Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk.

Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.

4D display of CT LV endocardial and epicardial models morphed from PET Rb-82 perfusion studies accurately quantifies segmental myocardial thickening.

BACKGROUND: MPI-derived LV wall thickening assessments for diagnostic purposes has been part of clinical guidelines for two decades. It relies on visual evaluation of tomographic slices or regional quantification displayed in 2D polar maps. 4D displays have not entered clinical usage nor have they been validated on their potential to provide equivalent information. The purpose of this work was to validate a 4D realistic display recently designed to quantitatively represent the thickening information from gated MPI into CT-morphed endocardial and epicardial moving surfaces. METHODS: Forty patients who underwent 82Rb PET were selected based on LV perfusion quantification. CTA templates of heart anatomy were selected to represent the LV anatomy. Generic CT-derived LV endocardial and epicardial surfaces were modified to represent the end diastolic (ED) phase according to PET-derived ED LV dimensions and wall thickness. These CT myocardial surfaces were then morphed by means of thin plate spline (TPS) techniques, according to the gated PET slices count changes (WThPET) and LV wall motion (WMoPET). A geometric thickening (GeoTh) equivalent to LV WThPET was defined on epicardial and endocardial CT surfaces over the cardiac cycle and the two measures compared. WThPET and GeoTh correlations were performed on a case-by-case basis, by segment and by pooling all 17 segments. Pearson's correlation coefficients (PCC) were calculated to assess the equivalence of the two measures. RESULTS: Two cohorts of patients (normal and abnormal) were identified based on SSS. R coefficients were as follows: for all pooled segments PCCstress and PCCrest were respectively 0.91 and 0.89 (normal), and 0.9 and 0.91 (abnormal); when individual 17 segments were considered mean PCCstress = 0.92 [0.81-0.98] and mean PCCrest = 0.93 [0.83-0.98] for the abnormal perfusion group; mean PCCstress = 0.89 [0.78-0.97] and mean PCCrest = 0.89 [0.77-0.97] for the normal. When individual studies were considered, R was always > .70 with the exception of five abnormal studies. Inter-user analysis was also conducted. CONCLUSIONS: Our novel technique for the visualization of LV wall thickening by means of 4D CT endocardial and epicardial surface models accurately replicated 82Rb slice thickening results showing promise for its usage for diagnostic purposes.

Quantitation of diffuse myocardial ischemia with mental stress and its association with cardiovascular events in individuals with recent myocardial infarction.

Microcirculatory dysfunction during psychological stress may lead to diffuse myocardial ischemia. We developed a novel quantification method for diffuse ischemia during mental stress (dMSI) and examined its relationship with outcomes after a myocardial infarction (MI). We studied 300 patients ≤ 61 years of age (50% women) with a recent MI. Patients underwent myocardial perfusion imaging with mental stress and were followed for 5 years. dMSI was quantified from cumulative count distributions of rest and stress perfusion. Focal ischemia was defined in a conventional fashion. The main outcome was a composite outcome of recurrent MI, heart failure hospitalizations, and cardiovascular death. A dMSI increment of 1 standard deviation was associated with a 40% higher risk for adverse events (HR 1.4, 95% CI 1.2-1.5). Results were similar after adjustment for viability, demographic and clinical factors and focal ischemia. In sex-specific analysis, higher levels of dMSI (per standard deviation increment) were associated with 53% higher risk of adverse events in women (HR 1.5, 95% CI 1.2-2.0) but not in men (HR 0.9, 95% CI 0.5-1.4), P 0.001. A novel index of diffuse ischemia with mental stress was associated with recurrent events in women but not in men after MI.

Indicators of abnormal PET coronary flow capacity in detecting cardiac ischemia.

Coronary flow capacity (CFC) categorizes severity of left ventricular (LV) ischemia by PET myocardial blood flow (MBF). Our objective was to correlate abnormal CFC with other indicators of regional ischemia. Data were examined retrospectively for 231 patients evaluated for known/suspected CAD who underwent rest and regadenoson-stress 82Rb PET/CT. MBF and myocardial flow reserve (MFR) were quantified, from which CFC was categorized as Normal CFC (1), Minimally reduced (2), Mildly reduced (3), Moderately reduced (4), and Severely reduced (5) for the three main arterial territories as well as globally. Relative perfusion summed stress score (SSS) and systolic phase contraction bandwidth (BW) were assessed. Accuracy to detect arteries with CFC ≥ 4 was highest for a Regional Index combining SSS and BW (88 ± 3%). A Global Index formed from stress ejection fraction, SSS and BW was the most accurate means of identifying patients with global CFC ≥ 4 (84 ± 3%). Arteries with abnormal CFC derived from absolute myocardial blood flow measurements are accurately identified by composite parameters combining regionally aberrant relative perfusion patterns and asynchrony.

