Usefulness of phase analysis on ECG gated single photon emission computed tomography myocardial perfusion imaging.

Electrocardiogram (ECG)-gated single photon emission computed tomography myocardial perfusion imaging (GSPECT-MPI) is widely used for assessing coronary artery disease. Phase analysis on GSPECT-MPI can assess left ventricular mechanical dyssynchrony quantitatively on standard GSPECT-MPI alongside myocardial perfusion and function assessment. It has been shown that phase variables by GSPECT-MPI correlate well with tissue Doppler imaging by echocardiography. Main phase variables quantified by GSPECT-MPI are entropy, bandwidth, and phase standard deviation. Although those variables are automatically obtained from several software packages including Quantitative Gated SPECT and Emory Cardiac Toolbox, the methods for their measurement vary in each package. Several studies have shown that phase analysis has predictive value for response to cardiac resynchronization therapy and prognostic value for future adverse cardiac events beyond standard GSPECT-MPI variables. In this review, we summarize the basics of phase analysis on GSPECT-MPI and usefulness of phase analysis in clinical practice.

Cardiac remodelling in association with left ventricular dyssynchrony and systolic dysfunction in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease (CAD), ischaemic cardiomyopathy may result in progressive cardiac remodelling and left ventricular (LV) dysfunction. Myocardial perfusion imaging (MPI) can be used to quantify LV size and shape, mechanical dyssynchrony (LVMD) and ejection fraction (EF) as well as myocardial ischaemia and injury extents. We investigated the prevalence of LV remodelling (LVR) in patients with CAD and the relationship between LVR, LVMD and EF. METHODS: Three hundred twenty-six patients with CAD were evaluated. The EF and end-diastolic volume (EDV) were measured using MPI. LVMD was assessed using phase analysis. LVR was characterised according to LV dilatation or increased shape indices (systolic shape index [SIES] and diastolic shape index [SIED]). RESULTS: LVR were observed in 41% of CAD patients. EDV, SIES and SIED were larger in patients with LVMD or low EF. After adjustment for age, sex and infarct and ischaemia extents, phase histogram bandwidth correlated with EDV (r = 0.218) and SIES (r = 0.266) and EF correlated with EDV (r = -0.535), SIES (r = -0.554) and SIED (r = -0.217, p < 0.001 for all). CONCLUSIONS: LVR is frequently seen in patients with CAD and may be detected even before the development of symptomatic heart failure. A large LV volume and a more spherical-shaped LV were associated with LVMD and low EF, highlighting the close relationships between remodelling and systolic dyssynchrony and dysfunction. MPI is useful for assessing LVR by providing information about LV size and shape, which changes from an ellipsoid towards a spherical form in the development of ischaemic cardiomyopathy.

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Effect of left ventricular mechanical dyssynchrony assessed pre-renal transplantation on cardiovascular death post transplantation.

BACKGROUND: SPECT myocardial perfusion imaging (MPI) provides an assessment of LV mechanical dyssynchrony (LVMD) which correlates with CVD outcomes in diverse populations including those awaiting renal transplant (RT). The current study examines the association of LVMD on pre-transplant MPI with long-term CVD mortality post RT. METHODS: We identified consecutive patients who underwent RT at the University of Alabama at Birmingham between 2008 and 2012 from our prospectively collected database. 675 patients in the database underwent MPI and had images amenable for phase analysis. A blinded investigator retrieved the studies and derived LVMD indices including histogram bandwidth (BW), standard deviation (SD), phase peak, phase skewness, and phase kurtosis. The primary outcome was CVD death after RT. RESULTS: The study cohort had a median age of 54 years, 56% were men, 43% had diabetes, and 7% had prior myocardial infarction. Patients were on dialysis for a median of 3.4 years prior to RT and 34% received living donor transplants. During a median follow-up time after RT of 4.7 years (IQR 3.5 to 6.3 years) 59 patients (9%) succumbed to CVD death. Patients with wider BW, wider SD, lower skewness, and lower kurtosis had an increased risk of CVD death. On multivariate adjustment, BW and skewness remained as independent predictors of CVD deaths. CONCLUSIONS: LVMD by phase analysis of gated SPECT MPI is associated with increased risk of CVD death after RT. This association is independent of demographics, comorbidities, and traditional findings on MPI and added incremental prognostic information. Assessment of LVMD should be considered for risk stratification in these patients.

