Diagnostic Performance of Quantitative Perfusion Cardiac Magnetic Resonance Imaging in Patients with Prior Coronary Artery Disease.

AIMS: The diagnostic performance of quantitative perfusion cardiac magnetic resonance (QP-CMR) imaging has scarcely been evaluated in patients with a history of coronary artery disease (CAD) and new onset chest pain. The present study compared the diagnostic performance of automated QP-CMR for detection of fractional flow reserve (FFR) defined hemodynamically significant CAD with visual assessment of first-pass stress perfusion CMR (v-CMR) and quantitative [15O]H2O positron emission tomography (PET) imaging in a true head-to-head fashion in patients with prior CAD. METHODS AND RESULTS: This PACIFIC-2 substudy included 145 symptomatic chronic coronary symptom patients with prior myocardial infarction (MI) and/or percutaneous coronary intervention (PCI). All patients underwent dual-sequence, single bolus perfusion CMR and [15O]H2O PET perfusion imaging followed by invasive coronary angiography with three-vessel FFR. Hemodynamically significant CAD was defined as an FFR ≤0.80. QP-CMR, v-CMR and PET exhibited a sensitivity of 66%, 67%, and 80%, respectively, whereas specificity was 60%, 62%, and 63%. Sensitivity of QP-CMR was lower than PET (P=0.015), whereas specificity of QP-CMR and PET was comparable. Diagnostic accuracy and area under the curve (AUC) of QP-CMR (64% and 0.66) was comparable to both v-CMR (66% [P=NS] and 0.67 (P=NS]) and PET (74% [P=NS] and 0.78 [P=NS]). CONCLUSIONS: In patients with prior MI and/or PCI, the diagnostic performance of QP-CMR was comparable to visual assessment of first-pass stress perfusion CMR and quantitative [15O]H2O PET for the detection of hemodynamically significant CAD as defined by FFR.

Performance of simplified methods for quantification of [18F]NaF uptake in fibrodysplasia ossificans progressiva.

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. 18F-fluoride uptake in newly formed bone can be evaluated using [18F]NaF (i.e., sodiumfluoride) PET/CT, identifying active areas of bone formation in FOP. The purpose of this study was to assess the performance of various semi-quantitative methods with full kinetic analysis. Results: Seven patients (age range: 20-31 years) with FOP underwent dynamic [18F]NaF scans at baseline and after one year. [18F]NaF uptake was measured in aorta descendens, vertebrae, heterotopic bone lesions and metabolically active regions on PET, and quantified using nonlinear regression (NLR) analysis together with standardized uptake value (SUV) and target-to-blood ratio (TBR). SUV was on measured the 40-45 min frame of the dynamic sequence (SUV40-45) and on the subsequent static sweep (SUVStatic). Correlations between and SUV40-45 and NLR-derived Ki were comparable when normalized to body weight (r = 0.81, 95% CI 0.64-0.90), lean body mass (r = 0.79, 95% CI 0.61-0.89) and body surface area (r = 0.84, 95% CI 0.70-0.92). Correlation between TBR40-45 and NLR-derived Ki (r = 0.92, 95% CI 0.85-0.96) was higher than for SUV40-45. Correlation between TBR40-45 and NLR-derived Ki was similar at baseline and after one year (r = 0.93 and 0.94). The change in TBR40-45 between baseline measurement and after one year correlated best with the change in NLR-derived Ki in the PET-active lesions (r = 0.87). Conclusion: The present data supports the use of TBR for assessing fluoride uptake in PET-active lesions in FOP. Clinical trial registration: Sub-study of the Lumina-1 trial (clinicaltrials.gov, NCT03188666, registered 13-06-2017).

Eagle syndrome: tissue characteristics and structure of the styloid process.

