13N-ammonia Positron Emission Tomography Research Articles

Effect of acute intravenous beta-blocker administration on myocardial blood flow during same-day hybrid CCTA/PET imaging.

This study aimed to evaluate the impact of acute intravenous beta-blocker administration on myocardial blood flow (MBF) during same-day hybrid coronary computed tomography angiography (CCTA) and 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI). Previous research on the discontinuation of oral beta-blockers before MPI has shown mixed results, with no studies yet exploring the acute intravenous administration in the context of same-day hybrid imaging. This retrospective study included patients with suspected chronic coronary syndromes undergoing same-day hybrid CCTA/13N-ammonia PET MPI. Exclusion criteria comprised coronary artery stenosis ≥ 50% or regional perfusion abnormalities on PET, and baseline oral beta-blocker medication. Intravenous metoprolol (up to 30mg) was administered as needed for heart rate control before CCTA. MBF measurements were obtained at rest (rMBF) and during stress (sMBF), and myocardial flow reserve (MFR) was calculated. After excluding 281 patients, 154 were eligible for propensity-score matching, resulting in 108 patients divided into two equal groups based on beta-blocker administration. The groups showed no significant differences in baseline characteristics. Among those who received beta-blockers, there was a significant decrease in sMBF (2.21 [IQR 1.72-2.78] versus 2.46 [2.08-2.99] ml∙min-1∙g-1, p = 0.027) and MFR (3.46 [2.70-4.05] versus 3.79 [3.22-4.46], p = 0.030), respectively, compared to those who did not receive beta-blockers. In contrast, rMBF remained unaffected (0.65 [0.54-0.78] versus 0.64 [0.55-0.76] ml∙min-1∙g-1, p = 0.931). Acute intravenous beta-blocker administration significantly impacts MBF, leading to a slight reduction in sMBF and MFR. In contrast, rMBF appears unaffected, suggesting that beta-blockers primarily affect the coronary capacity to respond to vasodilators.

Hemodynamic Evaluation of Coronary Artery Lesions after Kawasaki Disease: Comparison of Fractional Flow Reserve during Cardiac Catheterization with Myocardial Flow Reserve during 13N-Ammonia PET

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial flow reserve (MFR), and myocardial blood flow volume fraction (MBF) and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 men, 1 woman) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86 ± 0.13 vs. 1.08 ± 0.09, p = 0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23 ± 0.23 vs. 1.88 ± 0.29, p = 0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

Risk Stratification Using Right Ventricular Longitudinal Strain Ratio Derived from 13N-Ammonia PET in Patients with Ischemic Heart Disease.

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia (13N-NH3) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13N-NH3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.

Duration of adenosine-induced myocardial hyperemia - Insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging.

To assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared to a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects. Quantitative MBF at rest (rMBF), during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET-MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 minutes between adenosine infusion offset and rest-imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group (0.80 [IQR 0.66-1.00] vs. 0.70 [0.58-0.83] ml·min-1·g-1, p < 0.001) and, as sMBF was identical between groups (2.52 [2.20-2.96] vs. 2.50 [1.96-3.11], p = 0.347), MFR was significantly lower in the stress-rest group (3.07 [2.43-3.88] vs. 3.50 [2.63-4.10], p < 0.001). There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, p = 0.002) and between Δtstress-rest and MFR (r = 0.163, p = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest. Intravenously applied adenosine induces a long-lasting hyperemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR.

The impact of predictability of coronary flow reserve for non-cardiovascular mortality, all-cause mortality, cardiovascular mortality in dialysis population

