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Reduced systolic and diastolic calcium levels in cardiomyocytes from NKA-α2 transgenic mice minimize the desensitization of the β-adrenergic signaling system. These effects result in an improved β-adrenergic reserve and prevent functional deterioration and cardiac remodeling.

Diese Stellungnahme der Deutschen Gesellschaft fur Kardiologie fasst Informationen und Empfehlungen zum Umgang mit nicht-aktiven (auch genannt „passiven“) kardiovaskularen Implantaten (z. B. Koronarstents) bei der Magnetresonanztomographie (MRT) zusammen. Es wird empfohlen, bei jedem Patienten vor einer MRT-Untersuchung das Vorhandensein von nicht-aktiven kardiovaskularen Implantaten zu erfragen, gegebenenfalls detaillierte Implantat-Informationen einzuholen und schlieslich unter individueller Nutzen-Risiko-Abwagung die Entscheidung fur oder gegen die MRT-Untersuchung zu treffen. Bei der MRT-Untersuchung sind gegebenenfalls Anpassungen der technischen MRT-Parameter oder des Untersuchungsablaufs zu berucksichtigen. Diese Aufgaben obliegen dem die MRT-Untersuchung durchfuhrenden Arzt. Er wird unterstutzt, indem der Patient selbst sowie der uberweisende Arzt die notwendigen Informationen rechtzeitig zur Verfugung stellen. Dabei ist die Verwendung von Implantatpassen und Implantatdatenbanken hilfreich. Werden diese Vorsichtsmasnahmen berucksichtigt, sind nach derzeitigem Kenntnisstand MRT-Untersuchungen bei Patienten mit nicht-aktiven kardiovaskularen Implantaten im Allgemeinen ohne gravierende Sicherheitsbedenken durchfuhrbar.

Since its beginning, 30 years ago, magnetic resonance imaging of the heart made tremendous progress. Starting from an almost experimental level in the 90 s it has now become a routine tool within cardiac diagnostics. This article presents a selection of present applications of cardiac magnetic resonance imaging. Besides it superiority in determining mass and volumes of the heart, structural imaging of myocardial tissue has become the domain of cardiac magnetic resonance imaging. This implies detection and quantification of scars and fibrosis, inflammatory and infiltrative processes in myocarditis and amyloidosis, and characterization of cardiac tumors. Perfusion imaging allows detection of ischemia, and measurement of blood flow quantifies cardiac shunts and valve disorders. In combination with Positron Emission Tomography, the relationship of molecular/cellular processes and functional, microstructural alterations become visible in myocarditis and amyloidosis. Recent contraindications of cMRI/MRI as cardiac devices MRI have been resolved; however, image quality of the heart is still a challenge.

Magnetic resonance imaging (MRI) has long been contraindicated in patients with implanted pacemakers, defibrillators, and cardiac resynchronisation therapy (CRT) devices due to the risk of adverse effects through electromagnetic interference. Since many recipients of these devices will have a lifetime indication for an MRI scan, the implantable systems should be developed as ‘MRI-conditional’ (be safe for the MRI environment under predefined conditions). We evaluated the clinical safety of several Biotronik ProMRI (‘MRI-conditional’) defibrillator and CRT systems during head and lower lumbar MRI scans at 1.5 Tesla. The study enrolled 194 patients at 22 sites in Australia, Canada, and Europe. At ≥9 weeks after device implantation, predefined, non-diagnostic, specific absorption rate (SAR)-intensive head and lower lumbar MRI scans (total ≈30 minutes per patient) were performed in 146 patients that fulfilled pre-procedure criteria. Three primary endpoints were evaluated: freedom from serious adverse device effects (SADEs) related to MRI and defibrillator/CRT (leading to death, hospitalisation, life-threatening condition, or potentially requiring implanted system revision or replacement), pacing threshold increase, and sensing amplitude decrease, all at the 1-month post-MRI clinical visit. No MRI-related SADE occurred. Lead values remained stable, measured in clinic and monitored daily by the manufacturer home monitoring technology.

