Immune interactions and heterogeneity in transmission drives the pathogen-mediated invasion of grey squirrels in the UK.

Mathematical models highlighted the importance of pathogen-mediated invasion, with the replacement of red squirrels by squirrelpox virus (SQPV) carrying grey squirrels in the UK, a well-known example. In this study, we combine new epidemiological models, with a range of infection characteristics, with recent longitudinal field and experimental studies on the SQPV dynamics in red and grey squirrel populations to better infer the mechanistic basis of the disease interaction. A key finding is that a model with either partial immunity or waning immunity and reinfection, where individuals become seropositive on the second exposure to infection, that up to now has been shown in experimental data only, can capture the key aspects of the field study observations. By fitting to SQPV epidemic observations in isolated red squirrel populations, we can infer that SQPV transmission between red squirrels is significantly (4×) higher than the transmission between grey squirrels and as a result our model shows that disease-mediated replacement of red squirrels by greys is considerably more rapid than replacement in the absence of SQPV. Our findings recover the key results of the previous model studies, which highlights the value of simple strategic models that are appropriate when there are limited data, but also emphasise the likely complexity of immune interactions in wildlife disease and how models can help infer disease processes from field data.

Transcatheter valve repair of tricuspid regurgitation with the PASCAL system: TriCLASP study 30-day results.

BACKGROUND: Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. METHODS: TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. RESULTS: Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved ≤moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). CONCLUSION: Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and registered on ClinicalTrials.gov as NCT04614402. The current analysis is an interim report.

High inter- and intra-observer agreement in mapping sequences compared to classical Lake Louise Criteria assessment of myocarditis by inexperienced observers.

AIM: To investigate the observer agreement for the assessment of chronic myocarditis by native T1 and T2 relaxation times, post-contrast T1 relaxation time, and extracellular volume (ECV) fraction, compared to Lake Louise Criteria: oedema ratio (OR) and early gadolinium enhancement ratio (EGEr). MATERIALS AND METHODS: Data were collected retrospectively on 71 consecutive patients who underwent cardiac magnetic resonance imaging as part of a complete diagnostic work-up according to current guidelines for suspected myocarditis. Thirteen cases were excluded due to previous myocardial infarction or technical issues. To test for intra- and interobserver agreement, the determination of the myocardial native T1 and T2 relaxation times, post-contrast T1 relaxation time, ECV, OR and EGEr was undertaken by two medical school graduates after comprehensive training. Bland-Altman analysis and intraclass correlation coefficient (ICC) were assessed. RESULTS: The final analysis included 27 patients with chronic myocarditis, 21 patients with dilated cardiomyopathy and/or hypertensive heart disease, and 10 patients with unremarkable investigations in the control group. Excellent interobserver agreement was obtained for native T1 and T2 relaxation times, post-contrast T1 relaxation time and ECV, with ICC of 0.982/0.977/0.991/0.994, p < 0.001. Interobserver agreement was lower for OR and EGEr, with ICC of 0.841 and 0.818, p < 0.001, respectively. Mapping parameters (cut-off values: T1 1,070 ms, T2 54 ms, ECV 30%) yield good performance in the diagnosis of chronic myocarditis with the best sensitivity/specificity/accuracy of 93%/80%/88% for ECV, followed by 70%/80%/74% for T2, and 52%/88%/69% for T1. CONCLUSIONS: mapping parameters show excellent agreement between observers in the assessment of myocarditis.

Comparison of volumetric and functional parameters in simultaneous cardiac PET/MR: feasibility of volumetric assessment with residual activity from prior PET/CT.