Left Ventricular Strain from Myocardial Perfusion PET Imaging: Method Development and Comparison to 2-Dimensional Echocardiography.

This study aimed to develop a measure of longitudinal, radial, and circumferential myocardial strain at rest and regadenoson during pharmacologic stress using 82Rb PET electrocardiography-gated myocardial perfusion imaging (MPI). Methods: We retrospectively identified 80 patients who underwent rest and regadenoson-stress CT attenuation-corrected 82Rb PET and had a standard resting transthoracic echocardiogram (TTE) with global longitudinal strain (GLS) analysis within 3 mo. A method was developed to compute longitudinal, radial, and circumferential strain from PET MPI at stress and rest. PET MPI-derived strain and left ventricular function were compared with resting TTE measures as the clinical reference standard. Interobserver agreement of PET MPI strain and left ventricular ejection fraction processing was reported. Results: Longitudinal strain assessed with resting TTE GLS showed good correlation with PET MPI at stress (r = 0.68, P < 0.001) and rest (r = 0.58, P < 0.001). Resting TTE GLS also correlated with PET MPI radial strain at stress (r = -0.70, P < 0.001) and rest (r = -0.59, P < 0.001) and circumferential strain at stress (r = 0.67, P < 0.001) and rest (r = 0.69, P < 0.001). The left ventricular ejection fraction showed good correlation between resting TTE and PET MPI at stress (r = 0.83, P < 0.001) and rest (r = 0.80, P < 0.001). Bland-Altman analysis indicated positive bias of TTE GLS compared with PET MPI longitudinal strain at stress (mean difference = 5.1%, 95% CI = [-2.5, 12.7]) and rest (mean difference = 4.2%, 95% CI = [-4.3, 12.8]). Reproducibility of PET MPI longitudinal strain showed good agreement at stress (concordance correlation coefficient = 0.73, P < 0.001) and rest (concordance correlation coefficient = 0.74, P < 0.001), with Bland-Altman analysis showing a small bias in the longitudinal direction at stress (mean difference = -0.2%) and rest (mean difference = -1.0%). Conclusion: Strain measured with PET MPI using an automated technique correlated well with resting GLS strain obtained by TTE, and the measure is reproducible. Strain from PET MPI should be investigated further to establish reference ranges and assess its value in routine clinical practice.

Clinically viable myocardial CCTA segmentation for measuring vessel-specific myocardial blood flow from dynamic PET/CCTA hybrid fusion.

BACKGROUND: Positron emission tomography (PET)-derived LV MBF quantification is usually measured in standard anatomical vascular territories potentially averaging flow from normally perfused tissue with those from areas with abnormal flow supply. Previously we reported on an image-based tool to noninvasively measure absolute myocardial blood flow at locations just below individual epicardial vessel to help guide revascularization. The aim of this work is to determine the robustness of vessel-specific flow measurements (MBFvs) extracted from the fusion of dynamic PET (dPET) with coronary computed tomography angiography (CCTA) myocardial segmentations, using flow measured from the fusion with CCTA manual segmentation as the reference standard. METHODS: Forty-three patients' 13NH3 dPET, CCTA image datasets were used to measure the agreement of the MBFvs profiles after the fusion of dPET data with three CCTA anatomical models: (1) a manual model, (2) a fully automated segmented model and (3) a corrected model, where major inaccuracies in the automated segmentation were briefly edited. Pairwise accuracy of the normality/abnormality agreement of flow values along differently extracted vessels was determined by comparing, on a point-by-point basis, each vessel's flow to corresponding vessels' normal limits using Dice coefficients (DC) as the metric. RESULTS: Of the 43 patients CCTA fully automated mask models, 27 patients' borders required manual correction before dPET/CCTA image fusion, but this editing process was brief (2-3 min) allowing a 100% success rate of extracting MBFvs in clinically acceptable times. In total, 124 vessels were analyzed after dPET fusion with the manual and corrected CCTA mask models yielding 2225 stress and 2122 rest flow values. Forty-seven vessels were analyzed after fusion with the fully automatic masks producing 840 stress and 825 rest flow samples. All DC coefficients computed globally or by territory were ≥ 0.93. No statistical differences were found in the normal/abnormal flow classifications between manual and corrected or manual and fully automated CCTA masks. CONCLUSION: Fully automated and manually corrected myocardial CCTA segmentation provides anatomical masks in clinically acceptable times for vessel-specific myocardial blood flow measurements using dynamic PET/CCTA image fusion which are not significantly different in flow accuracy and within clinically acceptable processing times compared to fully manually segmented CCTA myocardial masks.

