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Aims Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. Methods and results A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories: myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and −0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1–3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19–0.98, P = 0.04). Conclusion Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.

BackgroundFibrodysplasia ossificans progressiva (FOP), an ultra-rare disorder caused by mutations in the gene encoding activin A receptor type 1 (ACVR1), is characterized by painful flare-ups and cumulative heterotopic ossification (HO). Garetosmab, a fully-human monoclonal antibody blocking activin A, prevents HO in FOP mice.MethodsLUMINA-1 (NCT03188666) was a phase 2, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and effects on HO of intravenous (IV) garetosmab 10 mg/kg every 4 weeks (Q4W). Adult patients with FOP were randomized to garetosmab or placebo for 28 weeks (Period_1), followed by an open-label period (Period_2). After Period_2, patients were allowed to stay on garetosmab in an open-label extension. For Period_1, primary endpoints were HO total lesion activity (HO-TLA) by18F-sodium fluoride positron emission tomography (18F-NaF PET) and HO total lesion volume by computed tomography (CT). The Period_2 primary endpoint compared the number of new lesions in Period_2 versus Period_1. The safety primary endpoint was incidence and severity of TEAEs through the end of the Period 1 at week 28.FindingsPatients (n=44) were randomized to garetosmab (n=20) or placebo (n=24). In Period_1, there was a trend for garetosmab to decrease HO-TLA versus placebo (24.6%;P=0.07), primarily driven by near complete prevention of new lesions (97% decrease by18F-NaF PET, post-hocP=0.009; 90% relative reduction by CT, post-hocP=0.017); flare-ups were significantly reduced (P=0.0005). For placebo patients transitioning to garetosmab in Period_2, no patients developed new HO lesions (0% in Period_2 versus 40.9% in Period_1;P=0.0027) by CT. All 44 patients met primary safety endpoint of at least one TEAE during Period 1. Garetosmab was associated with more adverse events than placebo: mild recurrent epistaxis, madarosis, and skin/soft tissue infections. Overall, the AEs were predominantly mild in severity, with no effect on patients’ ability to receive garetosmab. Five deaths (5/44; 11.4%) occurred either in Period_2 or the open-label extension. The deaths were associated with baseline disease severity in some, preexisting comorbidities in others and occurred following 8-16 doses (median: 15) of garetosmab in the open label/follow-up periods.InterpretationGaretosmab reduced flare-ups and prevented new HO lesions in FOP patients. Although side effects were mild to moderate, there were a relatively high number of deaths for a small study; the deaths were not related to epistaxis and considered unlikely to be related to garetosmab.FundingRegeneron Pharmaceuticals, Inc.

AimsData 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 resultsPatients 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).ConclusionAs 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.

Objectives: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. Background: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). Methods: A total of 539 patients who underwent CCTA and [ 15O]H 2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. Results: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm 3, CPV >110 mm 3, NCPV >85 mm 3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). Conclusions: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

AIMS: The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p

Purpose To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. Results CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P r = 0.36; P 15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR. Conclusion CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

Contains fulltext : 229194.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)-derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices. BACKGROUND: Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR. METHODS: Of 120 patients (62% men, age 58.3 +/- 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements. RESULTS: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to >/=70% stenosis (-0.10, p < 0.001 and -0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (-0.10, p < 0.001 and -0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR. CONCLUSIONS: CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

BackgroundDiagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy results. However, these biopsies have several limitations, such as the risk of sampling error. Also, the prognostic impact of BM abnormalities is largely unclear. Although not currently used in clinical practice, imaging techniques might offer additional information. In this review, we investigated the value of BM, liver, and spleen imaging for diagnosis, prognostication, and response monitoring of the JAK2/CALR/MPL mutation-related MPNs (i.e. essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)).MethodsA systematic literature search was performed via PubMed, Embase and the Cochrane Library up to 2020 March 26th. Of 5505 identified records, 55 publications met the eligibility criteria (i.e. containing original data on the imaging appearance of BM, spleen, or liver in adult ET, PV, or MF patients, published in a peer-reviewed journal, written in English).ResultsMany explorative studies described imaging features, sometimes with comparisons to clinical characteristics. Studies reporting measures of diagnostic accuracy included 1) splenic transient elastography to predict BM fibrosis grade in MF, 2) dynamic contrast-enhanced MRI to discern MF patients from ET patients and healthy controls, and 3) 18-fluorodeoxyglucose PET to detect residual disease after stem cell transplantation in MF. The diagnostic accuracies of radiography and99mTc-colloid scintigraphy were derived from several other articles. Except for the study on 18-fluorodeoxyglucose PET, we established substantial concerns regarding risk of bias and applicability across these studies, using the QUADAS-2 tool. Three publications described a correlation between imaging results and prognosis, of which one quantified the effect.ConclusionsBased on current data, MRI (T1-weighted/STIR, Dixon) seems especially promising for the evaluation of BM fat content - and indirectly cellularity/fibrosis - in MF, and possibly for estimating BM cellularity in ET/PV. 18-fluorodeoxyglucose and 18-fluorothymidine PET/CT might be useful for evaluating BM fibrosis, with good reported accuracy of the former for the diagnosis of residual disease. Further research on these and other techniques is warranted to determine their exact value. Future researchers should improve methodology and focus on evaluation of diagnostic accuracy and prognostic implications of results.

