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.

Functional stress imaging to predict abnormal coronary fractional flow reserve: the PACIFIC 2 study.

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 < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI). 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.

Worldwide Variation in the Use of Nuclear Cardiology Camera Technology, Reconstruction Software, and Imaging Protocols.

OBJECTIVES: This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED). BACKGROUND: Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols. METHODS: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study) registry, a multinational, cross-sectional study comprising 7,911 imaging studies from 308 labs in 65 countries. The study compared regional use of camera technologies, advanced post-processing software, and protocol characteristics and analyzed the influence of each factor on ED. RESULTS: Cadmium-zinc-telluride and positron emission tomography (PET) cameras were used in 10% (regional range 0% to 26%) and 6% (regional range 0% to 17%) of studies worldwide. Attenuation correction was used in 26% of cases (range 10% to 57%), and advanced post-processing software was used in 38% of cases (range 26% to 64%). Stress-first single-photon emission computed tomography (SPECT) imaging comprised nearly 20% of cases from all world regions, except North America, where it was used in just 7% of cases. Factors associated with lower ED and odds ratio for achieving radiation dose ≤9 mSv included use of cadmium-zinc-telluride, PET, advanced post-processing software, and stress- or rest-only imaging. Overall, 39% of all studies (97% PET and 35% SPECT) were ≤9 mSv, while just 6% of all studies (32% PET and 4% SPECT) achieved a dose ≤3 mSv. CONCLUSIONS: Newer-technology cameras, advanced software, and stress-only protocols were associated with reduced ED, but worldwide adoption of these practices was generally low and varied significantly between regions. The implementation of dose-optimizing technologies and protocols offers an opportunity to reduce patient radiation exposure across all world regions.

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS.

OBJECTIVES: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). BACKGROUND: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. METHODS: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. RESULTS: The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. CONCLUSIONS: This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.

Anatomical and functional coronary imaging to predict long-term outcome in patients with suspected coronary artery disease: the EVINCI-outcome study.

AIMS: To investigate the prognostic relevance of coronary anatomy, coronary function, and early revascularization in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: From March 2009 to June 2012, 430 patients with suspected CAD (61 ± 9 years, 62% men) underwent coronary anatomical imaging by computed tomography coronary angiography (CTCA) and coronary functional imaging followed by invasive coronary angiography (ICA) if at least one non-invasive test was abnormal. Obstructive CAD was documented by ICA in 119 patients and 90 were revascularized within 90 days of enrolment. Core laboratory analysis showed that 134 patients had obstructive CAD by CTCA (>50% stenosis in major coronary vessels) and 79 significant ischaemia by functional imaging [>10% left ventricular (LV) myocardium]. Over mean follow-up of 4.4 years, major adverse events (AEs) (all-cause death, non-fatal myocardial infarction, or hospital admission for unstable angina or heart failure) or AEs plus late revascularization (LR) occurred in 40 (9.3%) and 58 (13.5%) patients, respectively. Obstructive CAD at CTCA was the only independent imaging predictor of AEs [hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.10-9.30; P = 0.033] and AEs plus LR (HR 4.3, 95% CI 1.56-11.81; P = 0.005). Patients with CAD in whom early revascularization was performed in the presence of ischaemia and deferred in its absence had fewer AEs, similar to patients without CAD (HR 2.0, 95% CI 0.71-5.51; P = 0.195). CONCLUSION: Obstructive CAD imaged by CTCA is an independent predictor of clinical outcome. Early management of CAD targeted to the combined anatomical and functional disease phenotype improves clinical outcome.

Adenosine single-photon emission computed tomography-derived transient ischemic dilatation and ejection fraction reserve fail to predict multivessel coronary artery disease.

Next to myocardial perfusion, single-photon emission computed tomography (SPECT) also allows for the assessment of nonperfusion parameters such as transient ischemic dilatation (TID) and a reduction of ejection fraction (EF) with stress imaging. This study aimed to evaluate the diagnostic value of TID and EF reserve for the detection of significant multivessel coronary artery disease (CAD). A total of 206 patients with suspected stable CAD prospectively underwent gated stress-rest Tc-tetrofosmin SPECT and invasive coronary angiography with routine fractional flow reserve (FFR) measurements, irrespective of imaging results. Left ventricular volumes, TID, and EF reserve were assessed and compared with FFR-defined severity of CAD. According to FFR, 92 (45%) patients had significant CAD, whereas 25 (12%) showed 2-vessel disease (VD) and 22 (11%) showed 3-VD. With an increasing extent of CAD, TID values and EF reserve did not change significantly (P=0.07 and 0.42 for trend, respectively). Conversely, absolute left ventricular volumes and EF differed significantly among groups of CAD severity (P<0.01 for all trends). SPECT-derived TID and EF reserve did not differ between patients with high-risk CAD (3-VD) and low risk or no significant CAD. Therefore, the present results advocate exerting caution when using these ancillary findings in clinical practice.