18F-flurpiridaz positron emission tomography segmental and territory myocardial blood flow metrics: incremental value beyond perfusion for coronary artery disease categorization.

AIMS: We determined the feasibility and diagnostic performance of segmental 18F-flurpiridaz myocardial blood flow (MBF) measurement by positron emission tomography (PET) compared with the standard territory method, and assessed whether flow metrics provide incremental diagnostic value beyond relative perfusion quantitation (PQ). METHODS AND RESULTS: All evaluable pharmacological stress patients from the Phase III trial of 18F-flurpiridaz were included (n = 245) and blinded flow metrics obtained. For each coronary territory, the segmental flow metric was defined as the lowest 17-segment stress MBF (SMBF), myocardial flow reserve (MFR), or relative flow reserve (RFR) value. Diagnostic performances of segmental and territory MBF metrics were compared by receiver operating characteristic (ROC) areas under the curve (AUC). A multiple logistic model was used to evaluate whether flow metrics provided incremental diagnostic value beyond PQ alone. The diagnostic performances of segmental flow metrics were higher than their territory counterparts; SMBF AUC = 0.761 vs. 0.737; MFR AUC = 0.699 vs. 0.676; and RFR AUC = 0.716 vs. 0.635, respectively (P < 0.001 for all). Similar results were obtained for per-vessel coronary artery disease (CAD) ≥70% stenosis categorization and per-patient analyses. Combinatorial analyses revealed that only SMBF significantly improved the diagnostic performance of PQ in CAD ≥50% stenoses, with PQ AUC = 0.730, PQ + segmental SMBF AUC = 0.782 (P < 0.01), and PQ + territory SMBF AUC = 0.771 (P < 0.05). No flow metric improved diagnostic performance when combined with PQ in CAD ≥70% stenoses. CONCLUSION: Assessment of segmental MBF metrics with 18F-flurpiridaz is feasible and improves flow-based epicardial CAD detection. When combined with PQ, only SMBF provides additive diagnostic performance in moderate CAD.

Clinical implications of compromised 82Rb PET data acquisition.

BACKGROUND: We wished to document the prevalence and quantitative effects of compromised 82Rb PET data acquisitions on myocardial flow reserve (MFR). METHODS AND RESULTS: Data were analyzed retrospectively for 246 rest and regadenoson-stress studies of 123 patients evaluated for known or suspected CAD. An automated injector delivered pre-determined activities of 82Rb. Automated quality assurance algorithms identified technical problems for 7% (9/123) of patients. Stress data exhibited 2 instances of scanner saturation, 1 blood peak detection, 1 blood peak width, 1 gradual patient motion, and 2 abrupt patient motion problems. Rest data showed 1 instance of blood peak width and 2 abrupt patient motion problems. MFR was lower for patients with technical problems flagged by the quality assurance algorithms than those without technical problems (1.5 ± 0.5 versus 2.1 ± 0.7, P = 0.01), even though rest and stress ejection fraction, asynchrony and relative myocardial perfusion measures were similar for these two groups (P > 0.05), suggesting that MFR accuracy was adversely affected by technical errors. CONCLUSION: It is important to verify integrity of 82Rb data to ensure MFR computation quality.

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

BACKGROUND: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs. METHODS: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively. RESULTS: Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant. CONCLUSIONS: Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.

Development, diagnostic performance, and interobserver agreement of a 18F-flurpiridaz PET automated perfusion quantitation system.

BACKGROUND: Computerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process. METHODS: To develop an automated relative perfusion quantitation approach for 18F-flurpiridaz, PET MPI studies from all phase III trial participants of 18F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients. RESULTS: Both approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads. CONCLUSIONS: Our automated method of 18F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.

Early onset of left ventricular regional asynchrony in arteries with sub-clinical stenosis.