Prognostic value of left ventricular mechanical dyssynchrony induced by exercise stress in patients with normal myocardial perfusion single-photon emission computed tomography.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. METHODS: We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). RESULTS: During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs. CONCLUSIONS: LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.

Comparing left ventricular mechanical dyssynchrony between diabetic and non-diabetic patients with normal gated SPECT MPI.

The aim of this study was to employ phase analysis to diagnose left ventricular mechanical dyssynchrony (LVMD) in asymptomatic patients with diabetes mellitus type 2 and normal perfusion study which may help prevent diabetic cardiomyopathy. Ninety-three consecutive patients with known type 2 diabetes and 81 age- and gender- matched patients without diabetes who were candidates for SPECT-MPI were considered as the control group. The presence of LVMD as an possible risk factor for cardiomyopathy- was determined using phase analysis for each scan with quantitative gated SPECT (QGS) and corridor4DM (4DM) software. All outcomes such as phase bandwidth (PBW) and phase standard deviation (PSD) were compared between the two groups. A total of 174 patients were included in the study. There were no statistically significant difference regarding demographic factors between the two groups (P > 0.05). PBW showed statistically significant differences (increased in diabetics) between the control and diabetic patients (P < 0.05). Kruskal Wallis analysis revealed that as the duration of diabetes is prolonged, especially more than 15 years, the probability of LVMD is increased as well (P = 0.021). Fraction of asymptomatic diabetic patients with normal ejection fraction and gated SPECT MPI-especially those with prolonged diabetes- might have some degrees of LVMD. Phase analysis can detect this which in turn may prevent progress into heart failure.

Mechanisms of left ventricular dyssynchrony: A multinational SPECT study of patients with bundle branch block.

BACKGROUND: To better understand the mechanisms of left ventricular (LV) mechanical dyssynchrony (LVMD), we explored the relative contributions of QRS duration (QRSd), LV ejection fraction (EF), volumes and scar to LVMD measured by gated single-photon emission tomography in a population of consecutive patients with left bundle branch block (LBBB) and right bundle branch block (RBBB) compared to controls. METHODS: Myocardial perfusion imaging studies of 275 LBBB and 83 RBBB patients from three centers were analyzed. LVMD was defined as an abnormal phase bandwidth or phase standard deviation. Hospital and gender-specific normal values were obtained from 172 controls. RESULTS: The prevalence of LVMD was 85 and 40% in LBBB and RBBB, respectively. Ejection fraction, scar severity, and LBBB morphology independently explained 70% of variance seen in PhaseBW. Ejection fraction had the highest area under the curve (AUC 0.918) in the receiver operating characteristics analysis of LVMD with an optimal cut-off of 47% (sensitivity 73% and specificity 98%). Notably, QRSd was not predictive. CONCLUSION: LV mechanical dysfunction plays a greater role than conduction abnormality in the genesis of LVMD, a finding that is intriguing in the context of contemporary literature which suggests that QRSd is the parameter that is most predictive of CRT response.

Are SPECT MPI measures of dyssynchrony dyssynchronous?

BACKGROUND: Assessment of left ventricular mechanical dyssynchrony (LVMD) from gated SPECT myocardial perfusion imaging (MPI) aims to aid selection of patients for cardiac resynchronization therapy (CRT), using either the standard deviation of left ventricular phase (PSD) ≥ 43° or phase histogram bandwidth (HBW) of > 38° and > 30.6° in males and females, respectively. We observed dyssynchrony parameters might be affected by test type and alignment. METHODS: We reviewed 242 patients who underwent gated SPECT MPI with use of the Emory Cardiac Toolbox comparing PSD and HBW at rest and stress for Pearson correlation, and substitutability with Bland-Altman analysis. RESULTS: There is statistically significant difference in the mean PSD and HBW during rest vs stress (33.4 ± 17.4° vs 20.7 ± 13.5° and 97.7 ± 59.6° vs 59.4 ± 45.4°, respectively, P < 0.001). Proper valve plane alignment rendered smaller values (i.e., less dyssynchrony) in both phase SD and HBW (16.8 ± 13.5) vs (22.2 ± 14.7) (P = 0.011), and (47.0 ± 38.2) vs (60.7 ± 48.0) (P = 0.023), respectively. CONCLUSION: Proper alignment and test type, particularly low-dose rest vs high-dose stress, should be considered when assessing LVMD using SPECT MPI.

The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction.

BACKGROUND: Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. METHODS AND RESULTS: Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). CONCLUSIONS: Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.