Introduction: Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. This study evaluated the impact of CTO percutaneous coronary intervention (PCI) on absolute perfusion in remote myocardium. Methods: A total of 164 patients underwent serial [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging at baseline and 3 months after successful CTO PCI to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium subtended by non-target collateral donor coronary arteries. Results: Absolute perfusion indices in the CTO and remote myocardium showed a positive linear correlation before (hMBF: r=0.75, p-1 ·g -1 , p Conclusions: Baseline and post-PCI perfusion indices in remote and CTO myocardium were positively correlated. An overall increase in remote myocardial perfusion was observed following CTO PCI and the absolute perfusion increase in the CTO territory was an independent predictor of remote myocardial perfusion improvement. Successful CTO PCI impacts coronary hemodynamics in the closely interlinked CTO and remote myocardium.

Aims The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI). Methods and results In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P = 0.03) and MRI (64%, 57–72%, P = 0.052). Using FFR Conclusion In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.

Aims Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. Methods and results A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P Conclusion A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Fibrodysplasia Ossificans Progressiva (FOP) is a genetic disease characterized by the formation of heterotopic ossification (HO) in connective tissues. HO first develops in the thoracic region, before more peripheral sites are affected. Due to HO along the thoracic cage, its movements are restricted and pulmonary function deteriorates. Because development of HO is progressive, it is likely that pulmonary function deteriorates over time, but longitudinal data on pulmonary function in FOP are missing. Longitudinal pulmonary function tests (PFTs) from seven FOP patients were evaluated retrospectively to assess whether there were changes in pulmonary function during aging. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), residual volume (RV) and diffusing lung capacity for carbon dioxide divided by alveolar volume (DLCO/VA) were included. In addition, HO volume along the thorax together with its progression as identified by whole body low dose CT scans were correlated to PFT data. Per patient, aged 7–57 years at the time of the first PFT, three to nine PFTs were available over a period of 6–18 years. Restrictive pulmonary function, identified by TLC or suspected by FVC, was found in all, but one, patients. In three patients, TLC, FVC or both decreased further during the follow-up period. All, but one, patients had an increased RV. The DLCO/VA ratio was normal in all FOP patients. Interestingly, FEV1 increased after a surgical intervention to unlock the jaw. In four out of five patients total HO volume in the thoracic region progressed beyond early adulthood, but no further decline in FVC was observed. In conclusion, restrictive pulmonary function was found in the majority of patients already at an early age. Our data suggest that the deterioration in pulmonary function is age dependent.

The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [18F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [18F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP.A total of thirteen [18F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUVpeak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained.Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [18F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm3), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [18F]NaF uptake, with SUVpeak ranging from 8.4 to 17.9.In conclusion, HO may progress without signs of a flare-up. [18F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.

Contains fulltext : 209423.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [(15)O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow

