Molecular imaging of myocardial αvβ3 integrin expression for evaluation of myocardial injury after human acute myocardial infarction

Background: 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after myocardial infarction and it has been proposed as a marker of myocardial repair. Purpose: We evaluated myocardial 68Ga-NODAGA-RGD uptake, explored its predictors and whether is associated with left ventricular function improvement after human acute myocardial infarction (AMI). Methods: Thirty patients underwent PET scanning at 7.7 ± 3.8 days after primary percutaneous coronary intervention for ST-elevation AMI. PET scan included resting myocardial blood flow (MBF) quantification using 15O-water, as well as 68Ga-NODAGA-RGD scanning 60 minutes after tracer (180 MBq) injection. Patients underwent baseline transthoracic echocardiography, including speckle-tracking chocardiography, at the day of PET scan, and at 6-month follow-up. The definition of the ischemic area at risk and remote myocardial segments was based on the culprit coronary arterial segments in invasive angiography. 68Ga-NODAGA-RGD images were co-registered with perfusion images and uptake was quantified as the maximal absolute standardized uptake value (SUVmax) in the area at risk, and the mean standardized uptake value (SUVmean) in remote segments. In addition to absolute SUVmax, we measured SUVmax in the area at risk corrected to mean MBF in the same area (SUVmax/MBFmean) to account for potentially reduced viable tissue in the area at risk. Results: Mean age was 64.2 ± 9.2 years, 90.3% males. Mean left ventricular ejection fraction (LVEF) was 55.8 ± 6.8%, mean global longitudinal strain (GLS) -14.9 ± 4.5%, and mean global circumferential strain (GCS) -14.0 ± 4.6%. In the ischemic area at risk, mean regional longitudinal strain was -12.5 ± 6.0%, and mean regional circumferential strain -12.7 ± 6.0%. The 68Ga-NODAGA-RGD SUVmax did not correlate with myocardial blood flow in the area at risk. The maximum 68Ga-NODAGA-RGD uptake co-localized with the area at risk in 83.9% of patients, and was present in the segments bordering ischemic area in the rest. Mean SUVmax was higher in the area at risk than SUVmean of the remote myocardium (0.73 ± 0.16 vs. 0.51 ± 0.11, respectively, p<0.001). Univariable predictors of the culprit SUVmax included peak Troponin T (p<0.001), peak ProBNP (p<0.001), low LVEF (p=0.055), low GLS (p=0.01), low GCS (p=0.057), low regional longitudinal strain in the area at risk (p=0.02), and low circumferential strain in the area at risk (p=0.01). In multivariable analysis, peak proBNP independently predicted SUVmax in the area at risk (p<0.001). In univariable analysis, the absolute SUVmax in the area at risk predicted improvement of GLS indexed to baseline GLS (p=0.04). Furthermore, the normalized culprit SUVmax/MBFmean predicted improvement of LVEF indexed to baseline LVEF (p=0.058), improvement of GLS (p=0.04), improvement of GLS indexed to baseline GLS (p<0.001), and improvement of GCS indexed to baseline GCS (p=0.02). Conclusions: In patients with AMI, 68Ga-NODAGA-RGD uptake increased in the ischemic area at risk, and it was associated with the extent of myocardial injury, both global and regional systolic dysfunction, and increased left ventricular filling pressure. Moreover, 68Ga-NODAGA-RGD uptake predicts global left ventricular functional improvement at mid-term follow-up. Imaging of αvβ3 integrin is a potential approach to evaluate myocardial repair processes after AMI.Tausta: Sydäninfarktin jälkeen käynnistyy sydänlihaksen korjausmekanismeja, jotka pyrkivät ylläpitämään sydämen toimintaa. Angiogeneesi on yksi korjausmekanismeista. Verisuonen solupinnan glykoproteiinireseptori αvβ3-integriini lisääntyy angiogeneesin aikana ja sitä on käytetty merkkinä angiogeneesin aktiivisuudesta. Aiemmissa tutkimuksissa on osoitettu αvβ3-integriinin lisääntyvän infarktoituneella alueella. 86Ga-NODAGA-RGD on radioaktiivinen merkkiaine, joka on suunniteltu αvβ3-integriinin kuvantamiseen positroniemissiotomografia (PET)-tekniikalla. Edelleen on kuitenkin selvittämättä auttaako 86Ga-NODAGA-RGD-PET sydäninfarktivaurion ja sen paranemisen arvioimisessa akuutin sydäninfarktin jälkeen. Metodit: Tutkimukseen rekrytoitiin 31 ensimmäisen akuutin ST-nousuinfarktin sairastanutta potilasta, joille tehtiin onnistuneesti päivystyksellinen sepelvaltimoiden pallolaajennustoimenpide ja joilla todettiin sydämen vasemman kammion systolinen toimintahäiriö (ejektiofraktio <50%). 7,7 ± 3,8 päivää akuutin sydäninfarktin jälkeen potilaille tehtiin 86Ga-NODAGA-RGD-PET-tutkimus, PET-perfuusiotutkimus sekä sydämen ultraäänitutkimus. Sydämen vasemman kammion toimintaa mitattiin alueellisella supistuvuudella eli strainilla. 6 kuukauden seurantajakson jälkeen toistettiin sydämen kaikututkimus. Sydänlihaksen 86Ga-NODAGA-RGD kertymää verrattiin tukkeutuneen sepelvaltimon suonittamalla alueella muuhun sydänlihakseen. Tulokset: 68Ga-NODAGA-RGD merkkiaineen kertymä oli lisääntynyt tukkeutuneen sepelvaltimon suonittamalla alueella kaikilla potilailla. Potilaista 84 %:lla korkein mitattu merkkiainepitoisuus (SUVmax) havaittiin tukkeutuneen sepelvaltimon suonittamalla alueella ja lopuilla välittömästi sen vieressä. Korkein tukkeutuneen sepelvaltimon suonittamalla alueella mitattu 68Ga-NODAGA-RGD:n pitoisuus oli korkeampi kuin keskimäärin terveessä sydänlihaksessa (0.73 ± 0.16 vs. 0.51 ± 0.11, p<0.001). Yksimuuttuja-analyysissä infarktialueen 68Ga-NODAGA-RGD-kertymän ennustetekijöitä olivat kohonnut sydänlihasvaurion merkkiainepitoisuus (troponiini T, p<0.001), kohonnut natriureettisen peptidin pitoisuus (proBNP, p<0.001), heikentynyt lähtötilanteen vasemman kammion ejektiofraktio (p<0.001), heikentynyt lähtötilanteen strain sekä koko vasemmassa kammiossa että infarktialueella (p<0.001). Seurannassa selvisi, että infarktialueen kohonnut merkkiainepitoisuus oli yhteydessä parantuneeseen vasemman kammion ejektiofraktioon lähtötilanteeseen verrattuna (p=0.058) ja parantuneeseen koko vasemman kammion strainiin (p<0.001) Pohdinta: Tutkimus osoitti, että angiogeneesin merkkiaineen, 86Ga-NODAGA-RGD, kertymä lisääntyy tukkeutuneeseen sepelvaltimon suonittamalla alueella akuutin sydäninfarktin jälkeen. Suurentunut kertymä näyttää yhtäältä liittyvän suureen sydänlihasvaurioon ja sydämen toimintahäiriöön ja toisaalta ennustavan sydämen toiminnan paranemista. Merkkiaineen kliininen hyödyntäminen vaatii vielä jatkotutkimuksia. Mahdollisesti 86Ga-NODAGA-RGD:tä voidaan hyödyntää sydämen vajaatoimintaa ehkäisevien hoitojen ja lääkkeiden tutkimisen apuna

