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.

Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease.

BACKGROUND: Flurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES: The purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). METHODS: In this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. RESULTS: A total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m2, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. CONCLUSIONS: This second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273).

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.

A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support.

PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.

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.

Computer assisted interpretation of Tc-99m mercaptoacetyltriglycine diuretic scintigraphy enhances resident performance.

OBJECTIVE: iRENEX is a software module that incorporates scintigraphic and clinical data to interpret 99m Tc- mercaptoacetyltriglycine (MAG3) diuretic studies and provide reasons for their conclusions. Our objectives were to compare iRENEX interpretations with those of expert physicians, use iRENEX to evaluate resident performance and determine if iRENEX could improve the diagnostic accuracy of experienced residents. METHODS: Baseline and furosemide 99m Tc-MAG3 acquisitions of 50 patients with suspected obstruction (mean age ± SD, 58.7 ±â€…15.8 years, 60% female) were randomly selected from an archived database and independently interpreted by iRENEX, three expert readers and four nuclear medicine residents with one full year of residency. All raters had access to scintigraphic data and a text file containing clinical information and scored each kidney on a scale from +1.0 to -1.0. Scores ≥0.20 represented obstruction with higher scores indicating greater confidence. Scores +0.19 to -0.19 were indeterminate; scores ≤-0.20 indicated no obstruction. Several months later, residents reinterpreted the studies with access to iRENEX. Receiver operating characteristic (ROC) analysis and concordance correlation coefficient (CCC) quantified agreement. RESULTS: The CCC among experts was higher than that among residents, 0.84, versus 0.39, respectively, P  < 0.001. When residents reinterpreted the studies with iRENEX, their CCC improved from 0.39 to 0.73, P  < 0.001. ROC analysis showed significant improvement in the ability of residents to distinguish between obstructed and non-obstructed kidneys using iRENEX ( P  = 0.036). CONCLUSION: iRENEX interpretations were comparable to those of experts. iRENEX reduced interobserver variability among experienced residents and led to better agreement between resident and expert interpretations.

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.

Preparing for the Artificial Intelligence Revolution in Nuclear Cardiology.

A major opportunity in nuclear cardiology is the many significant artificial intelligence (AI) applications that have recently been reported. These developments include using deep learning (DL) for reducing the needed injected dose and acquisition time in perfusion acquisitions also due to DL improvements in image reconstruction and filtering, SPECT attenuation correction using DL without need for transmission images, DL and machine learning (ML) use for feature extraction to define myocardial left ventricular (LV) borders for functional measurements and improved detection of the LV valve plane and AI, ML, and DL implementations for MPI diagnosis, prognosis, and structured reporting. Although some have, most of these applications have yet to make it to widespread commercial distribution due to the recency of their developments, most reported in 2020. We must be prepared both technically and socio-economically to fully benefit from these and a tsunami of other AI applications that are coming.

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.

Integrating artificial intelligence and natural language processing for computer-assisted reporting and report understanding in nuclear cardiology.

Natural language processing (NLP) offers many opportunities in Nuclear Cardiology. These opportunities include applications in converting nuclear cardiology imaging reports to digital searchable information that may be used as Big Data for machine learning and registries. Another major NLP application is, with the support of AI, in automatically translating MPI image features directly into nuclear cardiology reports. This review describes the symbiotic relationship between AI and NLP in that NLP is being used to facilitate AI applications and, AI techniques are being used to facilitate NLP. This article reviews the fundamentals of NLP and describes various conventional and AI techniques that have been applied in imaging. Key nuclear cardiology applications are reviewed such as conversion of MPI free-text reports to digital documents as well as direct conversion of MPI images into structured medical reports.

