocardiography, and electrocardiogram (ECG);¹⁵ (2) diagnosed CAD that was defined as single or multiple vessels more than 50% stenosis by coronary angiography (CAG);¹⁶ and (3) severe LV dysfunction, as defined by a left ventricular ejection fraction (LVEF) < 35%. Patients with recent MI, severe arrhythmia, left bundle branch block, or severe valvular disease were excluded. All subjects provided informed consent. The study protocol was approved by the institutional ethics committee of the Third Affiliated Hospital of Soochow University.

Image Acquisition

Gated SPECT MPI

Rest gated SPECT MPI was performed 60–90 minutes after injection of ^99mTc-MIBI (740–925 MBq) in all patients, using a dual-head 90° gamma camera (Symbia T16, Siemens Medical Systems, Erlangen, Germany) equipped with a parallel-hole collimator with low energy and high resolution. The acquisition was gated at 8 frames per R-R cycle with a 20% symmetric energy window around 140-keV photopeak. Sixty-four images covering 180° were obtained with a 64 × 64 matrix and 1.45 magnification. The projection data were reconstructed using filtered back projection (order, 5; cut-off frequency, 0.4) and then reoriented to obtain LV short-axis, horizontal long-axis, and vertical long-axis images. No attenuation correction was used.

¹⁸F-FDG PET

After at least 6 hours of fasting on the following day, all patients underwent ¹⁸F-FDG cardiac PET/CT study. Every patient was given oral glucose of 25–50 g according to their blood glucose levels. Diabetic patients were pretreated with acipimox (500 mg oral dose) before glucose loading. Insulin was intravenously administrated if the blood glucose level > 9 mmol/L at 45 minutes after oral glucose administration. When the serum glucose level reached 5.55–7.77 mmol/L, a weight-adjusted dose of 3 MBq/kg ¹⁸F-FDG was administered intravenously,¹⁷ and followed 1–2 hours later with a standard PET/CT (Biograph mCT 64-s, Siemens Medical Systems, Erlangen, Germany) cardiac imaging protocol. Data were acquired with a matrix of 128 × 128, a magnification of 2, and a photopeak of 511 keV. The images were reconstructed using an iterative algorithm (OSEM, 4 iterations and 8 subsets) and LV short-axis, horizontal long-axis, and vertical long-axis images were obtained.

Image Analysis

Assessment of myocardial viability

SPECT MPI images compared with ¹⁸F-FDG PET images were analyzed and interpreted by two experienced nuclear cardiologists independently and the consensus result was reported. They were blinded to the gated analysis at the time of interpretation. For each patient, a standard 17-segment model¹⁸ was applied to each polar map for segmental analysis. A five-point, semi-quantitative, visual uptake score (0 = normal, 1 = mildly reduced uptake, 2 = moderately reduced uptake, 3 = severely reduced uptake, 4 = absent) of the non-gated images was used to grade ^99mTc-MIBI and ¹⁸F-FDG uptakes in all segments.¹⁹ Segments with a perfusion defect score ≥ 2 and consecutive occurrence in 2 or more slices that persisted in rest MPI was considered as decreased perfusion. Based on the combined perfusion and metabolism information, the following three types of segments were classified: (1) normal myocardium: segments with normal perfusion; (2) SPECT/PET mismatch: segments with decreased perfusion and preserved/relatively increased glucose metabolism (improvement in tracer uptake by one grade or more was considered as SPECT/PET mismatch); (3) SPECT/PET match: segments with decreased perfusion and a concordant decreased glucose metabolism.²⁰ The mismatch represents hibernating myocardium while the match represents scar.^21,22 The segmental perfusion uptake rate, summed rest score (SRS), and total perfusion deficit (TPD) of LV were assessed by an automated cardiac software package (QPS 2009, Cedars-Sinai Medical Center, Los Angeles, CA, USA).

Assessment of regional myocardial function

The QGS software package (QGS 2009, Cedars-Sinai Medical Center, Los Angeles, CA, USA) was used to quantitatively measure LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LVEF, and semi-quantitatively measure segmental wall motion and thickening from gated SPECT MPI. A scale of 0–5 was used to grade segmental wall motion (0 = normal, 1 = mildly hypokinetic, 2 = moderately hypokinetic, 3 = severely hypokinetic, 4 = akinetic, 5 = dyskinetic), and a scale of 0–3 was used to grade segmental wall thickening (0 = normal, 1 = mildly reduced, 2 = moderately to severely reduced, 3 = no thickening).⁹ All segmental function analyses were performed by two independent experienced readers blinded to perfusion/metabolism data.