Background: Risk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA). Methods: Patients with suspected CAD (n = 203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers. Findings: A total of 196 patients with analyzable protein levels (n = 332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79 ± 0·01, outperforming prediction with generally available clinical characteristics (AUC = 0·65 ± 0·04, p < 0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC = 0·85 ± 0·05), again outperforming prediction with generally available characteristics (AUC = 0·70 ± 0·04, p < 0·05). Interpretation: Using machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. Fund: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. Background: The clinical benefit of CTO PCI is questioned. Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [ 15O]H 2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min −1 · g −1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus −1 · g −1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min −1 · g −1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min −1 · g −1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Funding Acknowledgements Type of funding sources: None. Background. The value of serial coronary artery calcium (CAC) scores to predict changes in absolute myocardial perfusion and epicardial vasomotor function is poorly documented. Purpose. This study explored the association between progression of CAC score and changes in absolute myocardial perfusion. Methods. Fifty-three patients with single-vessel coronary artery disease (CAD) underwent [15O]H2O Positron Emission Tomography/Computed Tomography at 1 month (baseline), 1 year, and 3 years after percutaneous coronary intervention (PCI) to assess CAC scores, hyperemic myocardial blood flow (hMBF), coronary flow reserve (CFR) and cold pressor test MBF (CPT-MBF), within the context of the VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion) trial. Relationships between baseline CAC score and evolution of perfusion indices were explored with a mixed model-analysis. Results. Baseline CAC score was 0 in 9%, 0.1-99.9 in 40%, 100-399.9 in 36% and ≥400 in 15% of patients, respectively. In higher baseline CAC groups, scores increased more over time (overall p Conclusions. Higher baseline CAC was associated with lower hMBF and CFR. However, both baseline CAC and its progression were not associated with evolution of absolute hMBF, CFR and CPT-MBF over time, suggesting that CAC score and progression of CAC are poor indicators of change in absolute myocardial perfusion.

Funding Acknowledgements Type of funding sources: None. Background Inflammation is a key component in the atherosclerotic process, initiating and sustaining plaques and serving as a trigger for plaque rupture leading to myocardial infarction. Coronary computed tomography angiography (CCTA) derived pericoronary adipose tissue attenuation (PCATa) has been proposed as surrogate marker for coronary inflammation and might improve risk assessment on top of CCTA derived cardiovascular risk-factors: atherosclerotic burden and plaque vulnerability. Purpose To assess the prognostic value of PCATa beyond atherosclerotic burden and high-risk plaques (HRPs). Methods A total of 543 patients who underwent CCTA because of suspected CAD were included. CCTA assessment comprised coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and HRPs, total plaque volume (TPV), non-calcified plaque volume (NCPV), and PCATa. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Prognostic thresholds were determined for quantitative CCTA variables. Results During a median follow-up of 6.6 [interquartile range: 4.7-7.8] years, the endpoint was observed in 42 (20 MI/22 death) patients. CACS >83, obstructive CAD, HRPs, TPV >269mm3, and NCPV >83mm3 were associated with shorter time to the endpoint with unadujsted hazard ratio’s (HR) of 5.37 (95% confidence interval (CI): 2.56-11.29), 5.70 (95% CI: 2.40-13.55), 3.31 (95% CI: 1.80-6.07), 7.76 (95% CI: 3.59-16.81), and 6.77 (95% CI: 3.24-14.16), respectively (p -74.4 Hounsfield units was associated with worse prognosis (unadjusted HR: 1.99, 95% CI: 1.04-3.79, p = 0.037), whereas PCATa of the LAD and Cx were not associated with prognosis. PCATa of the RCA remained a significant predictor of death and non-fatal MI corrected for CCTA variables and clincal chacteristics associated with the endpoint (adjusted HR: 2.11, 95% CI: 1.11-4.04, p = 0.024). Conclusion Coronary inflammation determined by PCATa of the RCA provides incremental prognostic value beyond clinical characteristics and comprehensive CCTA assessment. Abstract Figure. Take-home figure

Background Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) leads to major reductions in ischemic burden. However, to date, studies investigating if more ischemia reduction after CTO PCI translates into an improved patient prognosis, are lacking. Purpose To evaluate if change in absolute myocardial perfusion after CTO PCI is related to patient prognosis. Methods Between 2013–2019, 219 prospectively recruited patients with a CTO underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and 3 months after successful CTO PCI in a single high-volume CTO PCI center (175 procedures/year). Changes in perfusion defect size (in myocardial segments) and hyperemic myocardial blood flow (MBF, in mL min–1 g–1) within the CTO territory after PCI were related to the combined endpoint of death or myocardial infarction (MI). Kaplan-Meier curves (log-rank test) and multivariable Cox regression (including covariates age, gender, prior MI, and left ventricular function) were used to analyze unadjusted and risk-adjusted event-free survivals with HR [95% CI]. Results Out of 213 (97%) patients with a median follow-up of 3.2 [2.1–4.7] years, 22 (10%) patients experienced the composite of death (19, 9%) or MI (5, 2%). Event-free survival was significantly improved in patients with a perfusion defect size reduction of ≥3 segments (N=132, 62%) after CTO PCI compared to 1.13 mL min–1 g–1) as compared to below the median (p2.30 mL min–1 g–1 (N=105, 49%) showed a better event-free survival compared to patients with lower residual hyperemic MBF levels (p=0.02, risk-adjusted: p=0.04 with HR 0.33 [0.12–0.95]). Conclusions Patients with more ischemic burden reduction and less residual ischemia following CTO PCI showed a major improved survival free of death or MI. A limitation was the low absolute number of events that prohibited more extensive risk-adjustment of the analyses. Funding Acknowledgement Type of funding source: None