Abstract Background In the clinical setting, ischemic heart disease (IHD) is a major problem not only in general patients but also in regular hemodialysis (HD) patients. 13N-ammonia positron emission tomography (13NH3PET) is an established and excellent diagnostic test for IHD. We have reported about the predictability of coronary flow reserve (CFR) in poor prognosis in HD population. Some prior studies show that low CFR predicts poor prognosis for not only cardiovascular event but also all-cause mortality. Although it is well-known that CFR is an important predictor, there are limited data about predictability of CFR for non-cardiovascular (non-CV) mortality. We investigated the prognostic predictability of all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Methods In total 1020, patients who underwent NH3+PET suspected of ischemic heart disease from May 2013 to May 2022 were included. They are divided into two groups according to CFR cut off value (CFR=2.0). 465 patients were included into low CFR group and 555 patients were included into high CFR group. We collected all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. CV mortality was defined death from myocardial infarction, sudden death, stroke, heart failure, arrhythmia and ischemic colitis. We have followed them in 1282 days (median, 1st-3rd quartile was 510-2116). Results We found any cause death were 285 cases (the high CFR group vs the low CFR group; 165 (35.5%) vs 118 (21.3%), p&amp;lt;0.001), CV death were 121 cases (52 (9.4%) vs 68 (14.6%), p=0.010) and non-CV death were 164 cases (66(11.9%) vs 97 (20.9%, p&amp;lt;0.001)). Kaplan-Meier curve analysis and Cox regression model shows the low CFR groups shows poor prognosis for all-cause mortality (log rank; p&amp;lt;0.001, hazard ratio (HR); 1.9964, 95% confidential interval (CI); 1.576-2.529), CV mortality (log rank; p=0.0009, HR; 1.834, 95%CI; 1.278-2.633) and non-CV mortality (log rank; p&amp;lt;0.0001, HR; 2.213, 95%CI; 1.555-2.907). Furthermore, multivariate cox regression model shows the continuous value of CFR is an independent predictor for both all-cause mortality (HR0.180, 95%CI 0.074-0.435, p=0.0001) and non-CV mortality (HR0.553, 95% CI0.397-0.769, p=0.0004). Conclusion In dialysis population, CFR is an important predictor for all-cause mortality, CV mortality and non-CV mortality. In addition, CFR would predict non-CV death in HD population even though CFR is an index for IHD.

Reproducibility of Left Ventricular Function Derived From Cardiac Magnetic Resonance and Gated 13N-Ammonia Positron Emission Tomography Myocardial Perfusion Imaging: A Head-to-Head Comparison Using Hybrid Positron Emission Tomography/Magnetic Resonance

Cardiac magnetic resonance (CMR) and gated 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) offer accurate and highly comparable global left ventricular ejection fraction (LVEF) measurements. In addition to accuracy, however, reproducibility is crucial to avoid variations in LVEF assessment potentially negatively impacting treatment decisions. We performed a head-to-head comparison of the reproducibility of LVEF measurements derived from simultaneously acquired CMR and PET-MPI using different state-of-the-art commercially available software. 93 patients undergoing hybrid PET/MR were retrospectively included. LVEF was derived from CMR and PET-MPI at two separate core labs, using two state-of-the-art software packages for CMR (cvi42 and Medis Suite MR) and PET (QPET and CardIQ Physio). Intra- and inter-reader agreement was assessed using correlation and Bland-Altman (BA) analyses. While intra- and inter-reader reproducibility of LVEF was high among both modalities and all software packages (r≥0.87 and ICC≥0.91, all significant at p<0.0001), LVEF derived from PET-MPI and analyzed with QPET outperformed all other analyses (intra-reader reproducibility: r=0.99, ICC=0.99; inter-reader reproducibility: r=0.98, ICC=1.00; Pearson correlations significantly higher than all others at p≤0.0001). BA analyses showed smaller biases for LVEF derived from PET-MPI (-0.1% and +0.9% for intra-reader, -0.4% and -0.8% for inter-reader agreement) than those derived from CMR (+0.7% and +2.8% for intra-reader, -0.9% and -2.2% for inter-reader agreement) with similar results for BA limits of agreement. Gated 13N-ammonia PET-MPI provides equivalent reproducibility of LVEF compared to CMR. It may offer a valid alternative to CMR for patients requiring LV functional assessment.

Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes

BackgroundMyocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear. MethodOverall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5–10%); and Group III (n = 155), moderate-to-severe (> 10%). ResultsCardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48–5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37–8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59–2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR. ConclusionImpaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

13N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease

BackgroundIschemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. 13N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). MethodsOverall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET. ResultsPMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan–Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13–8.15; p < 0.0001). ConclusionsPMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.