Statistical Analysis

Data analysis was performed using SPSS software package (IBM SPSS Statistics 21.0, SPSS Inc, Chicago, IL). The metrological data with normal distribution were expressed as mean ± SD. Categorical data were expressed as a percentage and analyzed using chi-square test. Intra- and inter-observer agreements of segmental parameters were assessed by the respective intraclass correlation coefficients (ICCs). Measures of segmental wall motion and thickening in hibernating myocardium and scar were reported. Univariate analysis was conducted to identify statistically significant variables. Then stepwise multivariate analysis (forward LR) was conducted with the multiple logistic regression method using statistically significant variables in the univariate analysis to establish an optimal multivariate model for predicting hibernating myocardium and scar. In addition, the receiver operating characteristic (ROC) curves were drawn by MedCalc software package (MedCalc V.15.2.0, MedCalc Software, Ostend, Belgium) to determine the optimal cut-off values and the area under the curves (AUCs) were compared using the Z-test. Global chi-square statistic by a likelihood ratio test was then used to compare the overall performance of perfusion alone versus combined perfusion/function for detection of myocardial viability in hypoperfused segments. P < 0.05 was considered to be statistically significant.

RESULTS

Patient Characteristics

Eighty-three patients with ischemic heart failure (male, 72; age, 63.4 ± 6.9 years; LVEF, 26.1% ± 6.4%) were included in this study. There were 26 (31.3%) patients with two-vessel disease and 57 (68.7%) with triple-vessel disease. Of the 83 patients, the NYHA classes of 80.7% patients were III to IV. Twenty-two patients (26.5%) had a history of previous PCI, and 15 patients (18.1%) underwent a prior CABG surgery (both > 6 months before the study). 61 patients (73.5%) had hypertension and 16 patients (19.3%) had diabetes, while 28 patients (33.7%) had hyperlipidemia. The enrolled patients’ demographic data and clinical characteristics are listed in Table 1. Table 2 lists the LV perfusion and function parameters obtained by gated SPECT MPI of all patients. Among the 1411 segments evaluated in the enrolled 83 patients, there were 774 segments with normal perfusion, and 637 segments with decreased perfusion. Of the 637 segments with decreased perfusion, there were 338 hibernating segments by SPECT/PET mismatch and 299 scarred segments by SPECT/PET match, as shown in Figure 1.

Table 1.

Characteristics of study population (n = 83)

Characteristics	Value
Age (years old)	63.4±6.9
Male (%)	72 (86.7)
BMI (kg/m2)	24.6±3.1
Hypertension (%)	61 (73.5)
Diabetes (%)	16 (19.3)
Hyperlipidemia (%)	28 (33.7)
NYHA class III–IV (%)	67 (80.7)
Prior PCI (%)	22 (26.5)
Prior CABG (%)	15 (18.1)
Two-vessel disease (%)	26 (31.3)
Triple-vessel disease (%)	57 (68.7)

BMI body mass index, PCI percutaneous coronary intervention, CABG coronary artery bypass graft, NYHA New York Heart Association classification of heart failure

Table 2.

The LV functional parameters of the enrolled patients (n = 83)

Parameters	Value (mean ± SD)
LVEDV (ml)	203.8±80.0
LVESV (ml)	154.0±73.4
LVEF (%)	26.1±6.4
SRS	28.4±11.2
Extent (%)	44.5±15.6
TPD (%)	38.2±14.6

LVEF left ventricular ejection fraction, LVESV left ventricular end-systolic volume, LVEDV left ventricular end-diastolic volume, TPD total perfusion deficit, SRS summed rest score

Figure 1.

Segmental myocardial viability in the enrolled patients (n = 83).

The Intra-observer and Inter-observe Reproducibility of Segmental Perfusion and Function Quantifications

The repeatability of intra-observer was 0.981 for wall motion, 0.991 for wall thickening, and 0.985 for rest perfusion uptake rate (95%CI 0.978–0.984, 0.990–0.993, 0.982–0.987, all P < 0.001), respectively. Furthermore, the inter-observer reproducibility rates for measuring wall motion, wall thickening, and rest perfusion uptake rate were all excellent (ICCs 0.964, 95%CI 0.958–0.969; 0.985, 95%CI 0.983–0.987; and 0.965, 95%CI 0.958–0.970, respectively). The repeatability and reproducibility of segmental parameters are listed in Table 3.