OBJECTIVE: To compare cardiac left ventricular (LV) parameters in simultaneously acquired hybrid fluorine-18-fluorodeoxyglucose ([18F] FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with residual tracer activity of upstream PET/CT. METHODS: Twenty-nine patients (23 men, age 58±17 years) underwent cardiac PET/MRI either directly after a non-cardiac PET/CT with homogenous cardiac [18F] FDG uptake (n=20) or for viability assessment (n=9). Gated cardiac [18F] FDG PET and cine MR sequences were acquired simultaneously and evaluated blinded to the cross-imaging results. Image quality (IQ), end-diastolic (LVEDV), end-systolic volume (LVESV), ejection fraction (LVEF) and myocardial mass (LVMM) were measured. Pearson correlation and intraclass correlation coefficient (ICC), regression and a Bland-Altman analysis were assessed. RESULTS: Except LVMM, volumetric and functional LV parameters demonstrated high correlations (LVESV: r=0.97, LVEDV: r=0.95, LVEF: r=0.91, LVMM: r=0.87, each p<0.05), but wide limits of agreement (LOA) for LVEDV (-25.3-82.5ml); LVESV (-33.1-72.7ml); LVEF (-18.9-14.8%) and LVMM (-78.2-43.2g). Intra- and interobserver reliability were very high (ICC≥0.95) for all parameters, except for MR-LVEF (ICC=0.87). PET-IQ (0-3) was high (mean: 2.2±0.9) with significant influence on LVMM calculations only. CONCLUSION: In simultaneously acquired cardiac PET/MRI data, LVEDV, LVESV and LVEF show good agreement. However, the agreement seems to be limited if cardiac PET/MRI follows PET/CT and only the residual activity is used. KEY POINTS: • [ 18 F] FDG PET-MRI is feasible with residual [ 18 F] FDG activity in patients with homogenous cardiac uptake. • Cardiac volumes and function assessed by PET/MRI show good agreement. • LVEDV and LVESV are underestimated; PET overestimates LVMM and LVEF. • Cardiac PET and MRI data correlate better when acquired simultaneously than sequentially. • PET and MRI should not assess LV parameters interchangeably.

[Myocarditis in the differential diagnosis of cardiomyopathies. Endomyocardial biopsy or MRI?]. / Myokarditis in der Differenzialdiagnose von Kardiomyopathien. Endomyokardiale Biopsie oder MRT?

Myocarditis is an inflammatory disease of the heart muscle commonly caused by viral pathogens. Dilated cardiomyopathy is a major long-term sequela of myocarditis and at least in part related to post-viral immune-mediated responses. Establishing a diagnosis of myocarditis represents a major challenge because of the variable clinical picture and the lack of readily available, non-invasive diagnostic tests. In recent years, cardiac magnetic resonance imaging (cMRI) has emerged as a promising additional diagnostic tool in patients with suspected myocarditis: cMRI not only provides important insights into structural and functional abnormalities of the heart but relevant tissue pathologies can also be visualized. The diagnostic accuracy of three tissue criteria, i.e. the edema ratio, early gadolinium enhancement ratio and late gadolinium enhancement, has been characterized in several studies. Endomyocardial biopsy (EMB) is widely considered to be the reference standard for diagnosis of myocarditis. Although limited by sampling error, EMB is the only diagnostic procedure that can be used to confirm myocarditis. Laboratory analyses of EMB may provide information about specific causes of myocarditis and are, at least in part, of prognostic relevance. In a subset of patients the results of EMB may guide therapeutic decision-making. Additional efforts are needed in cardiac imaging, molecular characterization of EMB and evaluation of serum biomarkers to improve the diagnostic work-up in patients with suspected myocarditis and to identify potential novel targets for a cause-specific therapy of myocarditis.

[Treatment of cardiogenic shock complicating acute myocardial infarction]. / Behandlung des kardiogenen Schocks im Rahmen eines akuten Myokardinfarkts.

While the mortality rate of acute myocardial infarction has decreased drastically in the last decades, the outcome of patients with cardiogenic shock complicating acute myocardial infarction is still devastating. The effectiveness of supportive medicinal therapy of cardiogenic shock is often limited by undesired side effects (e.g. arrhythmia and increased myocardial oxygen consumption) or inadequate hemodynamic support. Mechanical circulatory support in cardiogenic shock failed to show beneficial effects on short-term and long-term survival; however, there are hints for a survival benefit in therapy refractory cardiogenic shock. Therefore, future trials need to evaluate further medicinal treatment options and also the best type of mechanical support as well as the optimal time of initiation to improve the success of therapeutic management.

[Diagnosis and therapy of chronic myocardial ischemia. Role of cardiac magnetic resonance imaging]. / Diagnostik und Therapie der chronischen Myokardischämie. Rolle der kardialen Magnetresonanztomographie.

