PET/CT-identified atrial hypermetabolism is an index of atrial inflammation in patients with atrial fibrillation.

BACKGROUND: Although atrial inflammation has been implicated in the pathophysiology of atrial fibrillation (AF), the identification of atrial inflammation remains challenging. We aimed to establish a positron emission tomography/computed tomography (PET/CT) protocol with 18Fluor-labeled fluorodeoxyglucose (18F-FDG) for the detection of atrial hypermetabolism as surrogate for inflammation in AF. METHODS: We included n = 75 AF and n = 75 non-AF patients undergoing three common PET/CT protocols (n = 25 per group) optimized for the detection of (a) inflammation and (b) malignancy in predefined fasting protocols, and (c) cardiac viability allowing for maximized glucose uptake. 18F-FDG-uptake was analyzed in predefined loci. RESULTS: Differences of visual atrial uptake in AF vs non-AF patients were observed in fasting (inflammation [13/25 vs 0/25] and malignancy [10/25 vs 0/25]) protocols while viability protocols showed non-specific uptake in both the groups. In the inflammation protocol, AF patients showed higher uptake in the right atrium [(SUVmax: 2.5 ± .7 vs 2.0 ± .7, P = .01), atrial appendage (SUVmax: 2.4 ± .7 vs 2.0 ± .6, P = .03), and epicardial adipose tissue (SUVmax: 1.4 ± .5 vs 1.1 ± .4, P = .04)]. Malignancy and viability protocols failed to differentiate between AF and non-AF. CONCLUSION: Glucose uptake suppression protocols appear suitable in detecting differential atrial 18F-FDG uptake between AF and non-AF patients. Imaging-based assessment of inflammation might help to stratify AF patients offering individualized therapeutic approaches.

Role of catheter location on local impedance measurements and clinical outcome with the new direct sense technology in cardiac ablation procedures.

Background: A novel catheter technology (direct sense, DS) enables periprocedural local impedance (LI) measurement for estimation of tissue contact during radiofrequency ablation (RFA) for real-time assessment of lesion generation. This measure reflects specific local myocardial conduction properties in contrast to the established global impedance (GI) using a neutral body electrode. Our study aimed to assess representative LI values for the cardiac chambers, to evaluate LI drop in response to RF delivery and to compare those values to established GI measures in patients undergoing RFA procedures. Methods and Results: Seventy-three patients undergoing RFA with the DS technology were included. Within the cardiac chambers, baseline LI was significantly different, with the highest values in the left atrium (LA 107.5 ± 14.3 Ω; RV 104.6 Ω ± 12.9 Ω; LV 100.7 Ω ± 11.7 Ω, and RA 100.5 Ω ± 13.4 Ω). Baseline LI was positively correlated to the corresponding LI drop during RF delivery (R2 = 0.26, p = 0.01) representing a promising surrogate of lesion generation. The observed mean LI drop (15.6 ± 9.5 Ω) was threefold higher as GI drop (4.9 ± 7.4 Ω), p < 0.01. We evaluated the clinical outcome in a subgroup of patients undergoing DS-guided pulmonary vein isolation, which was comparable regarding arrhythmia recurrence to a conventional ablation cohort (57 % vs 50 %, p = 0.2). Conclusion: We provide detailed information on LI measures in electrophysiological procedures with significant differences within the cardiac chambers highlighting that RFA-related LI drop can serve as a promising surrogate for real-time assessment of lesion generation. Guiding the electrophysiologist in RFA procedures, this additional information promises to improve safety profile and success rates in the interventional treatment of arrhythmias.

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.

[What actually happens in hybrid imaging?] / Was passiert eigentlich in der Hybridbildgebung?

