Flow patterns in ascending aortic aneurysms: Determining the role of hypertension using phase contrast magnetic resonance and computational fluid dynamics.

Thoracic aortic aneurysm (TAA) is a local dilation of the thoracic aorta. Although universally used, aneurysm diameter alone is a poor predictor of major complications such as rupture. There is a need for better biomarkers for risk assessment that also reflect the aberrant flow patterns found in TAAs. Furthermore, hypertension is often present in TAA patients and may play a role in progression of aneurysm. The exact relation between TAAs and hypertension is poorly understood. This study aims to create a numerical model of hypertension in the aorta by using computational fluid dynamics. First, a normotensive state was simulated in which flow and resistance were kept unaltered. Second, a hypertensive state was modeled in which blood inflow was increased by 30%. Third, a hypertensive state was modeled in which the proximal and peripheral resistances and capacitance parameters from the three-element Windkessel boundary condition were adjusted to mimic an increase in resistance of the rest of the cardiovascular system. One patient with degenerative TAA and one healthy control were successfully simulated at hypertensive states and were extensively analyzed. Furthermore, three additional TAA patients and controls were simulated to validate our method. Hemodynamic variables such as wall shear stress, oscillatory shear index, endothelial cell activation potential (ECAP), vorticity and helicity were studied to gain more insight on the effects of hypertension on flow patterns in TAAs. By comparing a TAA patient and a control at normotensive state at peak-systole, helicity and vorticity were found to be lower in the TAA patient throughout the entire domain. No major changes in flow and flow derived quantities were observed for the TAA patient and control when resistance was increased. When flow rate was increased, regions with high ECAP values were found to reduce in TAA patients in the aneurysm region which could reduce the risk of thrombogenesis. Thus, it may be important to assess cardiac output in patients with TAA.

Mitral prolapsing volume is associated with increased cardiac dimensions in patients with mitral annular disjunction.

INTRODUCTION: In patients with mitral annular disjunction (MAD), it can be difficult to assess the severity of mitral regurgitation (MR), as they present with a prolapsing volume (i.e. volume resulting from mitral valve prolapse, blood volume shift) rather than a regurgitant jet. The influence of the mitral prolapsing volume (MPV) on cardiac dimensions is unknown. We hypothesised that the severity of MR is underestimated in these patients. Our aim was to measure MPV and to investigate its influence on cardiac dimensions in patients with MAD. METHODS: We retrospectively included 131 consecutive patients with MAD from our institution's echocardiographic database. Transthoracic echocardiography was used to assess MPV. Additionally, we established a control group of 617 consecutive patients with degenerative mitral valve disease and performed propensity score matching. RESULTS: Median MPV in the MAD group was 12 ml. MPV was an independent predictor for left ventricular end-diastolic (LVEDD) and end-systolic diameter (LVESD) and left atrial volume (all p < 0.001). In patients with large prolapsing volumes (> 15 ml), LVEDD (56 ± 6 mm vs 51 ± 6 mm, p < 0.001), LVESD [38 mm (34-41) vs 34 mm (31-39), p < 0.01] and left atrial volume [105 ml (86-159) vs 101 ml (66-123), p = 0.04] were significantly increased compared to matched patients with degenerative mitral valve disease and similarly assessed severity of MR. CONCLUSION: Due to a volume shift based on the MPV rather than an actual regurgitant jet, MR severity cannot be assessed adequately in MAD patients. Increased MPV induces ventricular and atrial enlargement. These findings warrant future studies to focus on MPV as an additional parameter for assessment of the severity of MR in MAD patients.

Determining the optimal interval for imaging surveillance of ascending aortic aneurysms.

BACKGROUND: Cardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs. METHODS: A total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred. RESULTS: The mean growth rate in our population was 0.2 ± 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 ± 0.5 vs 0.2 ± 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40-49 mm in diameter and yearly imaging of those measuring 50-54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%. CONCLUSIONS: In our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach.

Organisation of care for patients using direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are recommended by several scientific societies as first-line therapy for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, there is uncertainty regarding the organisation of anticoagulation care, with various caregivers being involved. Patients and caregivers are often confronted by uncertainty about the coordination of treatment. With the functional resonance analysis method we visualised the process of anticoagulation care in daily practice in the Maastricht region. This resulted in recommendations on how to improve the organisation of anticoagulation care for DOAC patients.