In patients with chronic coronary artery disease different therapeutic strategies, such as optimal medical therapy, revascularization by percutaneous coronary intervention or coronary artery bypass grafting have been shown to improve the prognosis and symptoms and yield proven superiority over other treatment strategies in different patient populations. Thus, individual assessment of cardiac function and structure is of paramount importance to choose the optimal therapeutic strategy and subsequently improve patient prognosis. In this setting cardiac magnetic resonance imaging (CMR) has been shown to provide important diagnostic information. Myocardial ischemia can be detected by either perfusion stress CMR demonstrating perfusion deficits indicative of hemodynamically relevant coronary artery stenosis or dobutamin stress CMR for objectifying wall motion abnormalities during stress. Both techniques are superior to single photon emission computerized tomography and stress echocardiography in specific patient populations. Myocardial viability can be assessed by means of end-diastolic wall thickness or delayed enhancement imaging which allows quantification of the transmural extent of scarring. Furthermore, low-dose dobutamin stress CMR can detect a contractile reserve. Delayed enhancement imaging leads to accurate results due to its high resolution, can be performed at rest requiring no stress within a short time period and is easy to analyze. Thus this technique can be recommended as the favored technique to assess myocardial viability. In the following article the CMR techniques for ischemia and viability testing will be presented and their role in diagnosis and therapy of chronic myocardial ischemia will be discussed.

Left atrial appendage closure devices. Their role in 2013.

Stroke prevention is the major goal in treating patients with atrial fibrillation. Warfarin therapy, if used appropriately, is highly effective in preventing thromboembolic events, but is simultaneously burdened by a narrow therapeutic window, multiple food and drug interactions, and a substantial bleeding risk. New pharmacological agents show only a modest reduction of bleeding complications compared to warfarin. Percutaneous device left atrial appendage (LAA) closure has now been technologically advanced as an additional and potential alternative to pharmacotherapy in patients with AF. Promising randomized data are obtainable with the WATCHMAN® device, while several other devices are in various stages of clinical and preclinical development. In this article we review the current knowledge and status of this technique.

[MRI for myocarditis]. / MRT bei Myokarditis.

Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation.

[Preoperative and postoperative imaging in patients with transposition of the great arteries]. / Prä- und Postoperative Bildgebung bei Patienten mit Transposition der großen Gefäße.

Transposition of the great arteries (TGA) is a rare disease representing not more than 3-5% of all congenital heart diseases. TGA is a cardiac anomaly in which the aorta arises entirely or largely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle. This is called a ventriculo-arterial discordant connection and when accompanied by an atrio-ventricular concordant connection it is called a complete or D-transposition (D-TGA). The terms congenitally corrected TGA (ccTGA) or L-TGA describe an atrio-ventricular discordant connection. In D-TGA survival can only be achieved if additional shunting is simultaneously present, which possibly has to be created post-natal by the so-called Rashkind maneuver.Nowadays, an early anatomic correction using the arterial switch operation is the treatment of choice. Up to the 1980s, an atrial switch operation according to Senning/Mustard was performed. Apart from echocardiography the imaging modality of choice is usually MRI to assess the complex postoperative anatomy, viability of the myocardium and to perform a volumetric and functional assessment, including MR flow measurements. Multidetector computed tomography (MDCT) is used if there are contraindications to MRI or if an assessment of cardiac and especially coronary anatomy is the main interest.

The consequences of introducing non-indigenous species: two case studies, the grey squirrel in Europe and the brushtail possum in New Zealand.

Two examples of the introduction of non-indigenous invasive species are reviewed: the grey squirrel in Europe (United Kingdom, Ireland and Italy) and the brushtail possum in New Zealand. Both have become very successful in their respective non-native habitats since their introductions in the mid-to-late 19th Century. Both species impact extensively on native biodiversity, environmental sustainability, forestry, and agriculture through a range of direct and indirect mechanisms. Management is currently mainly by lethal control, namely poisoning, trapping and shooting. Such methods of control are, however, increasingly contentious for both species, and alternative, non-lethal methods of population control, e.g. fertility control, are being developed. The case studies highlight many of the issues in invasive animal control; for example, prevention being better than control, lack of good understanding of impacts and the success of control measures on reducing impacts, interactive impacts on native biodiversity and ecosystems, the telling influence of public opinion on management options and, lastly, the need to better inform and educate the public.

Epidemiology of squirrelpox virus in grey squirrels in the UK.

The dramatic decline of the native red squirrel in the UK has been attributed to both direct and disease-mediated competition with the grey squirrel where the competitor acts as a reservoir host of squirrelpox virus (SQPV). SQPV is threatening red squirrel conservation efforts, yet little is known about its epidemiology. We analysed seroprevalence of antibody against SQPV in grey squirrels from northern England and the Scottish Borders in relation to season, weather, sex, and body weight using Generalized Linear Models in conjunction with Structural Equation Modelling. Results indicated a heterogeneous prevalence pattern which is male-biased, increases with weight and varies seasonally. Seroprevalence rose during the autumn and peaked in spring. Weather parameters had an indirect effect on SQPV antibody status. Our findings point towards a direct disease transmission route, which includes environmental contamination. Red squirrel conservation management options should therefore seek to minimize squirrel contact points.