Background A myocardial ischemic burden (IB) of 10% is used to denote high-risk patients with coronary artery disease (CAD). This threshold has primarily been assessed by single-photon emission computed tomography. Differences in the pharmacokinetics of the utilized traces, higher resolution of positron emission tomography (PET), and lastly differences in assessment of IB might lead to a higher prognostic threshold for quantitative PET. Purpose To determine a [15O]H2O PET derived IB to identify low (annualized event rate (AER) Methods 623 patients who underwent [15O]H2O PET because of suspected CAD and in whom follow-up was obtained were included. The IB was defined as the percentage of myocardium with a hyperemic blood flow (hMBF) ≤2.3 ml/min/g and by a coronary flow reserve (CFR) of ≤2.5. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Time-dependent ROC curves were constructed for the prediction of the endpoint within the first 5-years, based on these curves thresholds were selected for which specificity was maximized and sensitivity was at least 80%. Patients were classified as having a high IB if their respective IBs were above the prognostic thresholds and as having a low IB if not. Results During a median follow-up of 6.7 years, 34 (6%) patients died and 28 (4%) experienced a MI resulting in 62 (10%) endpoints. An IB of 24% and 28% for hMBF and CFR, respectively, was found to be the optimal threshold to define prognosis. Patients with a high hMBF or high CFR IB had worse outcome compared to patients with a low IB (log-rank p Conclusion An IB of 24% and 28% for hMBF and CFR was found to be the optimal prognostic threshold. Both measurements can be used to determine patients outcome. However combining hMBF and CFR IB results leads to a further refinement of risk-stratification allowing for the identification of low (concordant low or discordant IB result) and high (concordant high IB result) risk CAD patients. Funding Acknowledgement Type of funding source: None

Aims This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD). Methods and results In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8–7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P, Graphical Abstract Graphical Abstract

OBJECTIVES This study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)-defined coronary artery disease (CAD).BACKGROUND QFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.METHODS A total of 208 (624 vessels) patients underwent technetium -99m tetrofosmin SPECT and [15O]H2O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).RESULTS QFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.CONCLUSIONS In this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFRdefined significant CAD compared with perfusion imaging by SPECT or PET. (J Am Coll Cardiol Img 2020;13:1976-85) (c) 2020 by the American College of Cardiology Foundation.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described.

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the “collaborative organizational model” of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition.

Aims To evaluate the prognostic value of global and regional quantitative [15O]H2O positron emission tomography (PET) perfusion. Methods and results In this retrospective study, 648 patients with suspected or known coronary artery disease (CAD) who underwent [15O]H2O PET were followed for the occurrence of death and myocardial infarction (MI). Global and regional hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) were obtained from [15O]H2O PET. During median follow-up of 6.9 (5.0–7.9) years, 64 (9.9%) patients experienced the composite of death (36–5.6%) and MI (28–4.3%). Impaired global hMBF ( Conclusion Global and regional hMBF and CFR were all prognostic factors for death and MI. However, for both global and regional perfusion, hMBF remained the only independent prognostic factor after adjusting for the combined use of hMBF and CFR. Additionally, integrating global and regional perfusion did not increase prognostic performance compared to either regional or global perfusion alone.