In der vorliegenden Stellungnahme der Deutschen Gesellschaft fur Kardiologie (DGK) in Zusammenarbeit mit der Deutschen Gesellschaft fur Arbeits- und Umweltmedizin (DGAUM) werden elektromagnetische Interferenzen bei elektrisch aktiven kardialen Implantaten diskutiert, die vorhandene Literatur zusammengefasst und, soweit moglich, bewertet. Aufgrund der zunehmenden Technisierung des Alltags und des beruflichen Umfelds mit immer mehr elektrischen oder elektronischen Geraten erlangt das Thema zunehmende Relevanz. Dies wird begleitet von Weiterentwicklungen der bestehenden transvenosen Implantate sowie neuen Aggregattechnologien wie kabellosen Schrittmachern und total subkutanen implantierbaren Kardioverter-Defibrillatoren. Die Konfiguration von elektromagnetischen Feldern (EMF) kann bezogen auf Frequenz und Feldstarke stark variieren und ruft im Korper und somit am Aggregat ganz unterschiedliche Reaktionen hervor. Der physikalische Hintergrund der Wirkung von EMF auf Korper und Implantat wird allgemein verstandlich dargestellt. Verschiedene Storszenarien werden auch in Bezug auf die Grunderkrankung erlautert. Aus interdisziplinarer Perspektive werden Aspekte einer Exposition mit EMF sowohl im Alltag als auch im beruflichen Umfeld beleuchtet. Der primaren Implantatversorgung EMF-exponierter Patienten, der Risikobewertung im arbeitsmedizinischen Kontext und der Gerateprogrammierung mit Troubleshooting kommt hierbei besondere Bedeutung zu. Zudem werden konkrete Vorgehensweisen fur Arbeitsmediziner in Betrieben an die Hand gegeben, um den Wiedereingliederungsprozess zu unterstutzen. Im Rahmen dessen erfolgt auch eine kurze Darstellung der aktuellen Gesetzeslage. Uberdies soll das Dokument motivieren, Studien aufzulegen, die das Thema der elektromagnetischen Interferenz in vivo fur aktuelle Aggregatgenerationen sowie Neuentwicklungen systematisch untersuchen, sodass eine suffiziente Risikobewertung fur verschiedene Frequenzbereiche und damit technische Gerate erfolgen kann.

Background Cardiac arrhythmias are a serious complication in patients admitted due to intoxication in suicidal attempts. Upon admission, detailed information about the specific kind of intoxication are frequently missing. The differential diagnoses of electrocardiogram (ECG) changes such as elevation of T-waves, prolongation of the QT-interval or elevation of ST-segments in this special subgroup of patients comprise drug-induced electrolyte disorders or direct toxic effects on cardiac excitation and repolarization. Case summary In this clinical report of a 27-year-old male patient, we present a case of unusual ECG alterations mimicking ST-elevation, high amplitude, biphasic T-waves and prolongation of QT-interval. These changes of surface ECG were induced by ingestion of cylindrical batteries in a suicidal attempt and immediately normalized after removal of batteries by esophagogastroduodenoscopy. Discussion There is limited literature describing changes in surface ECG in patients having ingested cylindrical batteries. We propose two hypotheses for the occurrence of these changes after ingestion of cylindrical batteries: (i) Cardiac movement within the perturbation field induced by the batteries causes electrical changes on a time scale of the heart rate which are above the threshold of the high pass filter. (ii) The batteries’ electrotonic potential affects the membrane currents of cardiac myocytes, not inducing an action potential but generating repolarization abnormalities. Individual factors, such as body constitution and localization of the batteries within the stomach, determine the interindividual characteristics of repolarization abnormalities.

Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance of 18F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed. Twenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwent 18F-florbetaben-PET/CT for diagnostic work-up. Qualitative and quantitative assessment including calculation of myocardial tracer retention (MTR) was performed, and compared to echo (n = 20), CMR (n = 16), scintigraphy (n = 16) and serologic biomarkers (NT-proBNP, cTnT, free light chains). In four patients, follow-up PET/CT was available (after treatment initiation, n = 3; surveillance, n = 1). PET demonstrated myocardial 18F-florbetaben retention consistent with CA in 14/22 patients. Suspicion of CA was subsequently dropped in all eight PET-negative patients. Amyloid subtypes showed characteristic retention patterns (AL > AA > ATTR; all p 0.47|, all p