Cardiac shockwave therapy in patients with chronic refractory angina pectoris.

BACKGROUND: Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. METHODS: We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3-7 spots/session, 100 impulses/spot, 0.09 mJ/mm(2)) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. RESULTS: One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p < 0.01) and the angina symptoms diminished from CCS class III to CCS class II (p < 0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2 ± 7.7 % to 56.4 ± 9.4 %, p = 0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015). No clinically relevant side effects were observed. CONCLUSION: CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: To investigate the prevalence and prognostic relevance of cardiac involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis (GPA) patients. METHODS: Prospective cohort study of fifty EGPA and forty-one GPA patients in sustained remission without previous in-depth cardiac screening attending our clinical immunology outpatient department. Cardiac screening included clinical evaluation, ECG, 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR) with coronary angiography and endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk factor-matched control subjects were randomly selected from a population study. Long-term outcome was assessed using all-cause and cardiovascular mortality. RESULTS: A total of 91 AAV-patients (age 60±11, range 63-87years) were compared to 50-matched control subjects (age 60±9years, range 46-78years). ECG and echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA patients vs 20% controls (P<0.001 and P=0.014, respectively). A total of 69 AAV-patients underwent additional CMR, slightly increasing the prevalence of cardiac involvement to 66% in EGPA and 61% in GPA patients. After a mean follow-up of 53±18months, presence of cardiac involvement using ECG and echocardiography in AAV-patients showed increased all-cause and cardiovascular mortality (Log-rank P=0.015 and Log-rank P=0.021, respectively). CONCLUSION: Cardiac involvement in EGPA and GPA patients with sustained remission is high, even if symptoms are absent and ECG is normal. Moreover, cardiac involvement is a strong predictor of (cardiovascular) mortality. Therefore, risk stratification using cardiac imaging is recommended in all AAV-patients, irrespective of symptoms or ECG abnormalities.

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging.

BACKGROUND: Dilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure. METHODS AND RESULTS: A well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography. After multivariable linear regression, four factors independently influenced RVEF (R(2) = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = - 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = - 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37-55 %) versus 56 % (IQR 48-63 %), p < 0.05. CONCLUSIONS: In patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.

Severe mitral regurgitation caused by eosinophilic endocarditis.

We describe a patient with symptoms of heart failure caused by severe mitral regurgitation. Echocardiography revealed an intracardiac mass embedding the posterior mitral valve leaflet, and cardiac magnetic resonance imaging showed two intracardiac thrombi and endomyocardial fibrosis. Eosinophil count kept rising and a mutation in the gene for platelet-derived growth factor receptor alpha was found. The combination of these findings led to the diagnosis of Loeffler's endocarditis. Treatment with prednisone and a tyrosine kinase inhibitor resulted in complete remission of the hypereosinophilia and mitral valve regurgitation was only mild at 9-month follow-up visit. .

Exercise related ventricular arrhythmias are related to cardiac fibrosis in hypertrophic cardiomyopathy mutation carriers.

AIMS: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) due to exercise-related ventricular arrhythmias (ERVA); however the pathological substrate is uncertain. The aim was to determine the prevalence of ERVA and their relation with fibrosis as determined by cardiac magnetic resonance imaging (CMR) in carriers of an HCM causing mutation. METHODS: We studied the prevalence and origin of ERVA and related these with fibrosis on CMR in a population of 31 HCM mutation carriers. RESULTS: ERVA occurred in seven patients (23%) who all showed evidence of fibrosis (100% ERVA(+) vs. 58% ERVA(-), p = 0.04). No ventricular tachycardia or ventricular fibrillation occurred. In patients with ERVA, the extent of fibrosis was significantly larger (8 ± 4% vs. 3 ± 4%, p = 0.02). ERVA originated from areas with a high extent of fibrosis or regions directly adjacent to these areas. CONCLUSIONS: ERVA in HCM mutation carriers arose from the area of fibrosis detected by CMR; ERVA seems closely related to cardiac fibrosis. Fibrosis as detected by CMR should be evaluated as an additional risk factor to further delineate risk of SCD in carriers of an HCM causing mutation.

Giant cell myocarditis triggered by a parvovirus B19 infection.

Giant cell myocarditis (GCM) is an uncommon inflammatory heart disease with a rapid progression and a devastating outcome. Its exact cause is unknown, but it has been associated with various inflammatory and autoimmune disorders. The authors report a case where GCM is triggered by a parvovirus B19 (PVB19) infection.

Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We describe a family in which members carry either a single mutation or are double heterozygous for mutations in myosin heavy chain gene (MYH7) and cysteine and glycine-rich protein 3 (CSRP3). The described family emphasises the idea of a more severe clinical phenotype with double-heterozygous mutations. It also highlights the importance of cardiological screening where NT-proBNP may serve as an added diagnostic tool.Conclusion. With a more severe inexplicable phenotype of HCM within a family, one should consider the possibility of double-heterozygous mutations. This implies that in such families, even when one disease-causing mutation is found, all the family members still have an implication for cardiological screening parallel to extended genetic screening. (Neth Heart J 2009;17:458-63.).

Magnetic resonance imaging of the coronary arteries.

Despite progress in prevention and early diagnosis, coronary artery disease (CAD) remains one of the leading causes of mortality in the world. For many years, invasive X-ray coronary angiography has been the method of choice for the diagnosis of significant CAD. However, up to 40% of patients referred for elective X-ray coronary angiography have no clinically significant stenoses. These patients still remain subjected to the potential risks of X-ray angiography. As an alternative, magnetic resonance imaging (MRI) is currently one of the most promising techniques for noninvasive imaging of the coronary arteries. Over the past two decades, many technical developments have been implemented that have led to major improvements in coronary MRI. Nowadays, both anatomical and functional information can be obtained with high temporal and spatial resolution and good image quality. In this review we will discuss the technical foundations and current status of clinical coronary MRI, and some potential future applications.

Influence of different dose rates on cell recovery and RBE at different spatial positions during protracted conformal radiotherapy.

The effect of simultaneous induction and repair of sub-lethal lesions during protracted irradiation is potentially important for conformal irradiation techniques and may influence the relative biological effectiveness (RBE) of different radiation qualities. The importance of repair for 50 kV X rays from a miniaturised X-ray source producing an essentially isotropic dose distribution for intra-operative radiotherapy (IORT) was verified for inactivation of V79 cells in different distances from the source. The experimental data were evaluated in terms of the linear-quadratic model and the generalised Lea-Catcheside time factor. Furthermore, the shape of survival curves for 14 MeV [d(0.25) + T] neutrons at different dose rates implicated a role of repair for fast neutrons. Microdosimetric measurements have previously demonstrated variations in radiation quality between different positions in a therapy phantom for conformal moving-beam therapy with this radiation. Experimental data on the effectiveness for inactivation of V79 cells irradiated at such positions are presented and the influence of repair is analysed.

Multi-slice dynamic imaging: complete functional cardiac MR examination within 15 seconds.

A new magnetic resonance (MR) sequence was developed to acquire real-time images in a multi-slice dynamic imaging mode to cover the complete heart in 15 seconds without the need for electrocardiogram (ECG) triggering and multiple breath holds. In 34 patients, left ventricular function was assessed with the new technique and a standard technique. The new technique proved to be feasible and accurate for functional cardiac examinations.

Magnetic resonance flow measurements in real time: comparison with a standard gradient-echo technique.

Ultrafast gradient systems and hybrid imaging sequences offer the opportunity to acquire phase contrast flow data in real time. In a 1.5-Tesla magnetic resonance (MR)-tomograph, peak velocity and volume flow were assessed in 36 large vessels (aorta) and 33 medium-sized vessels (carotid and iliac artery) using a real-time (segmented k-space turbo gradient-echo planar imaging sequence) in comparison with a gradient-echo technique. With the real-time technique, the matrix was reduced from 116 to 64, and temporal resolution changed from 30 msec to 124 msec. Measurements of peak velocity correlated in large (r = 0.88) and medium-sized vessels (r = 0.81). Volume flow measurements correlated in large vessels (r = 0.87), however, a poor correlation (r = 0.64) was found in medium-sized vessels. Thus, scan time can be significantly reduced and images acquired without electrocardiogram (ECG)-triggering. Flow volume can only be determined in large vessels with sufficient accuracy, mainly due to reduced spatial resolution in smaller vessels.

Comparison of magnetic resonance real-time imaging of left ventricular function with conventional magnetic resonance imaging and echocardiography.