Eagle syndrome is a bone disease where elongation of the styloid process leads to throat and neck pain, and in severe cases neurovascular symptoms such as syncope and neuralgia. The pathophysiology of Eagle syndrome is poorly understood with various theories having been proposed how this elongation is caused. To better understand the pathophysiology, we performed a work-up in 6 patients presenting with Eagle syndrome. Patients mainly presented with pain on turning the neck (100%), foreign body sensation (67%), tension in the neck (67%), and dysphagia (50%). The typical length of the styloid process ranges from 25 to 30 mm; however, [18F]NaF (sodium fluoride) PET/CT showed elongated styloid processes with an average length of 52.1 ± 15.6 mm (mean ± SD) with increased turnover at the base of one of the styloid processes. The removed styloid processes were further examined by histology, micro-CT, quantitative backscatter electron imaging (qBEI), Fourier transform infrared spectroscopy (FTIR), and circularly polarized light imaging. Histology revealed one case of a fractured styloid process healing through callus formation and one case of pseudarthrosis. Bone mineral density and mineralization was similar in the styloid processes when compared to cortical bone samples derived from the mandibular bone of different patients. Circular polarized light microscopy showed a collagen orientation in the styloid process comparable to the cortical bone samples with a distinct separation of collagen structure between the mineralized structure and the surrounding soft tissue with FTIR analysis demonstrating a typical composition of bone. This altogether suggests that the elongated styloid processes in Eagle syndrome are mature bone, capable of endochondral repair, possibly growing from the base of the process through endochondral ossification, rather than being a form of secondary calcification of the stylohyoid ligament as previously postulated.

The effect of hydrostatic pressure on invasive coronary pressure measurements: Comparison with [15O]H2O-positron emission tomography flow data.

BACKGROUND: Fractional flow reserve (FFR) has emerged as the invasive gold standard for assessing vessel-specific ischemia. However, FFR measurements are influenced by the hydrostatic effect, which might adversely impact the assessment of ischemia. AIMS: This study aimed to investigate the impact of hydrostatic pressure on FFR measurements by correcting for the height and comparing FFR with [15O]H2O positron emission tomography (PET)-derived relative flow reserve (RFR). METHODS: The 206 patients were included in this analysis. Patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive coronary angiography with routine FFR in every epicardial artery. Height differences between the aortic guiding catheter and distal pressure sensor were quantified on CCTA images. An FFR ≤ 0.80 was considered significant. RESULTS: The study found a reclassification in 7% of the coronary arteries. Notably, 11% of left anterior descending (LAD) arteries were reclassified from hemodynamically significant to nonsignificant. Conversely, 6% of left circumflex (Cx) arteries were reclassified from nonsignificant to significant. After correcting for the hydrostatic pressure effect, the correlation between FFR and PET-derived RFR increased significantly from r = 0.720 to r = 0.786 (p = 0.009). The average magnitude of correction was +0.05 FFR units in the LAD, -0.03 in the Cx, and -0.02 in the right coronary artery. CONCLUSION: Hydrostatic pressure has a small but clinically relevant influence on FFR measurements obtained with a pressure wire. Correcting for this hydrostatic error significantly enhances the correlation between FFR and PET-derived RFR.

Diagnostic accuracy of non-invasive cardiac imaging modalities in patients with a history of coronary artery disease: a meta-analysis.

BACKGROUND: The diagnostic performance of non-invasive imaging techniques for detecting obstructive coronary artery disease (CAD) in patients with a history of myocardial infarction or percutaneous coronary intervention has not been comprehensively evaluated. This meta-analysis assesses the diagnostic value of coronary CT angiography (CCTA), CCTA combined with CT perfusion (CCTA+CTP), cardiac MRI (CMR) and single-photon emission CT (SPECT) compared with invasive reference standards. METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from 2005 to September 2022 for prospective, blinded studies including populations with ≥50% prior CAD. RESULTS: We identified 18 studies encompassing 3265 patients, with obstructive CAD present in 64%. The per-patient sensitivity of CCTA (0.95; 95% CI 0.92 to 0.98), CCTA+CTP (0.93; 95% CI 0.84 to 0.98) and CMR (0.91; 95% CI 0.86 to 0.94) was high, while SPECT showed lower sensitivity (0.63; 95% CI 0.52 to 0.73). SPECT had higher specificity compared with CCTA (0.66; 95% CI 0.56 to 0.76 vs 0.37; 95% CI 0.29 to 0.46), but was comparable to CCTA+CTP (0.59; 95% CI 0.49 to 0.69) and CMR (0.69; 95% CI 0.53 to 0.81). The area under the curve for SPECT was the lowest (0.70; 95% CI 0.58 to 0.87), while CCTA (0.91; 95% CI 0.86 to 0.98), CCTA+CTP (0.89; 95% CI 0.73 to 1.00) and CMR (0.91; 95% CI 0.80 to 1.00) showed similar high values. CONCLUSIONS: In patients with prior CAD, CCTA, CCTA+CTP and CMR demonstrated high diagnostic performance, whereas SPECT had lower sensitivity. These findings can guide the selection of non-invasive imaging techniques in this high-risk population. PROSPERO REGISTRATION NUMBER: CRD42022322348.