In dieser Empfehlung der Deutschen Gesellschaft fur Kardiologie (DGK) werden die besonderen Aspekte von kardialen Magnetresonanztomographie(MRT)-Untersuchungen bei Patienten mit Herzschrittmachern (HSM) und implantierbaren Kardioverter-Defibrillatoren (ICD) dargestellt. Es ist eine Erganzung/Aktualisierung zu dem Konsensuspapier der DGK und der Deutschen Rontgengesellschaft aus dem Jahr 2017 uber MRT-Untersuchungen bei Patienten mit HSM und ICD. Fokussiert auf kardiale MRT-Untersuchungen, werden physikalische und elektrophysiologische Erklarungen, hilfreich fur Verstandnis und Handhabung versierter Anwender, sowie Handlungsempfehlungen bezuglich Fragestellung und Patientenauswahl, Gerateprogrammierung, Monitoring und Modifikation der MRT-Sequenzen gegeben. Ziel ist es, Patienten mit aktiven kardialen Implantaten den Zugang zu einer kardialen MRT-Untersuchung unter strenger Indikationsprufung zu ermoglichen, ohne relevante Einschrankungen in Patientensicherheit und Bildqualitat einzugehen. Kernaussagen dieser Empfehlungen sind: 1. In Analogie zu sonstigen MRT-Untersuchungen sind konventionelle (d. h. nicht bedingt MRT-sichere) HSM- und ICD-Systeme auch fur kardiale MRT-Untersuchungen nicht mehr als eine absolute, sondern als eine relative Kontraindikation anzusehen. 2. Kardiale MRT-Untersuchungen bei Patienten mit HSM oder ICD sind jedoch mit einem besonderen Risiko verbunden, da sich einerseits das Gerat in der Bildgebungsregion befindet und dadurch Wechselwirkungen zwischen Gerat, MRT und Gewebe verstarkt sein konnen, und andererseits das Myokard der untersuchten Patienten potenziell vulnerabel und daher moglicherweise anfallig fur Storeinflusse ist. 3. Neben Sicherheitsaspekten kann die Bildqualitat durch einen HSM oder ICD beeintrachtigt werden, sodass angepasste MRT-Pulssequenzen erforderlich sein konnen. 4. Entscheidend bei Indikationsstellung und Untersuchungsdurchfuhrung sind die Abschatzung des individuellen Nutzen-Risiko-Verhaltnisses, eine umfassende Aufklarung uber spezifische Risiken, dezidierte HSM-/ICD-bezogene und MRT-bezogene Sicherheitsmasnahmen zur Reduzierung dieser Risiken sowie adaquate Monitoringtechniken wahrend der MRT-Untersuchung. Diese Komplexitat erfordert die Anwesenheit von in kardialer MRT und ICD/HSM-Therapie erfahrenem arztlichen Personal. 5. Wenn auch einige HSM und ICD als bedingt MRT-sicher („MR conditional“) einschlieslich kardialer MRT-Untersuchungen zugelassen sind, gelten dennoch weitgehend ahnliche Vorsichts- und Monitoringmasnahmen wie bei Tragern konventioneller HSM- und ICD-Systeme. Fur die Patientensicherheit sind die genaue Kenntnis und Beachtung der spezifischen Nutzungsbedingungen des jeweiligen HSM oder ICD entscheidend.

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE-/- mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. All in vivo MR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based “Flow Tool”. The body weight of ApoE-/- mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE\(^{-/-}\)mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. Allin vivoMR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE\(^{-/-}\)mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II–restricted epitopes, we found that myosin heavy chain α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA 614–629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence that MI context induces prohealing T cell autoimmunity in mice and confirm the existence of an analogous heart/med-LN/T cell axis in patients with MI.

