Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.

BACKGROUND: Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging. METHOD AND RESULTS: Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUVmax 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUVmean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUVmean uptake, the latter with a very strong correlation with remote uptake (R2 = .74, P < .01). CONCLUSION: Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.

ANTECEDENTES: Proteína de activación de fibroblastos (FAP) como marcador específico de fibroblastos maduros activados se puede visualizar mediante tomografía por emisión de positrones (PET) usando inhibidores de Ga-68-FAP (FAPI). El FAPI marcado con galio 68 se usa cada vez más en la estatificación de varios tipos de cáncer.Además, se han reportado los primeros casos de abordajes teranósticos. En este trabajo describimos el fenómeno de la captación de FAPI miocárdica en pacientes que recibieron Ga-68 FAPI PET para estatificación tumoral. MéTODO Y RESULTADOS: Los exámenes de PET Ga-68 FAPI para estadificación de cáncer se analizaron retrospectivamente con respecto a la captación del marcador cardíaco. Los valores de absorción estandarizados (SUV) se correlacionaron con covariables clínicas en un modelo de regresión univariante. Del 09/2018 al 11/2019 con una n = 32 pacientes fueron sometidos a PET FAPI en nuestra institución. Seis de 32 pacientes (18.8%) demostraron un aumento de acumulación del marcador localizado en el miocardio, con la captación remota de FAPI siendo significativamente mayor en pacientes con aumento de la captación vs sin captación focalizada de miocardio (SUVmax 2.2 ± 0.6 vs. 1.5 ± 0.4, p <0.05 y SUV mean 1.6 ± 0.4 vs. 1.2 ± 0.3, p <0.05, respectivamente). La regresión univariante demostró una correlación significativa de la enfermedad de la arteria coronaria (CAD), la edad y la fracción de eyección ventricular izquierda (FEVI) con absorción SUV remota, esta última con una muy fuerte correlación con la captación remota (R² = 0.74, p <0.01). CONCLUSIóN: Nuestro estudio indica una asociación de CAD, edad y FEVI con la captación de FAPI. Se necesitan más estudios para evaluar si la activación de fibroblastos se puede medir de manera confiable y se puede usar para la estratificación de riesgo con respecto a la detección temprana o la progresión de la CAD y la remodelación ventricular izquierda.

CONTEXTE: La protéine d'activation des fibroblastes (FAP) activés et matures peut être visualisée par tomographie à émission de positons (TEP) à l'aide d'inhibiteurs de l'activation des fibroblastes (FAPI). FAPI marqué au gallium 68 est de plus en plus utilisé dans la stratification de divers cancers. De plus, les premiers exemples d'approches théranostiques ont été rapportés. Dans ce travail nous décrivons la captation myocardique de FAPI chez les patients qui bénéficié d'une TEP au Ga-68 FAPI pour stratification tumorale. MéTHODE ET RéSULTATS: Les examens TEP Ga-68 FAPI pour la stratification oncologique ont été analysés rétrospectivement pour l'absorption du traceur au niveau cardiaque. Les valeurs d'absorption normalisées (SUV) font été corrélées aux variables cliniques selon un modèle de régression univarié. A partir de septembre 2018 jusqu'en novembre 2019, 32 patients ont bénéficié d'une TEP FAPI dans notre établissement. Six de nos 32 patients (18,8%) ont démontré une augmentation focale de captation du tracer au niveau myocardique. Les foyers systémiques se sont révélés significativement plus élevé chez les patients avec foyers myocardiques localisés (SUV max 2,2 ± 0,6 vs 1,5 ± 0,4, p <0,05 et SUV mean 1,6 ± 0,4 vs 1,2 ± 0,3, p <0,05, respectivement). Nous avons observé une corrélation significative entre la maladie coronarienne, l'âge, la fraction d'éjection du ventricule gauche et la présence de foyer myocardiques FAPI (R² = 0,74, p <0,01) CONCLUSION: Notre étude indique une association entre la maladie cardiovasculaire coronarienne, l'âge et la FEVG et la captation myocardique de FAPI. Des études additionnelles sont nécessaires pour déterminer si l'activation des fibroblastes peut être mesurée de manière fiable et utilisée pour la détection et la progression de la maladie coronarienne et le remodelage du ventricule gauche.

[Biomarkers in cardio-oncology patients]. / Biomarker bei onkokardiologischen Patienten.

In recent decades, major advances in the treatment of malignant diseases have significantly improved long-term survival. However, this has increased the spectrum of side effects of these treatment methods, particularly for the cardiovascular system. Cardiotoxicity can be acute and chronic, including hypertension, heart failure, arrhythmias, acute myocardial infarction, venous thromboembolism, stroke, and valvular heart disease. While the occurrence of cardiotoxicity is known for many older cancer therapies, it needs to be largely evaluated for newer forms of therapy. Diagnosing possible cardiotoxic side effects is essential for optimal treatment, but remains a challenge. Troponin and the natriuretic peptides play an essential role as cardiac biomarkers in the diagnosis of conventional heart diseases. However, they also appear to play an important role in the detection of cardiotoxicity, as well as in the treatment of cardio-oncology patients. Elevated troponin or B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are associated with increased overall mortality and were associated with the development of heart failure in selected cohorts. Troponin can also be used to identify myocarditis associated with immune checkpoint inhibitor therapy. This overview summarizes the current knowledge about biomarkers for the detection of cardiotoxicity due to tumor therapy. Possible clinical recommendations for the detection of cardiotoxic effects using biomarkers are also outlined.