Using [18F] Sodium Fuoride (NaF) Positron Emission Tomography (PET) it is not only possible to identify the ossifying potency of a flare‐up, but also to identify an asymptomatic chronic stage of fibrodysplasia ossificans progressiva (FOP). The purpose of this study was to investigate the diagnostic role of a more widely available imaging modality, Magnetic Resonance Imaging (MRI), which is of special interest for studies in pediatric FOP patients. MRI and [18F]NaF PET/CT images at time of inclusion and subsequent follow‐up CT scans of 4 patients were analyzed retrospectively. Presence, location, and intensity of edema identified by MRI were compared with activity on [18F]NaF PET. Occurrence or progression of heterotopic ossification (HO) was examined on the follow‐up CT images. Thirteen different lesions in various muscle groups were identified: five lesions with only edema, five lesions with both edema and increased [18F]NaF uptake, one lesion with only increased [18F]NaF uptake, and two lesions with neither edema nor uptake of [18F]NaF. Mild edema, found in three lesions, was present at asymptomatic sites, which did not show increased [18F] NaF uptake or progression of HO on consecutive CT images. Moderate edema was found in three symptomatic lesions, with increased [18F]NaF on PET and progression of HO on CT. Severe edema was identified in four lesions. Interestingly, two of these lesions did not develop HO during follow‐up; one of these two even gave obvious symptoms of a flare‐up. MRI can identify whether symptoms are the result of an acute flare‐up by the presence of moderate to severe edema. The occurrence of severe edema on MRI was not always related to an ossifying lesion. The additional diagnostic value of MRI requires further investigation, but MRI does not seem to fully replace the diagnostic characteristics of [18F]NaF PET/CT in FOP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disease, characterized by the formation of heterotopic ossification (HO) in muscles, ligaments, and tendons. Flare-ups, an inflammatory process that often precedes the formation of HO, can occur spontaneously, but trauma is also a common trigger. It is not known whether radiotherapy, especially in higher doses, might cause sufficient trauma or inflammation to trigger a flare-up and subsequent HO in FOP patients. We report the case of a patient undergoing radiotherapy for the treatment of a 1-cm-wide basal cell carcinoma (BCC) of the lower lip. In addition, we present a systematic review of the available literature. Our patient received 54 Gy in 18 fractions with orthovoltage therapy, resulting in a clinical complete response of the tumor. Six months after treatment, there were no signs of HO either clinically or on [18F]NaF PET/CT. The systematic review identified 11 publications describing either radiation treatment in FOP or radiation therapy as a cause of HO in non-FOP patients. Six case reports described the use of radiation in FOP patients for various reasons, including one with a high-dose treatment of a lip BCC using superficial X-ray therapy. The remaining five studies described the use of low-dose radiotherapy to prevent or treat either an FOP flare-up or HO formation. None of these cases showed worsening of disease that could be attributed to the use of radiation therapy. Radiation induced HO in non-FOP patients was rare and occurred in five studies. The largest of these studies suggested that HO was induced after treatment with high doses, resulting in more widespread evidence of tissue damage, potentially being the end result of this damage. In conclusion, available reports suggest no contraindication to radiotherapy in FOP patients; although the number of cases was small, systematic toxicity reports often were not available, and none of the reports described high-dose, high-energy radiation treatment at locations such as muscle and joint regions.

Background: Scan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner. Methods: Two-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor. Results: Distribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247). Conclusion: Diagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.

Objectives This study sought to compare Doppler flow velocity reserve (CFRDoppl) and thermodilution-derived coronary flow reserve (CFRthermo) head-to-head with the gold standard for quantification of myocardial perfusion, [15O]H2O positron emission tomography (PET). Background Coronary flow reserve (CFR) is an important parameter for assessing coronary vascular function. To date, 2 techniques are available for invasive assessment of CFR: Doppler flow velocity and thermodilution. Although these techniques have been compared with each other, neither has been compared with [15O]H2O PET perfusion imaging. Methods CFR was assessed in 98 vessels of 40 consecutive stable patients with suspected coronary artery disease. Patients underwent [15O]H2O PET, followed by invasive angiography in conjunction with simultaneous measurements of fractional flow reserve, CFRDoppl, and CFRthermo. Both normal and obstructed arteries were included. Results The quality of Doppler flow velocity traces was significantly lower than that of thermodilution curves (p Conclusions Coronary flow reserve, determined using Doppler flow velocity, has superior agreement with [15O]H2O PET in comparison with CFRthermo.

Scan quality directly impacts the diagnostic performance of non-invasive imaging modalities as reported in a substudy of the PACIFC-trial: “Impact of Scan Quality on the Diagnostic Performance of CCTA, SPECT, and PET for Diagnosing Myocardial Ischemia Defined by Fractional Flow Reserve” [1]. This Data-in-Brief paper supplements the hereinabove mentioned article by presenting the diagnostic performance of CCTA, SPECT, and PET on a per vessel level for the detection of hemodynamic significant coronary artery disease (CAD) when stratified according to scan quality and vascular territory. Keywords: Coronary artery disease, Fractional flow reserve, Coronary computed tomography angiography, Single photon emission computed tomography, Positron emission tomography