Contrast and non-contrast MRI based characterization of myocardium by T 1 -mapping will be of paramount importance to obtain biomarkers, e.g. fibrosis, which determines the risk of heart failure patients. T 1 -mapping by the standard post-processing of the modified look-locker inversion recovery (MOLLI) lacks of accuracy when trying to reduce its duration, which on the other hand, is highly desirable in patients with heart failure. The recently suggested inversion group fitting (IGF) technique, which considers more parameters for fitting, has a superior accuracy for long T 1 times despite a shorter duration. However, for short T 1 values, the standard method has a superior precision. A conditional fitting routine is proposed which ideally takes advantage of both algorithms. Materials and methods All measurements were performed on a 1.5 T clinical scanner (ACHIEVA, Philips Healthcare, The Netherlands) using a MOLLI 5( n )3( n )3 prototype with n (heart beats) being a variable waiting time between inversion experiments. Phantom experiments covered a broad range of T 1 times, waiting times and heart rates. A saturation recovery experiment served as a gold standard for T 1 measurement. All data were analyzed with the standard MOLLI, the IGF fit and the conditional fitting routine and the obtained T 1 values were compared with the gold standard. In vivo measurements were performed in a healthy volunteer and a total of 34 patients with normal findings, dilative cardiomyopathy and amyloidosis. Results Theoretical analysis and phantom experiments provided a threshold value for an apparent IGF T 1 * determining processing with IGF post processing for values above, or switching to the standard technique for values below. This was validated in phantoms and patients measurements. A reduction of the waiting time to 1 instead of 3 heart beats between the inversion experiments showed reliable results. The acquisition time was reduced from 17 to 13 heart beats. The in vivo measurements showed ECV values between 25% (18–33%; SD 0.03) in the healthy, 30% (22–40%; SD 0.04) in patients with DCM and 45% (30–60%; SD 0.9) in patients with amyloidosis. Conclusion The adopted post-processing algorithm determines long T 1 values with high accuracy and short T 1 values while maintaining a high precision. Based on reduction of waiting time, and independence of heart rate, it shortens breath hold duration and allows fast T 1 -mapping, which is frequently a prerequisite in patients with cardiac diseases.

Purpose The importance of the orientation of the selective inversion slice in relation to the anatomy in flow-sensitive alternating inversion recovery arterial spin labeling (FAIR ASL) kidney perfusion measurements is demonstrated by comparing the standard FAIR scheme to a scheme with an improved slice selective control experiment. Methods A FAIR ASL method is used. The selective inversion preparation slice is set perpendicular to the measurement slice to decrease the unintended labeling of arterial spins in the control experiment. A T 1 * -based quantification method compensates for the effects of the imperfect inversion on the edge of the selective inversion slice. The quantified perfusion values are compared to the standard experiment with parallel orientation of imaging and selective inversion slice. Results Perfusion maps acquired with the perpendicular inversion slice orientation show higher sensitivity compared to the parallel orientation. The T 1 * -based quantification method removes artifacts arising from imperfect inversion slice profiles. The stability is improved. Conclusion Adjusting the labeling technique to the anatomy is of high importance. Improved sensitivity and reproducibility could be demonstrated. The proposed method provides a solution to the problem of FAIR ASL measurements of renal perfusion in coronal view.

This joint consensus paper of the German Roentgen Society and the German Cardiac Society provides physical and electrophysiological background information and specific recommendations for the procedural management of patients with cardiac pacemakers (PM) and implantable cardioverter defibrillators (ICD) undergoing magnetic resonance (MR) imaging. The paper outlines the responsibilities of radiologists and cardiologists regarding patient education, indications, and monitoring with modification of MR sequences and PM/ICD reprogramming strategies being discussed in particular. The aim is to optimize patient safety and to improve legal clarity in order to facilitate the access of SM/ICD patients to MR imaging. Key Points: Citation Format

Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance ofTwenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwentPET demonstrated myocardialImaging of cardiac amyloidosis (CA) with

PURPOSE An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs. METHODS A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference. RESULTS Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference. CONCLUSION The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Background Acute myocarditis as well as post-ischemic myocardial inflammation are generally associated with a profound activation of the immune system. Current established imaging techniques such as cardiac MRI reliably demonstrate signs of acute myocardial injury. However, detection of mediating cells such as macrophages is currently limited to experimental settings. We aimed to investigate the feasibility of somatostatin receptor (SSTR) based positron emission tomography/computed tomography (PET/CT) for detecting inflammatory lesions in patients after acute myocardial infarction or acute peri-/myocarditis. Methods 12 patients with active peri-/myocarditis (n=6) or sub-acute myocardial infarction (n=6) underwent SSTR-PET/CT and cardiac MRI within 3–10days after onset of symptoms. The AHA 17-segment model of the left myocardium was used for visual localization of inflamed myocardium for both imaging modalities. Tracer uptake of infarcted/inflamed myocardium was assessed as mean and maximum standardized uptake value (SUV mean and SUV max ) and compared with both remote myocardium and left ventricular (LV) cavity. Results SSTR-PET/CT revealed areas with increased cardiac tracer uptake in all patients. In the 17-segment model, PET/CT yielded 55 and MRI 47 positive segments. Overall, concordance of the 2 modalities was 85.3% (174/204 segments analyzed). In 9.3% (19/204), more positive segments were identified by PET/CT, whereas in 5.4% (11/204), MRI detected more positive segments. Conclusions The imaging patterns of SSTR-directed radiotracers and MRI in vivo show a close spatial relation of macrophage concentration and structural changes. This suggests the possibility of a new potential biomarker that predicts cardiac remodeling and, hence, progression towards heart failure. Prospective trials are warranted.

