A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSION: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Study of Attenuation Correction Using a Cardiac Dynamic Phantom: Synchronized Time-Phase-Gated Attenuation Correction Method.

In cardiac nuclear medicine examinations, absorption in the body is the main factor in the degradation of the image quality. The Chang and external source methods were used to correct for absorption in the body. However, fundamental studies on attenuation correction for electrocardiogram (ECG)-synchronized CT imaging have not been performed. Therefore, we developed and improved an ECG-synchronized cardiac dynamic phantom and investigated the synchronized time-phase-gated attenuation correction (STPGAC) method using ECG-synchronized SPECT and CT images of the same time phase. Methods: As a basic study, SPECT was performed using synchronized time-phase-gated (STPG) SPECT and non-phase-gated (NPG) SPECT. The attenuation-corrected images were, first, CT images with the same time phase as the ECG waveform of the gated SPECT acquisition (with CT images with the ECG waveform of the CT acquisition as the reference); second, CT images with asynchronous ECG; third, CT images of the 75% region; and fourth, CT images of the 40% region. Results: In the analysis of cardiac function in the phantom experiment, left ventricle ejection fraction (heart rate, 11.5%-13.4%; myocardial wall, 49.8%-55.7%) in the CT images was compared with that in the STPGAC method (heart rate, 11.5%-13.3%; myocardial wall, 49.6%-55.5%), which was closer in value to that of the STPGAC method. In the phantom polar map segment analyses, none of the images showed variability (F (10,10) < 0.5, P = 0.05). All images were correlated (r = 0.824-1.00). Conclusion: In this study, we investigated the STPGAC method using a SPECT/CT system. The STPGAC method showed similar values of cardiac function analysis to the CT images, suggesting that the STPGAC method accurately reconstructed the distribution of blood flow in the myocardial region. However, the target area for attenuation correction of the heart region was smaller than that of the whole body, and changing the gated SPECT conditions and attenuation-corrected images did not affect myocardial blood flow analysis.

Relationship between transient ischemic dilatation and changes in heart rate during gated SPECT acquisition in a low-risk population without perfusion defects.

OBJECTIVES: Transient ischemic dilatation (TID) in myocardial perfusion single photon emission computed tomography (SPECT) is considered a marker of poor prognosis. However, it has been suggested that some cases are due to apparent volumetric changes secondary to differences in heart rate (HR) at the time of acquisition. We assessed the correlation between transient dilatation and HR in low risk patients with no perfusion defects. METHODS: We retrospectively analyzed patients sent for 99mTc-MIBI SPECT using a 2-day protocol. We recorded the median HR during acquisition and the HR difference (HRD) between the rest and post-stress. We obtained the medium ventricular volume, end-diastolic volume (EDV), and end-systolic volume (ESV). We included patients in which TID using medium ventricular volume (TIDMV) was ≥1.2. TID was also calculated for the EDV and ESV (TIDEDV, TIDESV). We excluded patients with known coronary artery disease, perfusion defects, various ECG disorders, positive stress test, or ESV < 10 ml. RESULTS: From a total of 2006 patients, 63 (50 exercise, 13 dipyridamole) met the criteria for analysis (age 63.8 ±â€…9.7, 44 men). TIDMV was 1.29 ±â€…0.09 and HRD 9.8 beats per minute (BPM) (range -10 to 41). There was positive correlation between HRD and TIDMV ( r  = 0.51, P  < 0.001) and TIDEDV ( r  = 0.5, P  < 0.001), but not TIDESV ( r  = 0.23, P  = 0.07). Correlation was stronger when HRD was ≥10 BPM ( r  = 0.67, P  < 0.001). CONCLUSION: TID without perfusion defects should be interpreted with caution in the presence of HRD ≥ 10 BPM during post-stress acquisition.

Prognostic value of left ventricular mechanical dyssynchrony indices derived from gated myocardial perfusion SPECT in coronary artery disease: a systematic review and meta-analysis.

PURPOSE: Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor in coronary artery disease. A growing body of evidence indicates that LVMD parameters derived from phase analysis of gated myocardial SPECT may allow risk stratification for future cardiac events. We performed a systematic review and meta-analysis on the prognostic value of LVMD on gated SPECT in patients with coronary artery disease. METHODS: PubMed, Embase, and the Cochrane library were searched until August 25, 2022, for studies reporting the prognostic value of LVMD on gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE) in patients with coronary artery disease. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. RESULTS: Nine studies (26,750 patients) were included in a qualitative synthesis. Among the SPECT LVMD parameters used in various studies, high phase standard deviation, phase bandwidth, and phase entropy were widely evaluated and reported to be associated with high rates of all-cause death, cardiac death, or MACE. For five studies (23,973 patients) in the quantitative synthesis, the pooled HR of LVMD for predicting MACE was 2.81 (95% CI 2.03-3.88). Studies using combined phase parameters to define LVMD showed higher HRs than a study using phase entropy (p = 0.0180). CONCLUSION: LVMD from gated myocardial SPECT is a significant prognostic factor for coronary artery disease. Phase analysis of gated SPECT may be useful for accurate risk stratification and could be applied for clinical decision-making in such patients.

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.

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.

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.

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.

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.

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.