CLINICAL/METHODOLOGICAL ISSUE: The goal of this article is to shed light on innovations in perfusion imaging and the fields of application that have opened up in hybrid imaging of the heart. STANDARD RADIOLOGICAL METHODS: As before, the most commonly used modalities in hybrid imaging are single photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT). Perfusion tracers and the radioactively labeled glucose analog 18F­fluorodeoxyglucose (FDG) are commonly used for vitality imaging. METHODICAL INNOVATIONS: Use of PET/MRI (magnetic resonance imaging) is becoming increasingly widespread. In addition, FDG is also increasingly applied in imaging infectious and inflammatory myocardial diseases. Furthermore, novel tracers are used, such as the amyloid-specific tracers in cardiac amyloidosis. PERFORMANCE: Overall, this development has led to an increasing use of hybrid imaging techniques. These still include myocardial perfusion imaging, but are also used in inflammatory and infectious diseases such as endocarditis, myocarditis and sarcoidosis, as well as in underestimated diseases such as cardiac amyloidosis. The use of tracers has led to the creation of new fields of application in hybrid imaging. PRACTICAL RECOMMENDATIONS: Hybrid imaging combining myocardial perfusion and coronary visualization seems to be particularly advantageous in complex cases such as multivessel disease. In infectious and inflammatory myocardial diseases, FDG PET/CT or PET/MRI has clearly demonstrated its added value. New fields of application are very promising, but their significance has yet to be clearly demonstrated.

[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.

Critical inflammatory mechanisms underlying arrhythmias.

During the past few decades, cardiovascular research has increasingly focused on systemic inflammatory mechanisms, particularly in the field of atherosclerosis but also in association with cardiac arrhythmogenesis. Objective inflammatory markers including C­reactive protein and cytokines, also called "biomarkers," seem to serve as predictors of onset and prognosis of cardiac arrhythmias. This review gives an overview of potential mechanisms underlying inflammatory processes and arrhythmias, especially atrial fibrillation, which is the most common sustained arrhythmia in daily clinical routine. The association between inflammatory pathways and cardiac arrhythmia is highly complex and includes direct as well as indirect pathways. While past research into arrhythmia focused on fibrosis, altered action potential properties, and ischemia, novel concepts include coagulation and inflammation in cardiac tissue. The underlying mechanisms are altered electrophysiological properties, including ion channel disturbance, early and late afterdepolarizations, as well as enhanced fibrosis and structural remodeling in cardiomyopathies. These pathophysiological factors favor the occurrence of ectopic pacemakers as well as re-entry tachycardia. Further studies are essential to better understand the main inflammatory signal cascades and the exact proarrhythmic effect of interacting key mediators. This will facilitate the evaluation of future anti-inflammatory therapeutic approaches for arrhythmias, analogous to recent developments in atherosclerosis.

Cardiac PET/MRI-an update.

It is now about 8 years since the first whole-body integrated PET/MRI has been installed. First, reports on technical characteristics and system performance were published. Early after, reports on the first use of PET/MRI in oncological patients were released. Interestingly, the first article on the application in cardiology was a review article, which was published before the first original article was put out. Since then, researchers have gained a lot experience with the PET/MRI in various cardiovascular diseases and an increasing number on auspicious indications is appearing. In this review article, we give an overview on technical updates within these last years with potential impact on cardiac imaging and summarize those scenarios where PET/MRI plays a pivotal role in cardiovascular medicine.

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.

Impact of anticoagulation and vasoactive medication on regained radial artery patency after catheterization: a case-control study.