BACKGROUND: Asynchrony has been reported to be a marker of ischemic-induced left ventricular dysfunction, the magnitude of which correlates with extent of epicardial coronary disease. We wished to determine whether normal-appearing arterial territories with mild degrees of asynchrony have lower 82Rb PET absolute myocardial blood flow (MBF) and/or lower myocardial flow reserve (MFR). METHODS AND RESULTS: Data were examined retrospectively for 105 patients evaluated for known/suspected CAD who underwent rest/regadenoson-stress 82Rb PET/CT and quantitative coronary angiography. Rest and stress absolute MBF and MFR were quantified from first-pass 82Rb PET curves. Regional relative myocardial perfusion summed stress score (SSS), summed rest score (SRS), regional phase bandwidth (BW), and regional semi-quantitative asynchrony visual scores of (Asynch) were assessed. We found that in apparently normal arteries (SSS < 4, SRS < 4 and stenosis < 70%), those with abnormally low MFR < 2.0 compared to those with MFR ≥ 2.0 had larger phase BW (186 ± 79° vs 158 ± 67°, P = .02), and more visually apparent Asynch (5.7 ± 4.2 vs 3.9 ± 3.6, P = .02), which was associated with increasing stenosis values (ρ = 0.44, P < .0001). CONCLUSION: A subgroup of coronary territories with normal relative perfusion and normal or non-obstructive coronary disease may have reduced MFR, which is signaled physiologically by a mild degree of left ventricular asynchrony.

Diagnostic performance of an artificial intelligence-driven cardiac-structured reporting system for myocardial perfusion SPECT imaging.

OBJECTIVES: To describe and validate an artificial intelligence (AI)-driven structured reporting system by direct comparison of automatically generated reports to results from actual clinical reports generated by nuclear cardiology experts. BACKGROUND: Quantitative parameters extracted from myocardial perfusion imaging (MPI) studies are used by our AI reporting system to generate automatically a guideline-compliant structured report (sR). METHOD: A new nonparametric approach generates distribution functions of rest and stress, perfusion, and thickening, for each of 17 left ventricle segments that are then transformed to certainty factors (CFs) that a segment is hypoperfused, ischemic. These CFs are then input to our set of heuristic rules used to reach diagnostic findings and impressions propagated into a sR referred as an AI-driven structured report (AIsR). The diagnostic accuracy of the AIsR for detecting coronary artery disease (CAD) and ischemia was tested in 1,000 patients who had undergone rest/stress SPECT MPI. RESULTS: At the high-specificity (SP) level, in a subset of 100 patients, there were no statistical differences in the agreements between the AIsr, and nine experts' impressions of CAD (P = .33) or ischemia (P = .37). This high-SP level also yielded the highest accuracy across global and regional results in the 1,000 patients. These accuracies were statistically significantly better than the other two levels [sensitivity (SN)/SP tradeoff, high SN] across all comparisons. CONCLUSIONS: This AI reporting system automatically generates a structured natural language report with a diagnostic performance comparable to those of experts.

Vessel-specific quantification of absolute myocardial blood flow, myocardial flow reserve and relative flow reserve by means of fused dynamic 13NH3 PET and CCTA: Ranges in a low-risk population and abnormality criteria.

OBJECTIVES: The goal of the present work is to present a novel methodology for the extraction of MBF, MFR and RFR along coronary arteries by means of multimodality image fusion of dynamic PET and CCTA images. BACKGROUND: FFR is the reference standard to identify flow-limiting lesions, but its invasiveness limits broad application. New noninvasive methodologies are warranted to stratify patients and guide treatment. METHODS: A group of 16 low-risk CAD subjects who underwent both 13NH3 PET and CCTA were analyzed. Image fusion techniques were employed to align the studies and CCTA-derived anatomy used to identify coronaries trajectories. MBF was calculated by means of a 1-tissue compartmental model for the standard vascular territories and along patient-specific vessel paths from the base to the apex of the heart. RESULTS: Low-risk ranges for MBF. MFR and RFR for LAD, LCX and rPDA were computed for the entire cohort and separated by gender. Computed low-risk ranges were used to assess a prospective patient with suspected CAD. CONCLUSIONS: Our vessel-specific functional indexes and 3D displays offer promise to more closely replicate what is commonly performed during a catheterization session and have the potential of providing effective noninvasive tools for the identification of flow-limiting lesions and image-guided therapy.

Diagnostic performance of the quantification of myocardium at risk from MPI SPECT/CTA 2G fusion for detecting obstructive coronary disease: A multicenter trial.