Left ventricular end-systolic contractile entropy can predict cardiac prognosis in patients with complete left bundle branch block.

BACKGROUND: Several patients with complete left bundle branch block (CLBBB) show left ventricular (LV) dyssynchrony and poor cardiac prognosis. However, the prognostic value of LV end-systolic contractile entropy which was measured by single-photon emission computer tomography (SPECT) has not been elucidated in patients with CLBBB. METHODS AND RESULTS: We recruited consecutive 115 sinus-rhythm patients with CLBBB who underwent ECG-gated 201TlCl-SPECT. After 30 days of observation, finally 102 patients (75.2 ± 9.5 years, 62 male) were enrolled and observed retrospectively for a median of 671 days. Twenty-five patients fell into major cardiac events. Multivariate Cox regression analysis showed estimated glomerular filtration rate (eGFR) ≤ 39.35 mL/min and entropy ≥ 79% were significant and independent predictors for major cardiac events (hazard ratio: 4.256 and 7.587, P value = 0.006 and < 0.001, respectively). Machine learning (Random Forest method) revealed eGFR and entropy had higher feature importance than other predictors (0.140 and 0.138, respectively). Kaplan-Meyer curve analysis demonstrated that the group with entropy ≥ 79% and eGFR ≤ 39.36 mL/min had the worst cardiac prognosis (Logrank: P = 0.002). CONCLUSIONS: Left ventricular end-systolic contractile entropy predicts poor cardiac prognosis in patients with CLBBB, which may be more valuable than the other parameters of SPECT.

Effects of upright T-wave in lead aVR on left ventricular volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease.

BACKGROUND: Numerous studies have shown the association between chronic kidney disease (CKD) and adverse cardiac events. We investigated whether or not the upright T-wave in lead aVR (TaVR) could predict left ventricular (LV) volume and function derived from ECG-gated SPECT in patients with advanced CKD. METHODS: Two hundred and sixty-one patients with advanced CKD [estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2] were enrolled. Upright TaVR was defined as a wave with a positive deflection of > 0 mV. Enlarged LV end-diastolic volume (LVEDV) was defined as LVEDV index of > 76 ml/m2 in men and > 57 ml/m2 in women. Reduced LV ejection fraction (LVEF) was defined as LVEF of < 40%. RESULTS: Forty-six patients (18%) had upright TaVR, and 215 patients (82%) had negative TaVR. Summed redistribution score (SRS) [ 6 (1-12) vs. 2 (0-5), p < 0.001] and summed difference score (SDS) [4 (1-6) vs. 2 (0-4), p = 0.004] were significantly larger in patients with upright TaVR than those with negative TaVR. Patients with upright TaVR had larger LVEDV index (75 ± 33 ml/m2 vs. 50 ± 18 ml/m2, p < 0.001) and lower LVEF (43 ± 14% vs. 58 ± 11%, p < 0.001) compared to those with negative TaVR. After adjusted for other variables including SRS and SDS, upright TaVR remained a significant predictor of enlarged LVEDV (odds ratio 5.45; 95% CI 2.16-14.22; p < 0.001) and reduced LVEF (odds ratio 4.54; 95% CI 1.70-12.23; p = 0.003). CONCLUSIONS: Our data suggested that upright TaVR could predict LV volume and function derived from ECG-gated SPECT in patients with advanced CKD.

Left ventricular systolic and diastolic dyssynchrony to improve cardiac resynchronization therapy response in heart failure patients with dilated cardiomyopathy.