Comparison of Coronary Computed Tomography Angiography, Fractional Flow Reserve, and Perfusion Imaging for Ischemia Diagnosis.

BACKGROUND: Fractional flow reserve (FFR) computation from coronary computed tomography angiography (CTA) datasets (FFRCT) has emerged as a promising noninvasive test to assess hemodynamic severity of coronary artery disease (CAD), but has not yet been compared with traditional functional imaging. OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance of FFRCT and compare it with coronary CTA, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) for ischemia diagnosis. METHODS: This subanalysis involved 208 prospectively included patients with suspected stable CAD, who underwent 256-slice coronary CTA, 99mTc-tetrofosmin SPECT, [15O]H2O PET, and routine 3-vessel invasive FFR measurements. FFRCT values were retrospectively derived from the coronary CTA images. Images from each modality were interpreted by core laboratories, and their diagnostic performances were compared using invasively measured FFR ≤0.80 as the reference standard. RESULTS: In total, 505 of 612 (83%) vessels could be evaluated with FFRCT. FFRCT showed a diagnostic accuracy, sensitivity, and specificity of 87%, 90%, and 86% on a per-vessel basis and 78%, 96%, and 63% on a per-patient basis, respectively. Area under the receiver-operating characteristic curve (AUC) for identification of ischemia-causing lesions was significantly greater for FFRCT (0.94 and 0.92) in comparison with coronary CTA (0.83 and 0.81; p < 0.01 for both) and SPECT (0.70 and 0.75; p < 0.01 for both), on a per-vessel and -patient level, respectively. FFRCT also outperformed PET on a per-vessel basis (AUC 0.87; p < 0.01), but not on a per-patient basis (AUC 0.91; p = 0.56). In the intention-to-diagnose analysis, PET showed the highest per-patient and -vessel AUC followed by FFRCT (0.86 vs. 0.83; p = 0.157; and 0.90 vs. 0.79; p = 0.005, respectively). CONCLUSIONS: In this study, FFRCT showed higher diagnostic performance than standard coronary CTA, SPECT, and PET for vessel-specific ischemia, provided coronary CTA images were evaluable by FFRCT, whereas PET had a favorable performance in per-patient and intention-to-diagnose analysis. Still, in patients in whom 3-vessel FFRCT could be analyzed, FFRCT holds clinical potential to provide anatomic and hemodynamic significance of coronary lesions.

Systematic review of cost-effectiveness of myocardial perfusion scintigraphy in patients with ischaemic heart disease: A report from the cardiovascular committee of the European Association of Nuclear Medicine. Endorsed by the European Association of Cardiovascular Imaging.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Variability of radiation doses of cardiac diagnostic imaging tests: the RADIO-EVINCI study (RADIationdOse subproject of the EVINCI study).

BACKGROUND: Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study-EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease). METHODS: We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60 ± 9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean. RESULTS: Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9.6 mSv (IQR = 13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR = 2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR = 1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR = 7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%). CONCLUSION: Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques. TRIAL REGISTRATION: The study protocol is available at https://www.clinicaltrials.gov/ (ClinicalTrials.gov Identifier: NCT00979199 ). Information provided on September 16, 2009.

Nuclear Cardiology Practices and Radiation Exposure in the Oceania Region: Results From the IAEA Nuclear Cardiology Protocols Study (INCAPS).