False consensus in situational judgment tests: What would others do?

We introduce an alternative response instruction to reduce the fakability of situational judgment tests. This novel instruction is based on the false consensus effect, a robust social psychological bias whereby people infer that the majority of other people's thoughts, attitudes, and behaviors are aligned with their own. In four studies, including both field and laboratory data (total N = 882), we demonstrate that participants show a false consensus bias when asked what others would do in situational judgment tests. Furthermore, the situational judgment test based on the false consensus effect turned out to relatively difficult to be fake, and produced scores that were meaningfully correlated with conceptually related traits, as well as both self-reported and behavioral outcomes

Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry

BACKGROUND The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS). METHODS Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD). RESULTS The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization. CONCLUSIONS In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior

Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.

BACKGROUND: The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS). METHODS: Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD). RESULTS: The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization. CONCLUSIONS: In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior

Three Nightmare Traits in Leaders

This review offers an integration of dark leadership styles with dark personality traits. The core of dark leadership consists of Three Nightmare Traits (TNT)—leader dishonesty, leader disagreeableness, and leader carelessness—that are conceptualized as contextualized personality traits aligned with respectively (low) honesty-humility, (low) agreeableness, and (low) conscientiousness. It is argued that the TNT, when combined with high extraversion and low emotionality, can have serious (“explosive”) negative consequences for employees and their organizations. A Situation-Trait-Outcome Activation (STOA) model is presented in which a description is offered of situations that are attractive to TNT leaders (situation activation), situations that activate TNT traits (trait activation), and the kinds of outcomes that may result from TNT behaviors (outcome activation). Subsequently, the TNT and STOA models are combined to offer a description of the organizational actions that may strengthen or weaken the TNT during six career stages: attraction, selection, socialization, production, promotion, and attrition. Except for mainly negative consequences of the TNT, possible positive consequences of TNT leadership are also explored, and an outline of a research program is offered that may provide answers to the most pressing questions in dark leadership research