Supplemental Digital Content is available in the text., Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping. Objective: To determine whether hyperpolarized MR using [1-13C]pyruvate can assess the local cardiac inflammatory response after MI. Methods and Results: We performed hyperpolarized [1-13C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1-13C]lactate signals. MI caused intense [1-13C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1-13C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1-13C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1-13C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)–treated rats at 3 months. Conclusions: Hyperpolarized MR using [1-13C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation.

AIMS Sodium intake has been linked to left ventricular hypertrophy independently of blood pressure, but the underlying mechanisms remain unclear. Primary hyperaldosteronism (PHA), a condition characterized by tissue sodium overload due to aldosterone excess, causes accelerated left ventricular hypertrophy compared to blood pressure matched patients with essential hypertension. We therefore hypothesized that the myocardium constitutes a novel site capable of sodium storage explaining the missing link between sodium and left ventricular hypertrophy. METHODS AND RESULTS Using 23Na magnetic resonance imaging, we investigated relative sodium signal intensities (rSSI) in the heart, calf muscle, and skin in 8 PHA patients (6 male, median age 55 years) and 12 normotensive healthy controls (HC) (8 male, median age 61 years). PHA patients had a higher mean systolic 24 h ambulatory blood pressure [152 (140; 163) vs. 125 (122; 130) mmHg, P

Patients receiving dual-chamber implantable cardioverter-defibrillator (DR-ICD) therapy are at risk of developing atrial arrhythmia because of the increased rate of ventricular pacing and the progression of heart failure. Remote monitoring (RM) may identify the patients at highest risk of adverse events such as atrial arrhythmias. A total of 283 patients with 91,632 remote transmissions during a 15-month follow-up (FU) period enrolled in the LION registry were analysed. The parameters retrieved included the pacing mode, lower rate limit, percentage of atrial (%AP) and ventricular pacing (%VP), and percentage of atrial arrhythmia burden (%AB). In 92.7% of patients, the devices were initially programmed in DDD(R) or DDI(R), with changes of the pacing mode in 19.3% only. The lower rate limit remained stable in 80.4% of patients. At the first transmission, 8.7% of patients suffered from RM-detected atrial arrhythmia, which reached 36% during FU. The %AP was not associated with increased AB (p = 0.67), but the %VP was different in patients developing RM-detected atrial arrhythmia (26.9% vs. 13.7%, p < 0.00001). The %VP increased in 105 patients (significance level of α = 0.05), and 11 patients crossed the border of 50% VP. The LION substudy supports the concept of using RM in a real-world DR-ICD population. Remote monitoring of DR-ICDs allows for the quantification of the course of the pacing parameters and AB. Based on these observations, device parameters can be adjusted and optimized.

C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α have been shown to be involved in the orchestration of post-infarct inflammation and its resolution in patients with acute myocardial infarction (AMI) [(1)][1]. Recently, pilot visualization of CXCR4-expression

The cardiac affection in systemic sarcoidosis often presents as functional impairment or rhythmic abnormalities and is of prognostic relevance. Due to the focal granulomatous changes, the detection of the sarcoid lesions can be challenging. Cardiac MRI allows for a unique non-invasive presentation of the cardiac structure, and detects these typical changes even in up to 30% of asymptomatic patients. Treatment options include immunosuppressive therapies such as systemic corticosteroids that suppress the inflammatory processes. In an unfiltered group of sarcoidosis patients, however, many of the patients will be or already had been on immunosuppressive therapy, often due to an extra-cardiac affection. The presented study examines the influence of the immunosuppressive therapy on the findings of the initial screening MRI. All included patients have been seen at the University of Wuerzburg’s Centre for Rare Diseases (ZESE). In the context of the diagnostic workup, a cardiac MRI (1.5 or 3.0 T) was performed including morphologic, functional, and contrast enhanced imaging as well as edema imaging. All data were analyzed retrospectively. 171 patients with an eventually biopsy proven systemic sarcoidosis were included in the analysis. At the time of the MRI imaging procedure 58% of these patients had never had an immunosuppressive therapy, 22% had had already received an immunosuppressive therapy and 19% were currently under treatment. 21% of all patients showed positive MRI findings (11% without therapy, 9.4% with a prior or ongoing therapy). Between these groups, statistically no differences in the detection of late enhancement, edema and wall motion abnormalities were detected. The data of the analyzed population showed that the MRI is a valuable screening tool for both acute and past myocardial affection in the management of patients with sarcoidosis regardless of their current or prior treatment.