Background: Fluorodeoxyglucose positron emission tomography (FDG-PET) is a novel method of assessing suspected periprosthetic hip infection. However, a heterogeneity of sensitivity and specificity using different diagnostic criteria across clinical studies has been published. The objective of this study is to evaluate the various diagnostic criteria using FDG-PET in diagnosing periprosthetic hip infection. Methods: FDG-PET scans of patients suffering from painful hip prostheses between 2008 and 2015 were retrospectively reviewed. The PET images were considered positive for infection using five criteria: any increased uptake at the (1) bone-prosthesis-interface, (2) periprosthetic soft tissue (PST), or (3) both, (4) increased uptake in the bone-prosthesis-interface compared to the PST, and (5) increased uptake along the femoral bone-prosthesis-interface. The final diagnosis of infection was based on the pre-operative and intra-operative findings with clinical follow-up > 12 months. Results: A total of 33 hip prostheses were evaluated in this study, of which 16 were determined to be infected and 17 uninfected. Any periprosthetic FDG uptake was found in all symptomatic prostheses (sensitivity 100%; specificity 0%). When increased uptake in the bone-prosthesis-interface (sensitivity 100%; specificity 65%) or PST (sensitivity 94%; specificity 59%) was considered infected, specificity increased. A higher intensity of uptake at the bone-prosthesis-interface than PST demonstrated only moderate specificity (sensitivity 44%; specificity 71%). The most specific criterion for infection was an increased FDG uptake along the femoral bone-prosthesis-interface (sensitivity 81%; specificity 94%). Conclusions: Our results demonstrated that the accuracy of FDG-PET is highly dependent of the diagnostic criteria used for periprosthetic hip infection. Only an acceptable diagnostic accuracy (sensitivity 81%; specificity 94%) was found when increased FDG uptake along the femoral bone-prosthesis-interface was considered positive for infection.

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.

Item does not contain fulltext Aims: Guidelines recommend the use of fractional flow reserve (FFR) to guide percutaneous coronary intervention. For this purpose, physiological lesion assessment without adenosine may have a similar diagnostic accuracy as FFR. We aimed to investigate the performances of FFR, resting instantaneous wave-free ratio (iFR), and resting Pd/Pa compared with [15O]H2O positron emission tomography (PET) perfusion imaging. Methods and results: [15O]H2O PET and intracoronary pressure measurements were evaluated in 320 coronary arteries (of which 136 coronary stenoses) in 129 stable patients. The primary analysis consisting of the area-under-the-receiver-operating-characteristic curve for impaired PET hyperaemic myocardial blood flow (MBF)

BACKGROUND: In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate technique.QUESTIONS/PURPOSES: To perform a meta-analysis to compare the accuracy of various applied imaging modalities in the assessment of periprosthetic knee infection.METHODS: A systematic review and meta-analysis was conducted with a comprehensive search of MEDLINE and Embase® in accordance with the PRISMA and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) recommendations to identify clinical studies in which periprosthetic knee infection was investigated with different imaging modalities. The sensitivity and specificity of each imaging technique were determined and compared with the results of microbiologic and histologic analyses, intraoperative findings, and clinical followup of more than 6 months. A total of 23 studies, published between 1990 and 2015, were included for meta-analysis, representing 1027 diagnostic images of symptomatic knee prostheses. Quality of the included studies showed low concerns regarding external validity, whereas internal validity indicated more concerns regarding the risk of bias. The most important concerns were found in the lack of uniform criteria for the diagnosis of a periprosthetic infection and the flow and timing of the included studies. Differences among techniques were tested at a probability less than 0.05 level. Where there was slight overlap of confidence intervals for two means, it is possible for the point estimates to be statistically different from one another at a probability less than 0.05. The z-test was used to statistically analyze differences in these situations.RESULTS: Bone scintigraphy was less specific than all other modalities tested (56%; 95% CI, 0.47-0.64; p < 0.001), and leukocyte scintigraphy (77%; 95% CI, 0.69-0.85) was less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p < 0.001) or combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Fluorodeoxyglucose positron emission tomography (FDG-PET) (84%; 95% CI, 0.76-0.90) was more specific than bone scintigraphy (56%; 95% CI, 0.47-0.64; p < 0.001), and less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p = 0.02) and combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Leukocyte scintigraphy (88%; 95% CI, 0.81-0.93; p = 0.01) and antigranulocyte scintigraphy (90%; 95% CI, 0.78-0.96; p = 0.02) were more sensitive than FGD-PET (70%; 95% CI, 0.56-0.81). However, because of broad overlapping of confidence intervals, no differences in sensitivity were observed among the other modalities, including combined bone scintigraphy (93%; 95% CI, 0.85-0.98) or combined leukocyte and bone marrow scintigraphy (80%; 95% CI, 0.66-0.91; p > 0.05 for all paired comparisons).CONCLUSIONS: Based on current evidence, antigranulocyte scintigraphy and combined leukocyte and bone marrow scintigraphy appear to be highly specific imaging modalities in confirming periprosthetic knee infection. Bone scintigraphy was a highly sensitive imaging technique but lacks the specificity needed to differentiate among various conditions that cause painful knee prostheses. FDG-PET may not be the preferred imaging modality because it is more expensive and not more effective in confirming periprosthetic knee infection.LEVEL OF EVIDENCE: Level III, diagnostic study.