Coronary artery bypass grafting transiently improves myocardial flow reserve in patients with impaired left ventricular function

BackgroundMyocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography is an index used to evaluate ischemic cardiomyopathy and predict the prognosis of patients with coronary artery disease (CAD). This study aimed to evaluate the short-term changes in MFR in patients who underwent coronary artery bypass grafting (CABG). In addition, as a reference, we showed the changes in MFR in the percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) patient groups. MethodsTo determine the short-term effects of CABG in CAD with left ventricular dysfunction, myocardial blood flow (MBF) and MFR were measured before and after CABG. Additionally, we showed changes in MBF and MFR of the PCI and OMT patient groups during treatment. ResultsWe observed that resting MBF did not significantly increase from baseline to post-CABG (0.84 ± 0.32 vs. 0.83 ± 0.23, P = 0.958); however, stress MBF increased significantly from baseline to post-CABG (1.23 ± 0.64 vs. 1.49 ± 0.42, P < 0.001). The global MFR increased significantly from baseline to post-CABG (1.49 ± 0.42 mL/g/min vs. 1.91 ± 0.51 mL/g/min, P < 0.001). Additionally, stress and resting ejection fraction (EF) significantly increased (stress EF: 42 ± 18.7% vs. 50.9 ± 18%, P = 0.005; resting EF: 45.8 ± 19.5% vs. 52.1 ± 19.4%, P = 0.031). ConclusionsThis study demonstrated that CABG significantly improved MFR in a short period of time with left ventricular dysfunction. These findings suggest that epicardial coronary artery patency restores myocardial microcirculatory dysfunction in the short term.

Radiomics for the detection of diffusely impaired myocardial perfusion: A proof-of-concept study using 13N-ammonia positron emission tomography

AimThe current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). MethodsData from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., < 2 and ≥ 2), as derived from quantitative PET analysis. We extracted radiomic features from retention images at each of five different gray-level (GL) discretization (8, 16, 32, 64, and 128 bins). Outcome independent and dependent feature selection and subsequent univariate and multivariate analyses was performed to identify image features predicting reduced global MFR. ResultsA total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. ConclusionA single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion—a descriptive PET/MR myocarditis study

PurposeWhether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis.MethodsFifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18).ResultsCompared to remote segments, healed segments showed higher stress MBF (2.71 mL*min−1*g−1 [IQR 2.18–3.08] vs. 2.20 mL*min−1*g−1 [1.75–2.68], p < 0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p < 0.0001), and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE.ConclusionIn patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.Graphical abstractCMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Impact of myocardial inflammation on quantitative myocardial perfusion at long-term follow-up - a descriptive hybrid PET/MR myocarditis study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF). Background Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. Objectives To assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. Methods Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n=469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n=118), and scarred (LGE at follow-up, n=72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n=18). Results Compared to remote segments, healed segments showed higher stress MBF (2.71mL*min-1*g-1 [IQR 2.18–3.08] vs. 2.20 mL*min-1*g-1 [1.75–2.68], p&amp;lt;0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p&amp;lt;0.0001) and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ∼30% (p&amp;lt;0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with myocardial scar but without corresponding LGE. Conclusions In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.

Coronary microvascular dysfunction detected by 13N-ammonia positron emission tomography in a patient with repaired aortic coarctation.

Coronary microvascular dysfunction detected by 13N-ammonia positron emission tomography in a patient with repaired aortic coarctation.