Establishing an oncocardiology service.

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.

Red blood cell transfusion in patients with ST-elevation myocardial infarction-a meta-analysis of more than 21,000 patients.

BACKGROUND: Red blood cell transfusion remains controversial in patients with acute coronary syndromes and particularly in patients with ST-elevation myocardial infarction (STEMI). METHODS: We systematically searched PubMed, Cochrane, EMBASE, and Web of Science for studies published until January 2017 describing the outcomes in patients with STEMI who received red blood cell transfusion, compared with patients who did not. RESULTS: A total of 21,770 patients with STEMI from 5 cohort studies were included in the meta-analysis, 984 (4.5%) received red blood cell transfusion and 20,786 (95.4%) did not. Red blood cell transfusion was associated with a higher risk of in-hospital and long-term mortality, emergency repeated percutaneous coronary intervention (PCI), reinfarction rate, stroke rate, and heart failure. The group with red blood cell transfusion had a slightly higher incidence of diabetes mellitus and hypertension, but a lower incidence of smoking. The two groups had the same incidence of prior myocardial infarction, prior coronary artery bypass graft surgery and malignancy. Prior heart failure, prior stroke and prior PCI were more frequent in the group that had received red blood cell transfusion. The mean nadir haemoglobin was 8.5 ± 0.1 g/dl in the group with red blood cell transfusion and 12.5 ± 0.4 g/dl in the control group, p < 0.001. CONCLUSIONS: Red blood cell transfusion increases the morbidity and mortality in patients with STEMI. This difference could not be explained by the higher morbidity in the red blood cell transfusion group alone. Further randomised controlled trials are required to provide a reliable haemoglobin threshold for these patients.

Imaging for planning of transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) has proven to be the standard of care for patients with prohibitive and high operative risk; today, it is considered a reasonable alternative to surgical aortic valve replacement in intermediate-risk patients. As indications for TAVI move toward patients at lower risk, safety aspects are becoming even more important. Furthermore, adequate patient selection is key for predictable procedural success with minimal complications, translating into an optimal clinical outcome. Decisions on valve type and size as well as on the access route are based on multimodality imaging including echocardiography, multislice computed tomography, and cardiac catheterization with peripheral angiography. This combination of multiple imaging modalities provides the best picture of a patient's anatomical and physiological suitability for the TAVI procedure. Yet, the reliability of preprocedural imaging is influenced by the quality of the images, which should be as high as possible, and both image acquisition and interpretation should be performed in a standardized manner. This article provides a concise overview of standardized multimodality imaging for the preprocedural planning and assessment of patients undergoing TAVI.

Achromatic nulling interferometer based on a geometric spin-redirection phase.

Nulling interferometry aims to perform destructive interference achromatically. It is used to detect a faint source near a bright one and to provide dark field, an annular pupil, and rotational shear. A nulling out-of-plane interferometer that utilizes the geometric phase of spin redirection is proposed. The degree of nulling is determined by beam collimation and angular orientation of mirrors. Simulations and experiments are in reasonable agreement.

Edge localization of subwavelength structures by use of polarization interferometry and extreme-value criteria.

A polarization interferometric method is presented for the quantitative microscopy of topographical structures with subwavelength linewidths. A liquid-crystal phase shifter is inserted into the imaging optics of a reflected-light microscope, and the principles of phase-shifting interferometry are applied to measuring the phase and the contrast of the TE-polarized image (E parallel edge) with the TM-polarized image (E perpendicular edge) as the reference. This common-path interferometric method provides selective edge detection for line structures because the polarization difference is localized at the structure edges. Two different threshold criteria for linewidth determination are discussed: distance of the contrast minima and distance of the points of the steepest phase change. Linewidths as small as 300 nm were measured at a 635-nm wavelength. The dependence on the illumination numerical aperture, as well as on the material, the width, and the depth of the structure, is investigated both experimentally and by rigorous numerical simulations.

Phase-shifting polarization interferometry for microstructure linewidth measurement.

We report on a novel procedure to measure the linewidth of steep microstructures, based on the polarization anisotropy caused by the structure edges. A liquid-crystal phase shifter and a polarizer are introduced into the imaging optics of a reflection-mode microscope. We apply the principle of phase-shifting interferometry to measure the phase and contrast of a TM-polarized image with the TE-polarized image as reference. The method provides selective edge detection because the polarization difference is localized at the structure edges.

Structure determination of weak phase objects from interferometric near-field measurements.

Amplitude and phase of diffraction near fields behind two-dimensional weak phase objects (n ≍ 1.02 + iO.0002) are measured with electromagnetic 3-cm waves in TM and TE polarization. Dielectric slabs and strips with a trapezoidal or rectangular cross section are considered (width 1.5λ-36.0λ; thickness 0.6λ-2.4λ; wedge angle 30°-150°). For numerical simulation of the measured fields, a modification of the first Born approximation for weak scatterers is developed, which yields a remarkably better agreement with the measurements but requires no higher numerical efforts than the first Born approximation. Procedures for the determination of width, thickness, and wedge angle of the objects from measured diffraction fields are presented.

Polarization- and thickness-dependent near fields of small phase-shifting structures.

The spatial distribution of amplitude and phase in the diffraction near field behind phase-shifting structures of infinite length and small rectangular cross section (