BACKGROUND: Radial artery access is the primary approach for coronary interventions due to higher safety profile in comparison to femoral access. Radial artery occlusion (RAO) is the main complication of transradial catheterization that can lead to severe symptoms and a permanent artery occlusion. The incidence of RAO after transradial access ranges from 5 to 38% and data regarding treatment is scarce. Whether anticoagulation and vasoactive medication provides an additional benefit in recovery of radial artery patency (RAP) after catheterization has not been investigated in detail. AIM: The objective was to investigate the impact of anticoagulation and vasoactive medication on regained patency after documented RAO following transradial catheterization. PATIENTS AND METHODS: Overall 2635 patients were screened. 2215 (84%) catheterizations were performed by femoral and 420 (16%) by radial access. In 30 patients RAO was observed. In case of RAO patients were classified in three groups: Anticoagulation, anticoagulation added with alprostadil and controls. Follow-up was conducted after 3 months with ultrasound and clinical examination. RESULTS: Eight patients received anticoagulation and 11 patients anticoagulation together with alprostadil. Eleven patients served as controls. Recovery of RAP after catheterization was higher following either treatment (79.5%) compared to controls (0%, p = 0.006). Subgroup analysis yielded a higher RAP recovery in patients treated with anticoagulation (62.5%) as compared to controls (0%, p = 0.002). No effect on regained RAP was found with additional alprostadil therapy (33.3%) compared to anticoagulation therapy (62.5%, p = 0.229). CONCLUSION: RAO should be treated with anticoagulation to regain patency. Addition of vasoactive medication does not lead to further beneficial effects. Further research is needed regarding preventive and therapeutic strategies following RAO.

Nationwide but still inhomogeneous distribution of certified chest pain units across Germany : Need to strengthen rural regions.

AIM: The purpose of this work was to analyze structure, distribution, and bed capacities of certified German chest pain units (CPUs) to unveil potential gaps despite nationwide certification of 230 units till the end of 2015. METHODS: Analysis of number and structure of CPUs per state, resident count, and population density by standardized telephone interview, online research, and data collection from the registry of the Federal Statistical Office for all certified German CPUs. RESULTS: Nationwide, German health facilities provided a mean of 1 CPU bed within a certified unit per 65,000 inhabitants. Bremen, Hamburg, Hesse, and Rhineland-Palatinate provided more than 1 bed per 50,000 inhabitants. Most CPUs (49%) were located in the emergency room. All university hospitals in Germany provided a certified CPU. Most units were found in academic teaching hospitals (146 CPUs). Only 42 CPUs were found in nonacademic providers of primary health care. CONCLUSION: The absolute necessary number of CPUs to reach full nationwide coverage is still unknown. The current analysis shows a high number of CPUs and bed capacities within the cities and industrial areas without relevant gaps, but also demonstrates a certain undersupply in more rural areas as well as in some of the former eastern federal states of Germany.

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.

Safety and efficacy of transseptal puncture guided by real-time fusion of echocardiography and fluoroscopy.

AIMS: Visual guidance through echocardiography and fluoroscopy is crucial for a successful transseptal puncture (TSP) in a prespecified region of the fossa ovalis. The novel EchoNavigator system Release II (EchoNav II, Philips Healthcare, Andover, Massachusetts, USA) enables the real-time fusion of fluoroscopic and echocardiographic images. We evaluated this new imaging method in respect to safety and efficacy of TSP during MitraClip implantation and left atrial appendage closure. METHODS: Forty-four patients before (-EchoNav) and 44 patients after (+EchoNav) the introduction of real-time fusion were included in our retrospective, single-centre study. The primary endpoint was the occurrence of adverse events due to TSP. Secondary endpoints were successful puncture at the prespecified region and time until TSP (min). RESULTS: In both groups TSP was performed successfully in the prespecified region and no adverse events occurred during or due to the accomplishment of TSP. Time until TSP was significantly reduced in the +EchoNav group in comparison with the EchoNav group (18.48 ± 5.62 min vs. 23.20 ± 9.61 min, p = 0.006). CONCLUSIONS: Real-time fusion of echocardiography and fluoroscopy proved to be as safe and successful as standard best practice for TSP. Moreover, efficacy was improved through significant reduction of time until TSP.

On- versus off-hour care for patients with non-ST-segment elevation myocardial infarction in Germany : Exemplary results within the chest pain unit concept.