Location-Specific Prognostic Significance of Plaque Burden, Stenosis, and Plaque Morphology in Coronary Artery Disease.

AIMS: To investigate the location-specific prognostic significance of plaque burden, diameter stenosis and plaque morphology. METHODS AND RESULTS: Patients without a documented cardiac history who underwent coronary computed tomography angiography (CCTA) for suspected coronary artery disease were included. Percentage atheroma volume (PAV), maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. When adjusted for traditional risk factors and presence of PAV on other locations, only proximal PAV was independently associated with MACE. However, PAV of the proximal segments was strongly correlated to PAV localized at the mid (R= 0.76) and distal segments (R=0.74, p<0.01 for both). When only adjusted for cardiovascular risk factors, the area under the curve (AUC) to predict MACE for proximal PAV was 0.73 (95%CI 0.69-0.76), which was similar compared to mid PAV (AUC 0.72, 95%CI 0.68-0.76) and distal PAV (AUC 0.72, 95%CI 0.68-0.76). Similar results were obtained using diameter stenosis instead of PAV. The presence of proximal low-attenuation plaque had borderline additional prognostic value. CONCLUSIONS: Proximal PAV was the strongest predictor of MACE when adjusted for cardiovascular risk factors and plaque at other locations. However, when presence of plaque was only adjusted for cardiovascular risk factors, proximal, mid, and distal plaque localization showed a similar predictive ability for MACE.

PET myocardial perfusion imaging: Trends, challenges, and opportunities.

Various non-invasive images are used in clinical practice for the diagnosis and prognostication of chronic coronary syndromes. Notably, quantitative myocardial perfusion imaging (MPI) through positron emission tomography (PET) has seen significant technical advancements and a substantial increase in its use over the past two decades. This progress has generated an unprecedented wealth of clinical information, which, when properly applied, can diagnose and fine-tune the management of patients with different types of ischemic syndromes. This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and revascularization clinical trials, along with future perspectives.

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study.

BACKGROUND AND AIMS: Microvascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). METHODS: In this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. RESULTS: Among 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). CONCLUSIONS: Our study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

Determining Hemodynamically Significant Coronary Artery Disease: Patient-Specific Cutoffs in Quantitative Myocardial Blood Flow Using [15O]H2O PET Imaging.

Currently, cutoffs of quantitative [15O]H2O PET to detect fractional flow reserve (FFR)-defined coronary artery disease (CAD) were derived from a single cohort that included patients without prior CAD. However, prior CAD, sex, and age can influence myocardial blood flow (MBF). Therefore, the present study determined the influence of prior CAD, sex, and age on optimal cutoffs of hyperemic MBF (hMBF) and coronary flow reserve (CFR) and evaluated whether cutoff optimization enhanced diagnostic performance of quantitative [15O]H2O PET against an FFR reference standard. Methods: Patients with chronic coronary symptoms underwent [15O]H2O PET and invasive coronary angiography with FFR. Optimal cutoffs for patients with and without prior CAD and subpopulations based on sex and age were determined. Results: This multicenter study included 560 patients. Optimal cutoffs were similar for patients with (n = 186) and without prior CAD (hMBF, 2.3 vs. 2.3 mL·min-1·g-1; CFR, 2.7 vs. 2.6). Females (n = 190) had higher hMBF cutoffs than males (2.8 vs. 2.3 mL·min-1·g-1), whereas CFRs were comparable (2.6 vs. 2.7). However, female sex-specific hMBF cutoff implementation decreased diagnostic accuracy as compared with the cutoff of 2.3 mL·min-1·g-1 (72% vs. 82%, P < 0.001). Patients aged more than 70 y (n = 79) had lower hMBF (1.7 mL·min-1·g-1) and CFR (2.3) cutoffs than did patients aged 50 y or less, 51-60 y, and 61-70 y (hMBF, 2.3-2.4 mL·min-1·g-1; CFR, 2.7). Age-specific cutoffs in patients aged more than 70 y yielded comparable accuracy to the previously established cutoffs (hMBF, 72% vs. 76%, P = 0.664; CFR, 80% vs. 75%, P = 0.289). Conclusion: Patients with and without prior CAD had similar [15O]H2O PET cutoffs for detecting FFR-defined significant CAD. Stratifying patients according to sex and age led to different optimal cutoffs; however, these values did not translate into an increased overall accuracy as compared with previously established thresholds for MBF.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Hemodynamic Insights into Combined Fractional Flow Reserve and Instantaneous Wave-Free Ratio Assessment Through Quantitative [15O]H2O PET Myocardial Perfusion Imaging.