Immediate clinical and haemodynamic benefits of restoration of pulmonary valvar competence in patients with pulmonary hypertension.

OBJECTIVE: To analyse the potential benefit of restoration of pulmonary valvar competence in patients with severe pulmonary regurgitation (PR) and pulmonary hypertension (PH) associated with congenital heart disease. DESIGN: Retrospective study. SETTING: Tertiary paediatric and adult congenital heart cardiac centre. INTERVENTIONS: Percutaneous pulmonary valve implantation (PPVI). PATIENTS: All patients who underwent PPVI for treatment of PR in the presence of PH (mean PAP >25 mm Hg). RESULTS: Seven patients with severe PH as a result of congenital heart disease and severe PR underwent PPVI. The valve implantation procedure was feasible and uncomplicated in all seven cases, successfully abolishing PR. There was a significant increase in diastolic (15.4 (7.3) to 34.0 (8.5) mm Hg; p = 0.007) and mean (29.7 (8.1) to 41.3 (12.9) mm Hg; p = 0.034) pulmonary artery pressures, and an improvement in NYHA functional class (from median IV to median III; p<0.008). Peripheral oxygen saturations rose from 85.9% (11.0%) to 91.7% (8.3%) (p = 0.036). Right ventricular (RV) volumes decreased (from 157.0 (44.7) to 140.3 (53.3) ml/m(2)), while effective RV stroke volume increased (from 23.4 (9.3) to 41.0 (11.6) ml/m(2)). During a median follow-up of 20.3 months (range 1.3-47.5), valvar competence was well maintained despite near systemic pulmonary pressures. None of the valved stents were explanted during follow-up. CONCLUSION: Trans-catheter treatment of PR in patients with PH is well tolerated and leads to clinical and haemodynamic improvement, most probably caused by a combination of increased pulmonary perfusion pressures and RV efficiency.

Percutaneous implantation of a pulmonary valve: an illustrative case.

Surgical reconstruction of the right ventricular outflow tract (RVOT) with valved conduits in infants and children with congenital heart disease leads to re-intervention in later life as the ensuing pulmonary regurgitation and stenosis of the degenerating conduit impacts negatively on right ventricular function. Percutaneous pulmonary valve implantation (PPVI) provides a safe alternative to early surgical re-intervention in these patients. We describe this procedure as performed on an 11- year-old boy. Difficulty may be experienced crossing the RVOT prior to PPVI. We describe several techniques that may be used to encourage the distal movement of the delivery system through the RVOT. (Neth Heart J 2007;15:27-30.).

Disease threats posed by alien species: the role of a poxvirus in the decline of the native red squirrel in Britain.

Red squirrels are declining in the United Kingdom. Competition from, and squirrel poxvirus (SQPV) disease carried by, grey squirrels are assumed to be determining the decline. We analyse the incidence of disease and changes in distribution of the two species in Cumbria, from 1993 to 2003 and compare these to the predictions of an individual-based (IB) spatially explicit disease model simulating the dynamics of both squirrel species and SQPV in the landscape. Grey squirrels increased whilst red squirrels declined over 10 years. The incidence of disease in red squirrels was related to the time since grey squirrels arrived in the landscape. Analysis of rates of decline in red squirrel populations in other areas showed that declines are 17-25 times higher in regions where SQPV is present in grey squirrel populations than in those where it is not. The IB model predicted spatial overlap of 3-4 years between the species that was also observed in the field. The model predictions matched the observed data best when contact rates and rates of infection between the two species were low. The model predicted that a grey squirrel population control of >60% effective kill was needed to stop the decline in red squirrel populations in Cumbria.

Impact of landscape management on the genetic structure of red squirrel populations.

Landscape management practices that alter the degree of habitat fragmentation can significantly affect the genetic structure of animal populations. British red squirrels use "stepping stone" patches of habitat to move considerable distances through a fragmented habitat. Over the past few decades, the planting of a large conifer forest has connected groups of forest fragments in the north of England with those in southern Scotland. This "defragmentation" of the landscape has resulted in substantial genetic mixing of Scottish and Cumbrian genes in squirrel populations up to 100 kilometers from the site of the new forest. These results have implications for the conservation management of animal and plant species in fragmented landscapes such as those found in Britain.