Table 3.

The reproducibility and repeatability of segmental perfusion and function parameters

	Intra-observer			Inter-observer
Parameters	ICC	95%CI	P value	ICC	95%CI	P value
WM	0.981	0.978–0.984	< 0.001	0.964	0.958–0.969	< 0.001
WT	0.991	0.990–0.993	< 0.001	0.985	0.983–0.987	< 0.001
Rest perfusion uptake	0.985	0.982–0.987	< 0.001	0.965	0.958–0.970	< 0.001

ICC intraclass correlation coefficient, CI confidence interval, WM wall motion, WT wall thickening

Univariate and Multivariate Analysis

In the univariate regression model, segmental perfusion uptake rate (OR 0.951, 95%CI 0.937–0.964, P < 0.001), wall motion (OR 1.539, 95%CI 1.348–1.757, P < 0.001), and wall thickening scores (OR 2.269, 95%CI 1.860–2.768, P < 0.001) had significant correlations with myocardial viability in the segments with decreased perfusion. We further established three multivariate models (model 1: Perfusion uptake rate + WM, model 2: Perfusion uptake rate + WT, model 3: Perfusion uptake rate + WT +WM) of these parameters using stepwise logistic regression analysis (adding one variable at a time to perfusion) to predict hibernating myocardium. The results are shown in Table 4.

Table 4.

Univariate and multivariate analysis of segmental perfusion uptake rate, wall motion and thickening scores for the prediction of hibernating myocardium in the segments with decreased perfusion

			Multivariate model 1		Multivariate model 2		Multivariate model 3
	Univariate analysis		Perfusion uptake rate + WM		Perfusion uptake rate + WT		Perfusion uptake rate + WT +WM
Variables (segmental)	OR(95%CI)	P value	OR(95%CI)	P value	OR(95%CI)	P value	OR(95%CI)	P value
Perfusion uptake rate	0.951 (0.937–0.964)	< 0.001	0.958(0.944–0.972)	< 0.001	0.965(0.950–0.979)	< 0.001	0.967(0.952–0.981)	< 0.001
Wall motion (WM)	1.539 (1.348–1.757)	< 0.001	1.430(1.248–1.639)	< 0.001	-	-	1.242(1.072–1.439)	0.004
Wall thickening (WT)	2.269 (1.860–2.768)	< 0.001	-	-	1.983(1.618–2.430)	< 0.001	1.763(1.421–2.186)	< 0.001

WM wall motion, WT wall thickening, CI confidence interval, OR odds ratio

The Value of Rest Perfusion Uptake, Wall Motion and Thickening for Detecting Myocardial Viability

According to the ROC curve, the rest perfusion uptake ≥ 50% had the optimal diagnostic efficacy when all the myocardial segments were divided into viable (consisting of normal and hibernating myocardium) and non-viable myocardium (scar). Furthermore, the optimal cut-off values of wall motion and wall thickening scores are WM ≤ 3 and WT ≤ 2 to discriminate hibernating myocardium from scar in the 637 segments with decreased perfusion. Figure 2 showed the proportion of different scores of WM (A) and WT (B), respectively.

Figure 2.

Distribution of wall motion and thickening scores in hibernating myocardium and scar in the decreased perfusion segments (n = 637) of the enrolled patients. WM (A), wall motion; WT (B), wall thickening.

Incremental Diagnostic Value of Wall Motion and Thickening to Rest Perfusion Uptake Alone for Distinguishing Hibernating and Scarred Segments

As compared to rest perfusion uptake alone, combined myocardial perfusion with wall motion, wall thickening, or both had the significantly increased AUC areas (0.718 vs 0.666, P = 0.0002; 0.744 vs 0.666, P < 0.0001; 0.753 vs 0.666, P < 0.0001), and the latter had the largest C-statistic to discriminate hibernating myocardium from scar in the segments with decreased perfusion, as was shown in Figure 3. Accordingly, compared to the rest perfusion uptake alone, rest perfusion uptake combined with wall motion and thickening improved the diagnostic accuracy from 64.2% to 73.2% (409/637 vs 466/637, P = 0.001). In addition, Figure 4 shows that the addition of segmental wall motion increased the global chi-square from 53.281 to 82.408 (P < 0.001) when compared to perfusion alone, and additional wall thickening resulted in a significant increase in the global chi-square in the prediction of myocardial viability in hypoperfused segments (102.706 vs 53.281, P < 0.001). Subsequently, the model of combined segmental wall motion, thickening analysis, and perfusion data by gated SPECT MPI yielded a further significant increase in the global chi-square (111.234 vs 102.706, 82.408 and 53.281, all P < 0.001). Figure 5 illustrates a patient example.