Noninvasive assessment of coronary artery disease remains a challenging task, with a large armamentarium of diagnostic modalities. Myocardial perfusion imaging (MPI) is widely used for this purpose whereby cardiac positron emission tomography (PET) is considered the gold standard. Next to relative radiotracer distribution, PET allows for measurement of absolute myocardial blood flow. This quantification of perfusion improves diagnostic accuracy and prognostic value. Cardiac hybrid imaging relies on the fusion of anatomical and functional imaging using coronary computed tomography angiography and MPI, respectively, and provides incremental value as compared with either stand-alone modality.

Background: Multiple crossing techniques in chronic total occlusion (CTO) percutaneous coronary intervention have been developed. This study compared recovery of quantitative myocardial blood flow (MBF) after different CTO percutaneous coronary intervention techniques. Methods: Consecutive patients with [ 15 O]H 2 O positron emission tomography perfusion imaging before and 3 months after successful CTO percutaneous coronary intervention between 2013 and 2018 were included. Changes in hyperemic MBF, coronary flow reserve, and perfusion defect size were compared between antegrade wire escalation, retrograde wire escalation, antegrade dissection and reentry (ADR), and retrograde dissection and reentry. Results: One hundred ninety-three patients were treated with antegrade wire escalation (N=90), retrograde wire escalation (N=24), ADR (N=35), and retrograde dissection and reentry (N=44). Increase in hyperemic MBF (1.19±0.77, 0.94±0.65, 1.09±0.63, and 1.02±0.75 mL·min -1 ·g -1 , respectively; P =0.40) and coronary flow reserve (1.34±1.08, 1.14±1.09, 1.31±0.96, and 1.24±0.99, respectively; P =0.84) and decrease in defect size (3.2±2.1, 3.0±2.2, 2.7±2.1, and 2.9±1.9 segments, respectively; P =0.77) were comparable between the 4 approaches. In addition, recovery of hyperemic MBF was less pronounced after subintimal crossing with knuckle-wire-technique compared with CrossBoss in controlled ADR and retrograde dissection and reentry (0.93±0.69 versus 1.54±0.65 mL·min -1 ·g -1 , P =0.02), and less after reentry using subintimal tracking and reentry in ADR compared with controlled ADR (Stingray) or limited antegrade subintimal tracking (0.60±0.53 versus 1.18±0.54 [ P =0.04] and versus 1.49±0.57 mL·min -1 ·g -1 , [ P Conclusions: Recovery of hyperemic MBF, coronary flow reserve, and perfusion defect size after CTO percutaneous coronary intervention was comparable between different approaches. Although sometimes necessary to cross a complex CTO lesion, subintimal knuckle wiring and subintimal tracking and reentry resulted in less hyperemic MBF improvement compared with other subintimal crossing and reentry techniques.

Background Quantitative flow ratio (QFR) uses fast computational algorithms based on 3-dimensional quantitative coronary angiography and estimation of contrast flow velocity during invasive coronary angiography (ICA) to obtain QFR values equivalent to fractional flow reserve (FFR). Objective To compare the diagnostic performance of QFR with coronary computed tomography angiography (CCTA), single-photon emission tomography (SPECT), and positron emission tomography (PET) for diagnosing myocardial ischemia defined by FFR. Method QFR computation was attempted in 109 patients (286 vessels without a subtotal/total lesion) of the 208 patients included in the PACIFIC-trial. Patients underwent 256-slice CCTA, Tetrofosmin SPECT, and [15O]H2O PET prior to ICA in conjunction with 3 vessel FFR measurements. ICA images were obtained without the use of a dedicated QFR acquistion protocol. QFR was calculated using a fixed empiric hyperemic flow velocity (fQFR) as well as using a patient specific flow velocity based on contrast passage through the coronary (cQFR). All analysis were performed on a per vessel level. Results Fixed QFR computation succeeded in 152 (53%) vessels while cQFR analysis was successful in 140 (49%) vessels. A good correlation between FFR and fQFR/cQFR was observed (R=0.774, p Table 1 % (95% Confidence Interval) fQFR n=152 cQFR (n=140) CCTA (n=152) SPECT (n=150) PET (n=149) Sensitivity 76 (59–89) 71 (53–86) 70 (51–84) 30 (16–49) 76 (58–89) Specificity 94 (88–98) 93 (86–97) 73 (64–81) 96 (90–99) 80 (72–87) Negative Predictive Value 93 (88–96) 92 (86–95) 90 (84–94) 83 (79–86) 92 (86–96) Positive Predictive Value 79 (64–89) 74 (59–85) 42 (33–51) 67 (42–84) 52 (42–62) Accuracy 90 (84–94) 88 (81–93) 72 (65–79) 81 (74–87) 79 (72–85) Figure 1. Conclusion Fixed QFR and cQFR correlate well with FFR with a high diagnostic accuracy as result. QFR outperformed CCTA, SPECT, and PET for the diagnosis of myocardial ischemia on a per vessel basis with the important footnote that fQFR and cQFR could only be computed in 53%, and 49% of the vessels.