A simplified method to correct saturation of arterial input function for cardiac magnetic resonance first-pass perfusion imaging: validation with simultaneously acquired PET

BackgroundFirst-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on 13N-ammonia positron emission tomography (PET). MethodsSixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 mCi of 13N-ammonia. The MRI perfusion acquisition started simultaneously with the start of the PET acquisition after the injection of a 0.075 mmol/kg gadolinium contrast agent. Cardiac stress imaging was initiated after the administration of regadenoson 20 s prior to PET-MRI scanning. The saturation part of the MRI AIF data was modeled as a gamma variate curve, which was then estimated for a true AIF by minimizing a cost function according to various boundary conditions. A standard AHA 16-segment model was used for comparative analysis of absolute MBF from PET and MRI. ResultsOverall, there were 256 segments in 16 patients, mean resting perfusion for PET was 1.06 ± 0.34 ml/min/g and 1.04 ± 0.30 ml/min/g for MRI (P = 0.05), whereas mean stress perfusion for PET was 2.00 ± 0.74 ml/min/g and 2.12 ± 0.76 ml/min/g for MRI (P < 0.01). Linear regression analysis in MBF revealed strong correlation (r = 0.91, slope = 0.96, P < 0.001) between PET and MRI. Myocardial perfusion reserve, calculated from the ratio of stress MBF over resting MBF, also showed a strong correlation between MRI and PET measurements (r = 0.82, slope = 0.81, P < 0.001). ConclusionThe results demonstrated the feasibility of the simplified AIF estimation method for the accurate quantification of MBF by MRI with single sequence and single contrast injection. The MRI MBF correlated strongly with PET MBF obtained simultaneously. This post-processing technique will allow easy transformation of clinical perfusion imaging data into quantitative information.

Prediction of cardiovascular events using myocardial strain ratio derived from 13N-ammonia positron emission tomography.

Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH3-PET), can predict the prognosis of patients with various heart diseases. We aimed to investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR. Ninety-five patients underwent NH3-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI). The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (p = 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59-33.7, p = 0.011). MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD. • We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone. • MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease. • MSR is a potential new indicator of revascularization.

Prognostic Value of Simultaneous Analysis with Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13N-Ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in patients with coronary artery disease (CAD). Right ventricular global longitudinal strain (RVGLS) measured by magnetic resonance imaging (MRI) is used to evaluate RV function and predict cardiac events. This study aimed to evaluate the prognostic value of MFR and RVGLS measured by hybrid 13N-ammonia PET/MRI in patients with CAD.Sixty-one patients who underwent 13N-ammonia PET/MRI were analyzed. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. At a follow-up of 2.8 ± 1.9 years, 21 events had occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR < 1.80 than in that with MFR ≥ 1.80 (P < 0.001). Additionally, the event-free rate was significantly lower in the group with RVGLS > -18.22% than in that with RVGLS ≤ -18.22% (P = 0.025). After dividing the patients into 4 groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR < 1.80 and RVGLS > -18.22% than any other groups (P < 0.001). In a Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD.The simultaneous assessment of MFR and RVGLS by 13N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

Impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease

Objective: This study sought to investigate the impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease. Methods: We retrospectively analyzed clinical data of male patients diagnosed with suspected coronary microvascular dysfunction (CMD) in the First Hospital of Shanxi Medical University between December 2015 and August 2021. All patients underwent the one-day rest and stress 13N-ammonia positron emission tomography myocardial perfusion imaging. Overall obesity was defined by body mass index (BMI) ≥28 kg/m2 and abdominal obesity was defined by waist circumference ≥90 cm. Hyperemic myocardial blood flow (MBF)<2.3 ml·min-1·g-1 or coronary flow reserve (CFR)<2.5 were referred as CMD. All patients were grouped based on their BMI and waist circumference. MBF, CFR, the incidence of CMD, hemodynamic parameters, and cardiac function were compared among the groups. Results: A total of 136 patients were included. According to BMI and waist circumference, patients were categorized into 3 groups: control group (n=45), simple abdominal obesity group (n=53) and compound obesity group (n=38). Resting MBF did not differ between groups (F=0.02,P=0.994). Compared with the control group, hyperemic MBF was significantly lower in the simple abdominal obesity and compound obesity groups ((2.82±0.64) ml·min-1·g-1, (2.44±0.85) ml·min-1·g-1 and (2.49±0.71) ml·min-1·g-1, both P<0.05, respectively). Hyperemic MBF was comparable among the groups of patients with obesity (P=0.772). CFR was significantly lower in the simle abdominal obesity group compared with the control group (2.87±0.99 vs. 3.32±0.62,P=0.012). Compared with the control group, CFR tended to be lower in the compound obesity group (3.02±0.91 vs. 3.32±0.62,P=0.117). The incidence of CMD was significantly higher in both the simple abdominal obesity and compound obesity groups than in the control group (62.3%, 52.6% vs. 22.2%, both P<0.01, respectively). Waist circumference was an independent risk factor for male CMD (OR=1.057, 95%CI: 1.013-1.103, P=0.011). Conclusions: In male patients with non-obstructive coronary artery disease, abdominal obesity is associated with decreased coronary microvascular function. Male patients with simple abdominal obesity face the highest risk of CMD.