Figure 3.

Comparison of C-statistic with the addition of wall motion and thickening to rest perfusion uptake for distinguishing hibernating and scarred segments in patients with ischemic heart failure. WM, wall motion; WT, wall thickening; AUC, area under curve.

Figure 4.

Improved diagnostic performance with the addition of wall motion and thickening to rest perfusion uptake in the detection of myocardial viability in patients with ischemic heart failure. *Compared with rest perfusion uptake alone, P<0.0001; ^#Compared with the model of rest perfusion uptake combined with WM, P < 0.0001. WM wall motion, WT wall thickening.

Figure 5.

A patient example. A 64-year-old man had hypertension, type II diabetes, a history of anterior myocardial infarction and severe LV dysfunction (LVEF=34% on echocardiography). He experienced shortness of breath (Class III, NYHA), and had undergone coronary angiography, which showed severe three-vessel disease. A shows rest SPECT MPI images, and B shows ¹⁸F-FDG PET myocardial metabolic images. The left, middle and right columns are LV short-axis, vertical long-axis images, and horizontal long-axis, respectively. A shows perfusion defects of apex, anterior wall, inferior wall and septal wall. B Of segments with significant perfusion defects, only the segments of apex and apical anterior are scar, and the rest are hibernating myocardium with improved FDG uptake. C Myocardial perfusion shows that segments of apex, apical anterior, mid anterior, apical inferior, mid inferior, apical lateral, and septal wall (n =11) in LV had decreased perfusion (< 50%), which represented scar based on perfusion analysis alone in the present study. Using perfusion alone has overestimated scar when compared with the SPECT/PET results. D Wall motion analysis shows that the segments of apex, apical anterior wall, apical septal wall and mid anteroseptal are scars (segmental WM ≥ 4, n = 4), indicating 7 more viable myocardial segments were detected when compared with the SPECT/PET results. E Wall thickening analysis shows that only the segments of apex, apical anterior wall, and apical septal wall are scars (segmental WT = 3, n = 3), indicating 8 more viable myocardial segments were detected, which is closer compared with the SPECT/PET results.

DISCUSSION

In patients with ischemic heart disease, the detection of myocardial viability is of clinical and prognostic importance and may significantly affect therapeutic decisions.^1–3 SPECT MPI seems to be one of the most available and cost-effective methods for assessment of myocardial viability. Previous studies^10,11,23 have developed different perfusion uptake cut-off values to distinguish viable from non-viable (scar) myocardium, and it has been widely accepted that viability is defined by segments with tracer activity greater than 50% using rest MPI images. However, the abnormally contracting segments with perfusion uptake < 50% also contain a substantial amount of hibernating myocardium.^12,13 In this study, we hypothesized that gated SPECT MPI alone, a “one-stop shop” assessment of myocardial function and perfusion, enhances the ability to identify hibernating myocardium in hypoperfused segments of ischemic heart failure patients. The results of the present study support our hypothesis that, in addition to conventional perfusion uptake, myocardial wall motion and thickening scores could provide incremental value for better differentiation of hibernating myocardium from scar in patients with ischemic heart failure.