Flow of particles of two different species through a narrow channel with solely two discrete spatial positions is analyzed with respect to the species' capability to cooperate or compete for transport. The origin of the latter arises from particle-channel and interparticle interactions within the channel, i.e., blocking the position of a particle, and its interaction with its neighbors in the channel. The variety of occupation options within the channel defines the state space. The transition dynamics within is considered as a continuous Markov process, which, in contrast to mean-field approaches, conserves explicitly spatial correlations. A strong repulsive interaction between particles of the same kind and a very attractive empty channel imply a strong entanglement of transport of both species. In the limiting case of perfect coupling, flows in state space are restricted to a cyclic subspace, where they become all equivalent in the steady state. In particular, this implies equal particle flows of the two species. Entanglement of transport implies that the species mutually exert entropic forces on each other. For parallel directed concentration gradients this implies that the species' ability to cooperate increases with the degree of entanglement. Thus, the gradient of one species reciprocally induces a higher flow of the other species when compared to that in its absence. The opposite holds for antiparallel gradients where species mutually hamper their transport. For a sufficient strong coupling, the species under the influence of the stronger concentration gradient drives the other against its gradient, i.e., the positive mixing entropy production of the driving species becomes the motor for the negative mixing entropy production of the driven one. The degree of effectiveness by which negative entropy production emerges at the cost of positive entropy production increases with the coupling strength. This becomes evident from location and connectivity of the sources of entropy production in state space.

To develop and validate a fast cardiac magnetic resonance imaging T1 mapping technique with high spatial resolution based on a radial inversion-recovery (IR) spoiled gradient-echo acquisition.Approval for the study was granted by the local institutional review board, and all subjects gave written informed consent. An electrocardiographically triggered radial single-shot IR (TRASSI) sequence was developed in conjunction with a custom-written fitting algorithm. The proposed imaging technique was validated in phantom measurements and then used for cardiac T1 mapping in 62 subjects with or without cardiac disease. The study population included 51 healthy subjects, three patients with arrhythmia, and eight patients with myocardial infarction. The potential heart rate dependency of the TRASSI method was tested by using linear regression analysis. Statistically significant differences between the sexes and various section orientations were analyzed with a Student t test for independent groups and a repeated-measures analysis of variance for dependent groups.High-spatial-resolution T1 maps (1.17 × 1.17 mm) without motion artifacts and without heart rate dependency (slope = -0.0303, R(2) = 0.0000887, P = .899) were acquired with an acquisition time of less than 6 seconds in all subjects. The mean T1 of healthy left ventricular myocardium across all examined subjects was 1031 msec ± 33 (standard deviation). Testing for reproducibility in three individuals with 34 repetitive measurements revealed a mean standard deviation of 4.1 msec (0.412%). Subacute and chronic myocardial infarction could be detected in all eight patients. T1 disturbances due to arrhythmia proved to be minimal in three patients (standard deviation,1.2%).Fast and accurate cardiac T1 mapping is feasible within a single-shot IR experiment.

Purpose A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice. Methods A flow-sensitive alternating inversion recovery arterial spin labeling method using an untriggered FLASH-read out with random sampling is used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism to reduce deviation from Look-Locker conditions are needed. Electrocardiogram and respiratory data are recorded for retrospective gating and triggering. A model-based technique is used to reconstruct missing k-space data to cope with the undersampling inherent in retrospectively gated methods. Acquisition and reconstruction were validated numerically and in phantom measurements before in vivo experimentation. Results Quantitative perfusion maps were acquired within a single slice measurement time of 11 min. Perfusion values are in good accordance to literature values. Myocardial infarction could be clearly visualized and results were confirmed with histological results. Conclusion The proposed method is capable of producing quantitative perfusion maps on arbitrary positions in the heart cycle within a short measurement time. The method is robust against irregular breathing patterns and heart rate changes and can be implemented on all scanners. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in living cells, we provide direct experimental evidence that the cAMP concentration in the vicinity of an individual PDE molecule is below the detection limit of our FRET sensors (