Obstructive sleep apnea, myocardial perfusion and myocardial blood flow: A study of older male twins.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with incidence of cardiovascular disease and with nocturnal angina, but evidence of a link with coronary atherosclerosis and myocardial ischemia is limited and previous studies may have been affected by selection bias or unmeasured confounding factors. METHODS: We performed overnight polysomnography in 178 older male twins. The Apnea/Hypopnea Index (AHI) was calculated to assess OSA from the overnight sleep evaluation. AHI ≥15 was used as indicator of moderate/severe OSA. The following day, twins underwent myocardial perfusion imaging with [82Rb]-chloride positron emission tomography. Quantitative and semiquantitative measures of myocardial perfusion and absolute myocardial blood flow were obtained. RESULTS: The mean age was 68 years and 40% of the sample had an AHI≥15, which indicates moderate to severe OSA. Abnormal myocardial perfusion, both with stress and at rest, was more common in twins with elevated AHI. After adjusting for clinical, lifestyle and behavioral factors, and previous history of cardiovascular disease, twins with AHI ≥15 had 3.6 higher odds (95% CI, 1.5-8.9) of an abnormal total severity score, defined as a score ≥100, and for each 5-point increment in AHI, the odds of abnormality increased by 20% (95% CI, 7%-34%). Twin pairs where both twins had OSA exhibited the greatest risk. There were no differences in measures of ischemia and absolute myocardial blood flow and flow reserve by AHI status. CONCLUSIONS: OSA is associated with myocardial perfusion abnormalities that suggest prior subclinical myocardial scarring or infarction. Early environmental factors that affect both twins equally may play a role and should be further explored.

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.

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

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.

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

PURPOSE: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response. METHODS: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR). RESULTS: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01). CONCLUSION: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.

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.

Incremental value of left ventricular shape parameters measured by gated SPECT MPI in predicting the super-response to CRT.

BACKGROUND: The purpose of this study was to evaluate the predictive value of left ventricular (LV) shape parameters measured by gated SPECT myocardial perfusion imaging (MPI) in super-responders enrolled in the VISION-CRT trial. METHODS: One hundred and ninety-nine patients who met standard criteria for CRT from multiple centers were enrolled in this study. End-systolic eccentricity (ESE) and end-diastolic eccentricity (EDE) were measures of LV shape. Super-responders were the patients who had a relative increase in left ventricular ejection fraction (LVEF) ≥ 15%. RESULTS: Complete data were obtained in 165 patients, and 43.6% of them were classified as super-responders. ESE was an independent predictor of CRT super-responders in univariate (OR 12.59, 95% CI 1.56-101.35, P = .017) and multivariate analysis (OR 35.71, 95% CI 1.66-766.03, P = .006). ESE had an incremental value over significant clinical and SPECT imaging variables, including angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker, coronary artery disease, myocardial infarction, LVEF, end-diastolic volume index, and scar burden (AUC 0.82 vs. 0.80, sensitivity 0.68 vs. 0.65, specificity 0.82 vs. 0.78). CONCLUSIONS: LV shape parameters derived from gated SPECT MPI have the promise to improve the prediction of the super-response to CRT. Moreover, ESE provides incremental value over existing clinical and nuclear imaging variables.

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.

Posttraumatic Stress Disorder, Myocardial Perfusion, and Myocardial Blood Flow: A Longitudinal Twin Study.

BACKGROUND: The link between posttraumatic stress disorder (PTSD) and ischemic heart disease remains elusive owing to a shortage of longitudinal studies with a clinical diagnosis of PTSD and objective measures of cardiac compromise. METHODS: We performed positron emission tomography in 275 twins who participated in two examinations approximately 12 years apart. At both visits, we obtained a clinical diagnosis of PTSD, which was classified as long-standing (both visit 1 and visit 2), late onset (only visit 2), and no PTSD (no PTSD at both visits). With positron emission tomography, we assessed myocardial flow reserve (MFR), which, in absence of significant coronary stenoses, indexes coronary microvascular function. We compared positron emission tomography data at visit 2 across the three categories of longitudinally assessed PTSD and examined changes between the two visits. RESULTS: Overall, 80% of the twins had no or minimal obstructive coronary disease. Yet, MFR was depressed in twins with PTSD and was progressively lower across groups with no PTSD (2.13), late-onset PTSD (1.97), and long-standing PTSD (1.93) (p = .01). A low MFR (a ratio <2.0) was present in 40% of the twins without PTSD, in 56% of those with late-onset PTSD, and in 72% of those with long-standing PTSD (p < .001). Associations persisted in multivariable analysis, when examining changes in MFR between visit 1 and visit 2, and within twin pairs. Results were similar by zygosity. CONCLUSIONS: Longitudinally, PTSD is associated with reduced coronary microcirculatory function and greater deterioration over time. The association is especially noted among twins with chronic, long-standing PTSD and is not confounded by shared environmental or genetic factors.