Previous studies have confirmed that segments with ≥ 50% perfusion uptake can accurately identify viable myocardium.^11,23 Our data confirmed this finding when we divided all the myocardial segments into viable and non-viable myocardium. Maruyam et al.²⁴ reported that the overall accuracy showed no significant difference when combining wall thickening with conventional perfusion data on gated SPECT MPI in 33 patients with old MI. However, different from their study, we found that wall motion and thickening analysis integrated with myocardial perfusion from gated SPECT MPI provided incremental value in detecting myocardial viability. Several reasons may contribute to the difference between these two studies. First, different imaging techniques of MPI were used. Second, wall thickening in their study was calculated as ((counts ES – counts ED)/counts ED) × 100, while our measurement was based on the quantitative score of a well-validated software package with an excellent reproducibility (Table 3). Third, our study was based on a standard 17-segment model, while their study divided LV into 24 segments. Finally, the differences may be due to the definition of the reference standard. Rest SPECT MPI combined with ¹⁸F-FDG PET imaging was used as the reference standard to assess myocardial viability in our study, which is more accurate than the PET uptake alone used in their study. In addition, Bom et al.²⁵ compared gated FDG PET with conventional PET NH₃-FDG in 21 patients with ischemic heart failure and found that gated FDG PET could be a substitute for NH₃-FDG PET in determining myocardial viability. Moody et al.²⁶ sought to define the relationship between ⁸²Rb kinetics and myocardial viability compared with conventional ⁸²Rb and ¹⁸F-FDG perfusion-metabolism PET imaging and demonstrated that both KP and k₂ obtained from ⁸²Rb PET accurately differentiated hibernating myocardium and scar in patients with chronic ischemic cardiomyopathy. However, the medical cost for PET scans are expensive, and the equipment is not extensively available, while SPECT is more widely used and cost-effective for assessment of myocardial viability from the perspective of health economics.

Gated image acquisition adds considerable value to ^99mTc-MIBI SPECT MPI because it can measure both global and regional myocardial function. In the univariate regression model, segmental perfusion uptake rate, wall motion, and wall thickening scores were all significantly related to myocardial viability in the segments with decreased perfusion. It is widely recognized that perfusion uptake rate is directly proportional to the myocardial blood flow and is closely related to the viability of myocardial cells. Besides, abnormal wall motion and thickening are often present in segments with abnormal perfusion.²⁷ A higher correlation between segmental wall thickening and myocardial viability was shown in this study. Pathologic examinations have also demonstrated that myocardial thickening is absent in areas of necrotic myocardium in chronic transmural infarction,²⁸ whereas preserved wall thickness, even if reduced, indicates the viable myocardium.²⁹ Segmental motion is particularly problematic as an infarcted segment may move because it is attached to an un-infarcted segment. An infarcted segment, however, will not thicken. Furthermore, wall thickening expressed as a percentage of end-diastolic wall thickness is less influenced by attenuation and noise than the absolute value of wall thickness because it is a relative value.³⁰ Our results confirmed these findings. The multivariate step-wise logistic regression analysis showed that the model that consists of perfusion uptake rate, wall motion, and thickening scores has the optimum C-statistic and global chi-square to distinguish hibernating myocardium from scar in the segments with decreased perfusion. Therefore, analysis of gated perfusion images for wall motion and thickening abnormalities adds diagnostic information to the assessment of myocardial viability.

In the 338 hibernating myocardium segments, 217 (64.2%) of them had WM ≤ 3, and 247 (73.1%) of them had WT ≤ 2. For 299 scarred segments, 223 (74.6%) of them had WM > 3, and 217 (72.6%) of them had WT = 3. However, there were 76 (25.4%) scarred segments with WM ≤ 3 and 82 (27.4%) with WT ≤ 2. The reason may include: (1) the scarred segments consist of partial hibernating myocardium with preserved wall thickness and contractility; (2) partly due to an attenuation artifact, exhibiting severely reduced perfusion; (3) the infarcted segment may move due to its attachment to the non-infarcted segment. In addition, of the 338 hibernating segments, 121 (35.8%) segments showed WM > 3 and 91 (26.9%) showed WT = 3, which may be because of the wall motion abnormalities and severely reduced wall thickening caused by non-transmural myocardial necrosis.³¹ Therefore, myocardial viability should be considered as a continuum, from full-thickness viability without any scar to full-thickness scarring without viable cells. Our data demonstrate that the commonly accepted concept of ‘‘a reduced number of myocytes taking up tracer’’ in areas of myocardial infarction is only one possible explanation for the presence of myocardial viability in human subjects.