BACKGROUND: The systolic and diastolic dyssynchrony is physiologically related, but measure different left ventricular mechanisms. Left ventricular systolic mechanical dyssynchrony (systolic LVMD) has shown significant clinical values in improving cardiac resynchronization therapy (CRT) response in the heart failure patients with dilated cardiomyopathy (DCM). Our recent study demonstrated that LV diastolic dyssynchrony (diastolic LVMD) parameters have important prognostic values for DCM patients. However, there are a limited number of studies about the clinical value of diastolic LVMD for CRT. This study aims to explore the predictive values of both systolic LVMD and diastolic LVMD for CRT in DCM patients. METHODS: Eighty-four consecutive CRT patients with both DCM and complete left bundle branch block (CLBBB) who received gated resting SPECT MPI at baseline were included in the present study. The phase analysis technique was applied on resting gated short-axis SPECT MPI images to measure systolic LVMD and diastolic LVMD, characterized by phase standard deviation (PSD) and phase histogram bandwidth (PBW). CRT response was defined as ≥ 5% improvement of LVEF at 6-month follow-up. Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis. RESULTS: During the follow-up period, 59.5% (50 of 84) patients were CRT responders. The univariate cox regression analysis showed that at baseline QRS duration, non-sustained ventricular tachycardia (NS-VT), systolic PSD, systolic PBW, diastolic PSD, diastolic PBW, scar burden and LV lead in the scarred myocardium were statistically significantly associated with CRT response. The multivariate cox regression analysis showed that QRS duration, NS-VT, systolic PSD, systolic PBW, diastolic PSD, and diastolic PBW were independent predictive factors for CRT response. Furthermore, the rate of CRT response was 94.4% (17 of 18) in patients whose LV lead was in the segments with both the first three late contraction and the first three late relaxation; by contrast, the rate of CRT response was only 6.7% (1 of 15, P < 0.000) in patients whose LV lead was in the segments with neither the first three late contraction nor the first three late relaxation. CONCLUSION: Both systolic LVMD and diastolic LVMD from gated SPECT MPI have important predictive values for CRT response in DCM patients. Pacing at LV segments with both late contraction and late relaxation has potential to increase the CRT response.

Left ventricular mechanical dyssynchrony in patients with chest pain and normal epicardial coronary arteries.

BACKGROUND: To detect ischemia in patients with angina and normal coronaries frequently represents a complex diagnosis. METHODS: To investigate whether left ventricular mechanical dyssynchrony by phase analysis contributes in the evaluation of patients with chest pain and normal coronaries, gated-SPECT myocardial perfusion imaging (MPI) at rest and 30 minutes post-stress was performed in 218 patients with normal epicardial coronaries, who were divided into two groups: those with summed difference score (SDS) ≥ 4 (54 patients, Group 1), and those with SDS < 4 (164 patients, Group 2). Intraventricular synchronism-phase standard deviation (PSD) and histogram bandwidth (HBW)-was evaluated by phase analysis. RESULTS: Women were significantly more frequent in Group 2 (those without ischemia in SPECT MPI): 113 (69%) vs 25 (46%), P = .00001. In males, left ventricular ejection fraction (LVEF) and ventricular volumes were not significantly different between patients with or without ischemia. However, ischemic females showed significantly higher ventricular volumes, minor post-stress LVEF and more negative delta LVEF (- 3.9 vs 0.34, P = .0008) than the non-ischemic ones. There was a significant post-stress increase of PSD and HBW among males, although not among females. According to SSS (≥ 4, with ischemia/necrosis; < 4, without ischemia/necrosis), post-stress PSD and HBW significantly increase both in male and female, and PSD and HBW were significantly higher in females with SSS ≥ 4 compared to those with SSS < 4 (PSD rest: 19.04° vs 11.72°, P < .0001; HBW rest: 58.85° vs 38.21°, P < .0001). PSD and HBW were also higher among males with SSS ≥ 4 compared to those with SSS < 4, although not significantly. CONCLUSION: Higher ventricular volumes in females and dyssynchrony are associated with inducible ischemia in MPI in patients with chest pain and normal coronaries. Stress-induced ischemia increases degree of dyssynchrony.

New approach for quantification of left ventricular function from low-dose gated bloodpool SPECT: Validation and comparison with conventional methods in patients.

BACKGROUND: Planar equilibrium radionuclide angiocardiography (ERNA) has been used as the gold standard for assessment of left ventricular (LV) function for over three decades. However, this imaging modality has recently gained less favor due to growing concerns about radiation exposure. We developed a novel approach that involves integrating short axis slices of gated bloodpool SPECT for quantification of LV function with improved signal-to-noise ratio and reduced radioactive dose while maintaining image quality and quantitative precision. METHODS: Twenty patients referred for ERNA underwent standard in vitro 99mTc-labeling of red blood cells (RBC), and were initially imaged following a low-dose (~ 8 mCi) injection using a dedicated cardiac SPECT camera, and then had planar imaging following a high-dose (~ 25 mCi) injection. Four different quantification methods were utilized to assess the LV function and were compared for quantitative precision and inter-observer reproducibility of the quantitative assessments. RESULTS: The Yale method resulted in the most consistent assessment of LV function compared with the gold standard high-dose ERNA method, along with excellent inter-observer reproducibility. CONCLUSIONS: The new low-dose 99mTc-RBC imaging method provides precise quantification of LV function with a greater than 67% reduction in dose and may potentially improve assessment of regional function.