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [15O]H2O PET-derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [15O]H2O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low (n = 79), FFR high/iFR low (n = 22), FFR low/iFR high (n = 22), and FFR high/iFR high (n = 345). Predefined [15O]H2O PET thresholds for ischemia were 2.3 mL·min-1·g-1 or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min-1·g-1), FFR high/iFR low (2.41 ± 0.80 mL·min-1·g-1), and FFR low/iFR high (2.40 ± 0.69 mL·min-1·g-1) groups compared with the concordant high group (2.91 ± 0.84 mL·min-1·g-1) (P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR (P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26-0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [15O]H2O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity.

Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .

Prognostic Value of Modified Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging.

BACKGROUND: Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [15O]H2O positron emission tomography perfusion imaging. METHODS: Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction. RESULTS: During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P<0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P<0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P<0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P=0.017). CONCLUSIONS: [15O]H2O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [15O]H2O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization.

PURPOSE: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue. METHODS: Symptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement. RESULTS: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase. CONCLUSIONS: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

The diagnostic performance of quantitative flow ratio and perfusion imaging in patients with prior coronary artery disease.

AIMS: In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)]. METHODS AND RESULTS: This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion. Patients underwent SPECT, PET, and CMR followed by invasive coronary angiography with fractional flow reserve (FFR) measurements of all major coronary arteries (N = 567), except for vessels with a sub-total or chronic total occlusion. Quantitative flow ratio computation was attempted in 488 (86%) vessels with measured FFR available (FFR ≤0.80 defined haemodynamically significant CAD). Quantitative flow ratio analysis was successful in 334 (68%) vessels among 166 patients and demonstrated a higher accuracy (84%) and sensitivity (72%) compared with SPECT (66%, P < 0.001 and 46%, P = 0.001), PET (65%, P < 0.001 and 58%, P = 0.032), and CMR (72%, P < 0.001 and 33%, P < 0.001). The specificity of QFR (87%) was similar to that of CMR (83%, P = 0.123) but higher than that of SPECT (71%, P < 0.001) and PET (67%, P < 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P < 0.001), PET (0.66, P < 0.001), and CMR (0.60, P < 0.001). CONCLUSION: QFR correlated better with FFR in patients with prior CAD than MPI, as reflected in the higher diagnostic performance measures for detecting FFR-defined, vessel-specific, significant CAD.

Characterizing the Bone Marrow Environment in Advanced-Stage Myelofibrosis during Ruxolitinib Treatment Using PET/CT and MRI: A Pilot Study.

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Warranty period of coronary computed tomography angiography and [15O]H2O positron emission tomography in symptomatic patients.

AIMS: Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET. METHOD AND RESULTS: Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year). CONCLUSION: As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD.

Comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT acquired in clinical practice for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome.

PURPOSE: Two commonly used imaging techniques to aid in the diagnosis of neurodegenerative parkinsonian syndromes are dopamine transporter (DAT) imaging with [123I]-FP-CIT single-photon emission computed tomography (DAT-SPECT) and positron emission tomography with [18F]-FDOPA (FDOPA-PET). This paper provides a unique series of parkinsonian patients who received both FDOPA-PET and DAT-SPECT in routine clinical practice and compares the reported results to assess potential differences between these two imaging techniques. METHODS: We present 11 patients with a clinically uncertain parkinsonian syndrome (CUPS), who received both FDOPA-PET and DAT-SPECT. All patients received an FDOPA-PET scan and DAT-SPECT as part of routine clinical care. RESULTS: The median time between the F-DOPA-PET scan and DAT-SPECT scan was 6 months (range 0-15 months). There was a discrepancy in the reported results of the FDOPA-PET and DAT-SPECT scans in nine patients, including 7 patients whose FDOPA-PET scan was reportedly normal, whereas their DAT-SPECT scan was abnormal. CONCLUSIONS: In this case series of CUPS patients, DAT-SPECT was more often rated as abnormal than FDOPA-PET. The striatal loss of FDOPA uptake can be less pronounced than that of DAT binding in CUPS patients in early disease stages. Consequently, the interpretation of FDOPA-PET scans in CUPS can sometimes be challenging in routine practice.