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE-/- and WT mice were determined for global and local PWV measurements (global PWV: ApoE-/-: 2.7±0.2m/s vs WT: 2.1±0.2m/s, P, PLoS ONE, 12 (2), ISSN:1932-6203

Quantitative nuclear magnetic resonance imaging (MRI) shifts more and more into the focus of clinical research. Especially determination of relaxation times without/and with contrast agents becomes the foundation of tissue characterization, e.g. in cardiac MRI for myocardial fibrosis. Techniques which assess longitudinal relaxation times rely on repetitive application of readout modules, which are interrupted by free relaxation periods, e.g. the Modified Look-Locker Inversion Recovery = MOLLI sequence. These discontinuous sequences reveal an apparent relaxation time, and, by techniques extrapolated from continuous readout sequences, the real T1 is determined. What is missing is a rigorous analysis of the dependence of the apparent relaxation time on its real partner, readout sequence parameters and biological parameters as heart rate. This is provided in this paper for the discontinuous balanced steady state free precession (bSSFP) and spoiled gradient echo readouts. It turns out that the apparente longitudinal relaxation rate is the time average of the relaxation rates during the readout module, and free relaxation period. Knowing the heart rate our results vice versa allow to determine the real T1 from its measured apparent partner., Comment: 1 Figure

In diesem gemeinsamen Konsensuspapier der Deutschen Rontgengesellschaft und der Deutschen Gesellschaft fur Kardiologie werden der MR-physikalische und elektrophysiologische Hintergrund sowie das prozedurale Management fur MR-Untersuchungen von Patienten mit Herzschrittmachern und implantierbaren Kardioverter-Defibrillatoren dargestellt. Es werden detaillierte Handlungsanweisungen bezuglich Indikationsstellung, den spezifischen Untersuchungsbedingungen mit Umprogrammierung des SM/ICD- Systems, Modifikation der MR-Sequenzen und Monitoring gegeben sowie die Verantwortlichkeiten und Aufklarungsnotwendigkeiten zwischen Radiologie und Kardiologie definiert. Ziel ist es, ein Maximum an Patientensicherheit zu gewahrleisten sowie Rechtssicherheit fur die beteiligten Arzte herzustellen, um insgesamt den Zugang von Patienten mit aktiven kardialen Implantaten zu notwendigen MR-Untersuchungen zu verbessern. Die Kernaussagen dieses Konsensus-Papiers sind wie folgt: 1. Konventionelle SM- und ICD-Systeme sind nicht mehr als eine absolute, sondern als eine relative Kontraindikation fur die Durchfuhrung einer MR-Untersuchung anzusehen. Entscheidend bei Indikationsstellung und Untersuchungsdurchfuhrung sind die Abschatzung des individuellen Nutzen/Risiko-Verhaltnisses, eine umfassende Aufklarung uber „off-label use“ und spezifische Risiken, dezidierte SM-/ICD-bezogene und MR-bezogene Sicherheitsmasnahmen zur weitestgehenden Reduzierung dieser Risiken sowie adaquate Monitortechniken wahrend der MR-Untersuchung. 2. Bedingt MR-sichere („MR conditional“) SM- und ICD-Systeme sind fur eine MR-Untersuchung unter dezidierten Rahmenbedingungen getestet und zugelassen. Entscheidend fur die Patientensicherheit sind hier die genaue Kenntnis und die Einhaltung der fur das jeweilige SM/ICD-System spezifischen Nutzungsbedingungen. 3. Das Risiko eines ICD-Patienten wahrend einer MR-Untersuchung ist aufgrund der hoheren elektrophysiologischen Vulnerabilitat des per se strukturell geschadigten Myokards sowie des hoheren Risikos irreversibler Funktionsstorungen konventioneller ICD-Systeme im Vergleich zu SM-Patienten als deutlich hoher einzuschatzen. Die Indikationsstellung zu einer MR-Untersuchung eines ICD-Patienten sollte somit strenger erfolgen und kritisch hinterfragt werden, ob der zu erwartende Nutzen der MR-Untersuchung in einem adaquaten Verhaltnis zum Risiko steht. 4. Die komplexe Thematik erfordert eine enge und abgestimmte Kooperation zwischen Radiologie und Kardiologie.