Assessment of myocardial viability is clinically important in patients with ischemic heart failure, as patients with large amounts of viable myocardium are more likely to benefit from revascularization.^{32 18}F-FDG PET is commonly used as the reference standard to evaluate viability. However, although ¹⁸F-FDG PET is an accurate marker of histologic viability, it is expensive, time-consuming, and resource-intensive.³³ Sharma et al.³⁴ found that regional wall thickening measurement by delayed contrast MRI could assess myocardial viability and functional recovery of ischemic cardiomyopathy. Previous studies^35,36 reported that regional myocardial function analysis by rest gated SPECT GMPI predicted reversible LV dysfunction, while both ¹⁸F-FDG PET and PET-SPECT uptake threshold have limitations in the prediction of functional recovery after revascularization assessed by MRI. In this study, we established a multivariate model consisting of myocardial function and perfusion parameters on gated SPECT MPI. It enables better differentiation of hibernating myocardium from scar compared with SPECT/PET myocardial viability as the reference standard in patients with ischemic heart failure. Previous studies^14,35,37 demonstrated that wall motion and thickening analysis by gated SPECT MPI provided additional information for predicting segmental functional recovery after revascularization in CAD patients when compared perfusion data alone, which indicates that the wall motion and thickening are useful markers of myocardial viability. Similarly, our results showed that wall motion and thickening had provided incremental information in detecting myocardial viability, which suggests that additional analysis of regional myocardial function to perfusion may be advantageous, resulting in a better guiding index to revascularization and improve the treatment outcome. The detection of myocardial viability by myocardial function combined with perfusion, if used in clinical settings, could shorten the diagnostic routine, reduce the costs, and decrease radiation exposure to patients and staff.³³ Future studies are needed to validate the accuracy of the combined model for the prediction of functional improvement after revascularization.

Limitations

Several limitations should be acknowledged. First, due to the retrospective design of the present study, no detailed data about prognostic information and functional recovery after treatment can be presented, which needs to be further investigated. However, functional recovery after revascularization is affected by many factors other than viable myocardium, such as the time of hibernating, the means of revascularization, and reperfusion injury. Second, rest SPECT MPI combined with ¹⁸F-FDG PET imaging to assess myocardial viability in this study was not a real gold standard. However, ¹⁸F-FDG PET images are commonly interpreted in combination with SPECT MPI in current clinical practice and can accurately assess the hibernating myocardium and scar. Hence, we used it as the reference standard. Third, since no attenuation correction was performed in SPECT MPI images, and areas of apparently reduced myocardial perfusion due to soft tissue attenuation may result in the appearance of perfusion-metabolism mismatch and incorrect interpretation,³⁸ comparison of SPECT perfusion images with PET metabolism images should be done carefully. Fourth, we concentrated on differentiating hibernating myocardium and scar in hypoperfused segments, without providing any information about segments with normal perfusion but decreased function, which was reported in our previous study.³⁹ Another potential limitation is that we did not use nitrate enhancement to perform rest imaging for a more effective way to detect myocardial viability. In addition, a variety of MPI imaging modalities have been demonstrated to be useful in the assessment of myocardial viability, such as thallium-201 (Tl-201) rest/redistribution, rest/reinjection imaging protocols, and so on.⁴⁰ However, it has been reported that the image quality of gated Tl-201 SPECT is inferior to ^99mTc-MIBI due to its lower photon energy.⁴¹ Lastly, further studies are also required to elucidate and validate the prognostic value of myocardial viability detected by the integral analysis of myocardial function scores and perfusion on gated SPECT MPI.

CONCLUSIONS

Assessment of myocardial wall motion and thickening in addition to conventional perfusion uptake in the segments with decreased perfusion enables better differentiation of hibernating myocardium from scar in patients with ischemic heart failure. Considering wide availability and high cost-effectiveness, regional myocardial function integrated with perfusion on gated SPECT MPI has great promise to become a clinical tool in the assessment of myocardial viability. However, further study is necessary to evaluate its clinical utility for predicting benefit after revascularization.

NEW KNOWLEDGE GAINED

Our study adds new knowledge on the clinical value of regional myocardial function as wall motion and thickening scores by gated SPECT MPI providing incremental diagnostic value to discriminate hibernating myocardium from scar in patients with ischemic heart failure.

Abbreviations

SPECT

Single-photon emission computed tomography

PET

Positron emission tomography

MPI

Myocardial perfusion imaging

^99mTc-MIBI

^99mTechnetium-sestamibi

¹⁸F-FDG

¹⁸F-deoxyglucose

CAD

Coronary artery disease

LVEDV

Left ventricular end-diastolic volume

LVESV

Left ventricular end-systolic volume

LVEF

Left ventricular ejection fraction

WM

Wall motion

WT

Wall thickening