AIM: The aim of this study was to analyze differences in the timing of invasive management of patients with high-risk acute coronary syndrome without persistent ST-segment elevation (hr-NSTE-ACS) or myocardial infarction without persistent ST-segment elevation (NSTEMI) between on- and off-hours in a German chest pain unit (CPU). PATIENTS AND METHODS: We retrospectively enrolled 160 NSTEMI patients in the study, who were admitted to two German CPUs in 2013. Patients presenting on weekdays between 8 a.m. and 6 p.m. were compared with patients presenting during off-hours. Data analysis included time intervals from admission to invasive management (goals: for hr-NSTE-ACS, <2 h; for NSTEMI, <24 h) and the resulting guideline adherence. RESULTS: Guideline-adherent timing of an invasive strategy did not differ significantly between the on-hour (6.5 h [3.0-22.0 h], 79.9 %) and off-hour groups (10.5 h [2.0-20.0 h], 75.3 %; p = 0.94), without additional significant differences between admissions during off-hours Monday to Thursday and weekends (10.0 h [2.0-19.0 h], 75.6 % vs. 7.5 h [2.0-20.0 h], 76.2 %; p = 0.96). CONCLUSION: Our exemplary experience in two different German CPUs demonstrates adequate timing of coronary catheterization in over 75 % of cases, irrespective of admission during on- or off-hours. Nationwide validation of our findings by the German CPU registry is mandatory.

[New strategies in cardioprotection during acute myocardial infarction: Impact of hypoxic nitrate-nitrite-NO signaling]. / Neue Strategien in der Kardioprotektion beim akuten Myokardinfarkt: Bedeutung des hypoxischen Nitrat-Nitrit-NO-Stoffwechsels.

Acute myocardial infarction remains one of the leading causes of morbidity, mortality and disability in industrialized countries. After an acute myocardial infarction, early and successful myocardial reperfusion is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. The process of restoring blood flow to the ischemic myocardium, however, can induce injury itself. This phenomenon, termed myocardial ischemia reperfusion injury (IRS), can paradoxically reduce the beneficial effects of myocardial reperfusion. In experimental studies a number of strategies have been shown to ameliorate lethal reperfusion injury. However, the translation of these beneficial effects into the clinical setting has been disappointing. Modulation of the hypoxic nitrate-nitrite-nitric oxide (NO) pathway may have the potential to challenge this problem. First translational studies are promising and clinical trials are ongoing.

Vagal heart rate control in patients with atrial fibrillation: impact of tonic activation of peripheral chemosensory function in heart failure.

Heart failure (HF) and atrial fibrillation (AF), emerging as two epidemics of the twenty-first century, are commonly associated with each other. Both have been mechanistically linked to changes in cardiac vagal control. The importance of peripheral chemosensors, located in the carotid body, has not been elucidated so far. We therefore investigated whether tonic activation of excitatory chemoreceptor afferents contributes to the altered vagal control in HF patients with a history of AF. In 18 patients (72 ±9 year, 7 male) with sinus rhythm and a history of AF (n=9, without any evidence of structural heart disease, AF group; n=9 with structural heart disease and clinical presentation of HF, AFHF group) we investigated the impact of chemosensory deactivation (by breathing 100% oxygen) on heart rate, blood pressure, cardiac output, total peripheral resistance, oxygen saturation and breathing rate. Ten healthy individuals served as a control group. In addition, we performed a deep breathing test demonstrating an impaired heart rate variation in patients with and without HF as compared with controls (expiration/inspiration difference: 23.9±6.9 vs. 6.9±6.1 bpm, and 23.9±6.9 vs. 7.8±4.8 bpm; p<0.05). In both control and AF groups, heart rate decreased during chemoreceptor deactivation (control: -4.8±3.4%; AF: -5.1±3.0%; p<0.05), whereas heart rate did not change in AFHF patients. This resulted in impaired cardiac chemoreflex sensitivity in AFHF patients (1.9±1.6 vs. 0.5±1.2 ms/mmHg; p<0.05). In conclusion, our data suggest that tonic activation of excitatory chemoreceptor afferents contributes to a low vagal tone in heart failure patients with a history of AF (Clinical Trials NCT01262508).