Association of resting left ventricular global longitudinal strain with myocardial perfusion abnormalities evaluated by 13 N-ammonia positron emission tomography in patients with stable angina pectoris and normal left ventricular ejection fraction.

Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13 N-ammonia positron emission tomography (13 N-NH3 -PET)-myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. We selected 157 patients with suspected stable angina pectoris who underwent both ATP-stress NH3 -PET-MPI and 2-dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0-3; n=101), Group M (mildly to moderately abnormal perfusion; SSS, 4-11; n=41), or Group S (severely abnormal perfusion; SSS, 12+; n=15). GLS was more impaired as myocardial perfusion abnormality severity increased (-17.9±2.9% for Group N, -16.8±3.1% for Group M, and -14.2±3.5% for Group S; p<.001). GLS was weakly but significantly correlated with SSS (R=.32, p<.001), summed difference score (R=.32, p<.001), and myocardial blood flow during stress (R=-0.27, p<.001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was .65, and the optimal cutoff value for GLS was -16.5%, with sensitivity and specificity of 59% and 66%, respectively. In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease.

Development and evaluation of a radiomics model of resting 13N-ammonia positron emission tomography myocardial perfusion imaging to predict coronary artery stenosis in patients with suspected coronary heart disease.

Coronary angiography (CAG) is usually performed in patients with coronary heart disease (CHD) to evaluate the coronary artery stenosis. However, patients with iodine allergy and renal dysfunction are not suitable for CAG. We try to develop a radiomics machine learning model based on rest 13N-ammonia (13N-NH3) positron emission tomography (PET) myocardial perfusion imaging (MPI) to predict coronary stenosis. Eighty-four patients were included with the inclusion criteria: adult patients; suspected CHD; resting MPI and CAG were performed; and complete data. Coronary artery stenosis >75% were considered to be significant stenosis. Patients were randomly divided into a training group and a testing group with a ratio of 1:1. Myocardial blood flow (MBF), perfusion defect extent (EXT), total perfusion deficit (TPD), and summed rest score (SRS) were obtained. Myocardial static images of the left ventricular (LV) coronary segments were segmented, and radiomics features were extracted. In the training set, the conventional parameter (MPI model) and radiomics (Rad model) models were constructed using the machine learning method and were combined to construct a nomogram. The models' performance was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, decision analysis curve (DCA), and calibration curves. Testing and subgroup analysis were performed. MPI model was composed of MBF and EXT, and Rad model was composed of 12 radiomics features. In the training set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.795/0.778/0.937/0.511, 0.912/0.825/0.760/0.936 and 0.911/0.865/0.924/0.766 respectively. In the testing set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.798/0.722/0.659/0.841, 0.887/0.810/0.744/0.932 and 0.900/0.849/0.854/0.841 respectively. The AUC of Rad model and nomogram were significantly higher than that of MPI model. The DCA curve also showed that the clinical net benefit of the Rad model and nomogram was similar but greater than that of MPI model. The calibration curve showed good agreement between the observed and predicted values of the Rad model. In the subgroup analysis of Rad model, there was no significant difference in AUC between subgroups. The Rad model is more accurate than the MPI model in predicting coronary stenosis. This noninvasive technique could help improve risk stratification and had good generalization ability.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events

BackgroundCardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. ObjectivesThis analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. MethodsA total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. ResultsIn total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. ConclusionsAbnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.