Background Management of patients with suspected coronary artery disease (CAD) can be optimized with prognostic information derived from non-invasive imaging such as positron emission tomography (PET) perfusion imaging and coronary computed tomography angiography (CCTA). The aim of the present study was to determine the incremental prognostic value of combined functional testing using PET perfusion imaging and anatomical testing using CCTA-derived stenosis severity and morphological assessment of CCTA-derived plaque morphology. Methods In this retrospective study, 539 patients referred for hybrid [15O]H2O PET – CCTA imaging because of suspected CAD were investigated. PET perfusion imaging was used to determine hyperemic myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenosis and high-risk plaque morphology. Major adverse coronary events (MACE) included all-cause death, non-fatal myocardial infarction (MI), urgent revascularization and late non-urgent revascularization (i.e. not guided by initial diagnostic work-up with non-invasive imaging). Kaplan Meier analysis and Cox proportional hazard regression were used to evaluate the independent prognostic value of PET-derived MBF, CCTA-derived stenosis and CCTA-derived high-risk plaque. Results During a mean follow-up of 6.8 [4.8–7.9] years, 79 (14.7%) patients experienced MACE, including 23 (4.3%) deaths, 19 (3.5%) MIs, 8 (1.5%) urgent revascularizations and 29 (5.4%) late non-urgent revascularizations. Annualized event rates for normal vs. abnormal results of PET perfusion imaging, CCTA-derived stenosis and high-risk plaque morphology were 1.2% vs 4.1%, 0.6% vs 4.4%, and 1.7% vs 5.6%, respectively (p MACE-free survival stratified by PET-CT Conclusion PET-derived myocardial blood flow and CCTA-derived stenosis severity and high-risk plaque morphology are independent long-term predictors of adverse cardiac events and provide incremental prognostic value. Combined functional, anatomical and morphological assessment may allow for improved risk stratification in patients with suspected CAD.

Background A low coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as a factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive coronary artery disease (CAD). Objective To elucidate the association of V/M with non-invasively obtained MBF parameters by means of [15O]H2O positron emission tomography (PET), as well as its correlations with invasively measured fractional flow reserve (FFR), overall and specifically in vessel with non-obstructive CAD. Methods This is a substudy of the PACIFIC trial, in which 208 patients underwent CCTA, and [15O]H2O PET prior to invasive coronary angiography (ICA) in conjunction with 3 vessel FFR measurements. Patient specific V/M was calculated for 152 patients. Matched vessel specific hyperemic MBF (hMBF), coronary flow reserve (CFR), FFR, and patient specific V/M were available for 431 vessels. The median V/M (20.71 mm3/g) was used to divide the study population into a group with a low V/M ( Results Overall, a higher percentage of vessels with an abnormal hMBF (34% vs. 19%, p=0.009), lower FFR values (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p=0.016), and a higher number of positive FFR values (20% vs. 9%, p=0.004) were observed among vessels in the low V/M group. Furthermore, a weak correlation between V/M, global hMBF (R=0.179, p=0.027), and global CFR (R=0.163, p=0.045) as well as a weak significant association with vessel specific hMBF (p=0.027), and FFR (p Conclusion Overall, vessels with an abnormal hMBF, and positive FFR measurements were more frequently observed in patients with a low V/M compared to those with a high V/M. Furthermore, V/M weakly correlated with global hMBF as well as with CFR and was associated with vessel specific hMBF and FFR. However, there was no correlation between V/M and global nor vessel specific blood flow parameters in the absence of obstructive CAD, notwithstanding a weak association of V/M with FFR within this group was noted.