BACKGROUND: The effective non-invasive identification of coronary artery disease (CAD) and its proper referral for invasive treatment are still unresolved issues. We evaluated our quantification of myocardium at risk (MAR) from our second generation 3D MPI/CTA fusion framework for the detection and localization of obstructive coronary disease. METHODS: Studies from 48 patients who had rest/stress MPI, CTA, and ICA were analyzed from 3 different institutions. From the CTA, a 3D biventricular surface of the myocardium with superimposed coronaries was extracted and fused to the perfusion distribution. Significant lesions were identified from CTA readings and positioned on the fused display. Three estimates of MAR were computed on the 3D LV surface on the basis of the MPI alone (MARp), the CTA alone (MARa), and the fused information (MARf). The extents of areas at risk were used to generate ROC curves using ICA anatomical findings as reference standard. RESULTS: Areas under the ROC curve (AUC) for CAD detection using MARf was 0.88 (CI = 0.75-0.95) and for MARp and MARa were, respectively 0.82 (CI = 0.69-0.92) and 0.75 (CI = 0.60-0.86) using the ≥70% stenosis criterion. AUCs for CAD localization (all vessels) using MARf showed significantly higher performance than either MARa or MARp or both. CONCLUSIONS: Using ICA as the reference standard, MAR as the quantitative parameter, and AUC to measure diagnostic performance, MPI-CTA fusion imaging provided incremental diagnostic information compared to MPI or CTA alone for the diagnosis and localization of CAD.

Rb-82 PET/CT left ventricular mass-to-volume ratios.

Left ventricular (LV) mass:volume ratios indexed to body size (Mi/Vi) provide risk stratification for cardiac events. We sought to determine whether Rb-82 PET mass and volume indices are similar to MRI normal values for low likelihood subjects, and whether abnormal indices are related to abnormal myocardial blood flow (MBF). Data were analyzed retrospectively for 194 patients referred for rest/stress Rb-82 PET. LV EF, volume and mass values were calculated and mass:volume ratios were indexed to patients' height and weight. MBF was computed from the first pass dynamic component of PET data. 53 patients at low likelihood of CAD had PET Mi/Vi = 1.35 ± 0.27, consistent with the MRI literature range of 1.0-1.5. Compared to patients with normal indexed volume (Vi), patients with abnormally high Vi had lower rest MBF (0.56 ± 0.24 vs 0.93 ± 0.57 ml/g/min, p = 0.0001), and lower stress MBF (0.97 ± 0.52 vs. 1.83 ± 0.96 ml/g/min, p < 0.0001). Stress EF < 50% predicted abnormal Vi with 90% accuracy. Patients with Mi/Vi < 1.0 had abnormally low rest EF (45 ± 16% vs. 60 ± 15%, p < 0.0001) and low rest MBF (0.58 ± 0.25 vs. 0.96 ± 0.59 ml/g/min, p < 0.0001). In our study population, abnormal LV volume and mass correlated with lower rest and stress MBF and EF, suggesting that the pathophysiologic explanation of these patients' increased risk is more extensive obstructive CAD.

Relationships between left ventricular asynchrony and myocardial blood flow.

OBJECTIVE: 82Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration. METHODS: We retrospectively analyzed 82Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above 82Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges. RESULTS: Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%). CONCLUSION: LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.

Left ventricular mechanical synchrony from stress and rest 82Rb PET myocardial perfusion ECG-gated studies: differentiating normal from LBBB patients.

BACKGROUND: We have previously reported normal values for LV mechanical synchrony from post-stress exercise (99m)Tc SPECT studies; the goal of this study was to develop normal values for mechanical synchrony from pharmacologic stress and rest (82)Rb PET studies and compare these values to a population of LBBB patients. METHODS AND RESULTS: The normal population consisted of 40 patients with a low likelihood of coronary artery disease. The LBBB population consisted of 23 patients with ECG evidence of LBBB. All patients were imaged with pharmacologic stress and processed using SyncTool™ (Emory Cardiac Toolbox™). Means and standard deviations were calculated for the stress and rest phase parameters. Normal male and female phase standard deviation were 15.0 ± 7.0 and 13.2 ± 7.7, respectively, for stress (P = NS), and 22.7 ± 13.2 and 16.6 ± 14.3 for rest (P = NS). Normal male and female histogram bandwidth were 38.1 ± 13.3 and 32.0 ± 13.5, respectively, for stress (P = NS) and 50.8 ± 18.7 and 44.4 ± 44.9 for rest (P = NS). ROC analysis yielded a sensitivity/specificity as high as 80%/90% for males, and 92%/75% for females (P = NS). CONCLUSIONS: Normal values for LV mechanical synchrony have been developed for (82)Rb pharmacologic stress and rest PET studies; furthermore, the stress pharmacologic values do not differ significantly from our previously reported exercise post-stress SPECT normal values. Finally, ROC analysis confirmed that these normal values were able to differentiate normal and LBBB populations.