// Constantin Lapa 1, * , Theresa Reiter 2, 3, * , Malte Kircher 1 , Andreas Schirbel 1 , Rudolf A. Werner 1 , Theo Pelzer 2 , Carmen Pizarro 4 , Dirk Skowasch 4 , Lena Thomas 5 , Ulrike Schlesinger-Irsch 6 , Daniel Thomas 6 , Ralph A. Bundschuh 5 , Wolfgang R. Bauer 2, 3, * , Florian C. Gartner 5, * 1 Department of Nuclear Medicine, University Hospital Wurzburg, Wurzburg, Germany 2 Department of Internal Medicine, University Hospital Wurzburg, Wurzburg, Germany 3 Comprehensive Heart Failure Center, University Wurzburg, Wurzburg, Germany 4 Department of Internal Medicine II - Pneumology/Cardiology, University Hospital Bonn, Bonn, Germany 5 Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany 6 Department of Radiology, University Hospital Bonn, Bonn, Germany * These authors have contributed equally to this work Correspondence to: Constantin Lapa, email: lapa_c@ukw.de Keywords: sarcoidosis, DOTATOC, SSTR, somatostatin receptor, PET Received: September 01, 2016 Accepted: October 12, 2016 Published: October 21, 2016 ABSTRACT Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with 18 F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV mean ) and maximum standardized uptake values (SUV max ) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR + /PET - subjects, one patient with minor involvement (

A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK−/−) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity ( Vmax) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK−/− mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK−/− mice, but ejection fraction (EF) remained normal. Vmax, however, was significantly reduced in the CK−/− mice [wild-type, 2.32 ± 0.09 vs. CK−/−, 1.43 ± 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 ± 0.11 vs. CK−/− MI, 1.26 ± 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK−/− mice (wild-type, 6.68 ± 0.27 vs. CK−/−, 4.12 ± 0.63 ml/g·min, P < 0.05; and wild-type MI, 3.97 ± 0.65 vs. CK−/− MI, 3.71 ± 0.57 ml/g·min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK−/− phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.

The coronary vascular effect of atrial natriuretic peptide is controversial: Coronary vasodilator as well as constrictor effects have been reported. The controversy may originate from interference of atrial natriuretic peptide with the renin-angiotensin system and/or tachyphylaxis of the effect of atrial natriuretic peptide. The effect of alpha-human atrial natriuretic peptide bolus application on changes of coronary flow was examined in the isolated, constant-pressure perfused rat heart. Six groups were considered: (1) control group; groups in which the renin-angiotensin system was modulated by pretreatment with continuous infusion of: (2) angiotensin II, (3) the angiotensin converting enzyme inhibitor captopril (4) the angiotensin II receptor blocker saralasin; and groups in which tachyphylaxis was examined by pretreatment with ANP, (5) as continuous infusion and (6) as bolus application. First, in control hearts, dose-response curves were obtained for single ANP dosages of 1-100 nmol. The effect of high dosages (40 and 100 nmol) was biphasic, with an initial vasodilator and subsequent long-lasting vasoconstrictor component. Hearts in which coronary flow was reduced by approximately 18% through continuous angiotensin II infusion showed an enhanced early vasodilator response after ANP administration, whereas the vasoconstrictor effect was no longer observable. Angiotensin converting enzyme inhibition and angiotensin II receptor blockade reduced the vasodilator effect of ANP. In addition, saralasin nearly abolished ANP-induced vasoconstriction, whereas vasoconstriction was unaltered by pretreatment with captopril. Captopril or saralasin alone did not change coronary flow, heart rate and left ventricular developed pressure. In groups (5) and (6). ANP bolus application showed significantly reduced vasomotor activity. We conclude that in the isolated rat heart. ANP has a biphasic effect with early vasodilation and late vasoconstriction. Both effects can be modulated by inhibition of the renin-angiotensin system at different levels indicating that vasomotor ANP effects result from interaction of ANP with the local renin-angiotensin system. ANP effects can be markedly reduced by tachyphylaxis.

Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 ± 9%, ischemic region: 9 ± 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 ± 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 ± 0.09) compared with remote (1.27 ± 0.08) and control hearts (1.43 ± 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 ± 1.4%) correlated to ATP signal reduction from remote to the ischemic region ( r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.