This study analyzes the accuracy of a new real-time magnetic resonance imaging (MRI) technique (acquisition duration, 62 ms/image) and echocardiography for the determination of left ventricular (LV) end-diastolic volume, end-systolic volume, ejection fraction, and muscle mass when compared with turbo gradient echo imaging as the reference standard. Thirty-four patients were examined with digital echocardiography, standard, and real-time MRI. A close correlation was found between the results of real-time imaging and the reference standard for end-diastolic volume, end-systolic volume, and ejection fraction (r >0.95), with a lower correlation for LV muscle mass (r = 0.81). Correlations between echocardiography and the reference standard were lower for all parameters. Real-time MRI enables the acquisition of high-quality cine loops of the entire heart in minimal time without electrocardiographic triggering or breath holding. Thus, patient setup and scan time can be reduced considerably. Results are similar to the reference standard and superior to echocardiography for determining LV volumes and ejection fraction. This technique is a valid alternative to current approaches and can form the basis of every cardiac MRI examination.

Magnetic resonance real-time imaging for the evaluation of left ventricular function.

New ultrafast gradient systems and hybrid imaging sequences make it possible to acquire a complete image in real time, without the need for breathholding or electrocardiogram (ECG) triggering. In 21 patients, left ventricular function was assessed by the use of a turbo-gradient echo technique, an echo-planar imaging (EPI) technique, and a new real-time imaging technique. End-diastolic and end-systolic volumes, left ventricular muscle mass, and ejection fraction of the ultrafast techniques were compared with the turbo-gradient echo technique. Inter- and intraobserver variability was determined for each technique. Image quality was sufficient for automated contour detection in all but two patients in whom foldover occurred in the real-time images. Results of the ultrafast imaging techniques were comparable with conventional turbo-gradient echo techniques. There was a tendency to overestimate the end-diastolic volume by 3.9 and 1.3 ml with EPI real-time imaging, the end-systolic volume by 0.9 and 5.0 ml, and the left ventricular mass by 2.6 and 23.8 g. Ejection fraction showed a tendency to be overestimated by 1.1% with EPI and underestimated by 4.5% with real-time imaging. Correlation between EPI real-time imaging and turbo-gradient echo were 0.94 and O.95, respectively, for end-diastolic volumes, 0.98 and 0.96, respectively, for end-systolic volumes, and 0.96 and 0.89, respectively, for left ventricular mass. Inter- and intraobserver variability was low with all three techniques. Real-time imaging allows an accurate determination of left ventricular function without ECG triggering. Scan times can be reduced significantly with this new technique. Further studies will have to assess the value of real-time imaging for the detection of wall motion abnornmalities and the imaging of patients with atrial fibrillation.

Morphological and compositional changes in a planktonic bacterial community in response to enhanced protozoan grazing.

We analyzed changes in bacterioplankton morphology and composition during enhanced protozoan grazing by image analysis and fluorescent in situ hybridization with group-specific rRNA-targeted oligonucleotide probes. Enclosure experiments were conducted in a small, fishless freshwater pond which was dominated by the cladoceran Daphnia magna. The removal of metazooplankton enhanced protozoan grazing pressure and triggered a microbial succession from fast-growing small bacteria to larger grazing-resistant morphotypes. These were mainly different types of filamentous bacteria which correlated in biomass with the population development of heterotrophic nanoflagellates (HNF). Small bacterial rods and cocci, which showed increased proportion after removal of Daphnia and doubling times of 6 to 11 h, belonged nearly exclusively to the beta subdivision of the class Proteobacteria and the Cytophaga-Flavobacterium cluster. The majority of this newly produced bacterial biomass was rapidly consumed by HNF. In contrast, the proportion of bacteria belonging to the gamma and alpha subdivisions of the Proteobacteria increased throughout the experiment. The alpha subdivision consisted mainly of rods that were 3 to 6 microm in length, which probably exceeded the size range of bacteria edible by protozoa. Initially, these organisms accounted for less than 1% of total bacteria, but after 72 h they became the predominant group of the bacterial assemblage. Other types of grazing-resistant, filamentous bacteria were also found within the beta subdivision of Proteobacteria and the Cytophaga-Flavobacterium cluster. We conclude that the predation regimen is a major structuring force for the bacterial community composition in this system. Protozoan grazing resulted in shifts of the morphological as well as the taxonomic composition of the bacterial assemblage. Grazing-resistant filamentous bacteria can develop within different phylogenetic groups of bacteria, and formerly underepresented taxa might become a dominant group when protozoan predation is the major selective pressure.