BACKGROUND: There is concern about radiation exposure with radionuclide myocardial perfusion imaging (MPI). This sub-study of the International Atomic Energy Agency (IAEA) Nuclear Cardiology Protocols Study reports radiation doses from MPI, and use of dose-optimisation protocols in Australia and New Zealand (ANZ), and compares them with data from the rest of the world. METHODS: Data were collected from 7911 MPI studies performed in 308 laboratories worldwide in one week in 2013, including 439 MPI studies from 34 ANZ laboratories. For each laboratory, effective radiation dose (ED) and a quality index (QI) score (out of 8) based on pre-specified "best practices" was determined. RESULTS: In ANZ patients, ED ranged from 0.9-17.9 milliSievert (mSv). Median ED was similar in ANZ compared with the rest of the world (10.0 (IQR: 6.5-11.7) vs. 10.0 (IQR 6.4-12.6, P=0.15), as were mean QI scores (5.5±0.7 vs. 5.4±1.3, P=0.84). Use of stress-only imaging (17.6% vs. 31.8% of labs, P=0.09) and weight-based dosing of technetium-99m (14.7% vs. 30.3%, P=0.07) was lower in ANZ compared with the rest of the world but this difference was not statistically significant. Median ED was significantly lower in metropolitan versus non-metropolitan laboratories (10.1 mSv vs. 11.6 mSv, P<0.01), although mean QI scores were similar (5.4±0.8 vs. 5.5±0.7, P=0.75). CONCLUSION: Across ANZ, there is variability in ED from MPI, and use of radiation safety practices, particularly between metropolitan and non-metropolitan laboratories. Overall, ANZ laboratories have a similar median ED to laboratories in the rest of the world.

Inhaled Aerosol Distribution in Human Airways: A Scintigraphy-Guided Study in a 3D Printed Model.

BACKGROUND: While it is generally accepted that inertial impaction will lead to particle loss as aerosol is being carried into the pulmonary airways, most predictive aerosol deposition models adopt the hypothesis that the inhaled particles that remain airborne will distribute according to the gas flow distribution between airways downstream. METHODS: Using a 3D printed cast of human airways, we quantified particle deposition and distribution and visualized their inhaled trajectory in the human lung. The human airway cast was exposed to 6 µm monodisperse, radiolabeled aerosol particles at distinct inhaled flow rates and imaged by scintigraphy in two perpendicular planes. In addition, we also imaged the distribution of aerosol beyond the airways into the five lung lobes. The experimental aerosol deposition patterns could be mimicked by computational fluid dynamic (CFD) simulation in the same 3D airway geometry. RESULTS: It was shown that for particles with a diameter of 6 µm inhaled at flows up to 60 L/min, the aerosol distribution over both lungs and the individual five lung lobes roughly followed the corresponding distributions of gas flow. While aerosol deposition was greater in the main bronchi of the left versus right lung, distribution of deposited and suspended particles toward the right lung exceeded that of the left lung. The CFD simulations also predict that for both 3 and 6 µm particles, aerosol distribution between lung units subtending from airways in generation 5 did not match gas distribution between these units and that this effect was driven by inertial impaction. CONCLUSIONS: We showed combined imaging experiments and CFD simulations to systematically study aerosol deposition patterns in human airways down to generation 5, where particle deposition could be spatially linked to the airway geometry. As particles are negotiating an increasing number of airways in subsequent branching generations, CFD predicts marked deviations of aerosol distribution with respect to ventilation distribution, even in the normal human lung.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population.

AIMS: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial.

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. METHODS AND RESULTS: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2 ) on exercise, BNP, E/e', LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e' (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema. CONCLUSION: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation.

Noninvasive cardiac imaging in suspected acute coronary syndrome.

Noninvasive cardiac imaging has an important role in the assessment of patients with acute-onset chest pain. In patients with suspected acute coronary syndrome (ACS), cardiac imaging offers incremental value over routine clinical assessment, the electrocardiogram, and blood biomarkers of myocardial injury, to confirm or refute the diagnosis of coronary artery disease and to assess future cardiovascular risk. This Review covers the current guidelines and clinical use of the common noninvasive imaging techniques, including echocardiography and stress echocardiography, computed tomography coronary angiography, myocardial perfusion scintigraphy, positron emission tomography, and cardiovascular magnetic resonance imaging, in patients with suspected ACS, and provides an update on the developments in noninvasive imaging techniques in the past 5 years.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

OBJECTIVE: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. APPROACH AND RESULTS: Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). CONCLUSIONS: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.

Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries.

PURPOSE: Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. METHODS: In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). RESULTS: Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 ± 3.4 mSv (RoW 11.4 ± 4.3 mSv; P < 0.001) and of PET was 2.6 ± 1.5 mSv (RoW 3.8 ± 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 ± 1.2, which was higher than the RoW score (5.0 ± 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. CONCLUSION: In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice.

Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.