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Domestic pigs are widely used in cardiovascular research as the porcine circulatory system bears a remarkable resemblance to that of humans. In order to reduce variability, only clinically healthy animals enter the study as their health status is assessed in entry examination. Like humans, pigs can also suffer from congenital heart disease, such as an atrial septal defect (ASD), which often remains undetected. Due to the malformation of the endocardial cushion during organ development, mitral valve defects (e.g., mitral clefts) are sometimes associated with ASDs, further contributing to hemodynamic instability. In this work, we report an incidental finding of a hemodynamically highly relevant ASD in the presence of incompetent mitral and tricuspid valves, in an asymptomatic, otherwise healthy juvenile pig. In-depth characterization of the cardiac blood flow by four-dimensional (4D) flow magnetic resonance imaging (MRI) revealed a prominent diastolic left-to-right and discrete systolic right-to-left shunt, resulting in a pulmonary-to-systemic flow ratio of 1.8. Severe mitral (15 mL/stroke) and tricuspid (22 mL/stroke) regurgitation further reduced cardiac output. Pathological examination confirmed the presence of an ostium primum ASD and found a serous cyst of lymphatic origin that was filled with clear fluid partially occluding the ASD. A large mitral cleft was identified as the most likely cause of severe regurgitation, and histology showed mild to moderate endocardiosis in the coaptation area of both atrio-ventricular valves. In summary, although not common, congenital heart defects could play a role as a cause of experimental variability or even intra-experimental mortality when working with apparently heathy, juvenile pigs., Frontiers in Veterinary Science, 8, ISSN:2297-1769

Aims Myocardial involvement is common in patients with systemic sclerosis (SSc) and causes myocardial fibrosis and subtle ventricular dysfunction. However, the temporal onset of myocardial involvement during the progression of the disease and its prognostic value are yet unknown. We used cardiovascular magnetic resonance (CMR) to investigate subclinical functional impairment and diffuse myocardial fibrosis in patients with very early diagnosis of SSc (VEDOSS) and established SSc and examined whether this was associated with mortality. Methods and results One hundred and ten SSc patients (86 established SSc, 24 VEDOSS) and 15 healthy controls were prospectively recruited. The patients were followed-up for a median duration of 7.0 years (interquartile range 6.0–7.3 years). Study subjects underwent CMR including assessment of myocardial fibrosis [native T1 and extracellular volume (ECV)] and measurement of global longitudinal (GLS) and circumferential (GCS) myocardial strain. Native T1 values and ECV were elevated in VEDOSS and SSc patients compared with controls (P < 0.001). GLS was similar in VEDOSS and controls but significantly impaired in patients with established SSc (P < 0.001). GCS was similar over all groups (P = 0.88). There were 12 deaths during follow-up. Elevated native T1 [hazard ratio (HR) 5.8, 95% confidence interval (CI): 1.7–20.4; P = 0.006] and reduced GLS (HR 6.1, 95% CI: 1.3–29.9; P = 0.038) identified subjects with increased risk of death. Only native T1 was predictive for cardiovascular mortality (P < 0.001). Conclusion Subclinical myocardial involvement first manifests as diffuse myocardial fibrosis identified by the expansion of ECV and increased native T1 in VEDOSS patients while subtle functional impairment only occurs in established SSc. Native T1 and GLS have prognostic value for all-cause mortality in SSc patients.

Cardiac diffusion tensor imaging (cDTI) provides invaluable information about the state of myocardial microstructure. For further clinical dissemination, free-breathing acquisitions are desired, which however require image registration prior to tensor estimation. Due to the varying contrast and the intrinsically low signal-to-noise ratio (SNR), registration is very challenging and thus can introduce additional errors in the tensor estimation. In the work at hand it is hypothesized, that by incorporating spatial information and physiologically plausible priors into the fitting algorithm, the robustness of diffusion tensor estimation can be improved. To this end, we present a parameterized pipeline to generate synthetic data, that captures the statistics including spatial correlations of diffusion tensors and motion of the heart. The synthetic data is used to train a residual convolutional neural network (CNN) to estimate diffusion tensors from unregistered in-vivo cDTI data. Using in-silico data, the synthetically trained CNN is demonstrated to yield increased tensor estimation accuracy and precision when compared to conventional registration followed by least squares fitting. The network outputs fewer outliers especially at the myocardial borders. In-vivo feasibility using data from five healthy subjects demonstrates the utility of the synthetically trained network. The in-vivo results predicted by the synthetically trained CNN are found to be consistent with the registered least-squares estimates while showing fewer outliers and reduced noise. Even in low SNR regimes, the network results in robust tensor estimation, enabling scan time reduction by reduced-average acquisition in-vivo. Finally, to investigate the network's capability of discriminating between healthy and lesioned tissue, the in-vivo data was artificially augmented showing preserved classification of tissue states based on diffusion metrics., Computerized medical imaging and graphics, 99, ISSN:0895-6111

Objectives: Paravalvular leakage (PVL) and eccentric aortic regurgitation remain a major clinical concern in patients receiving transcatheter aortic valve replacement (TAVR), and regurgitant volume remains the main readout parameter in clinical assessment. In this work we investigate the effect of jet origin and trajectory of mild aortic regurgitation on left ventricular hemodynamics in a porcine model. Methods: A pig model of mild aortic regurgitation/PVL was established by transcatheter piercing and dilating the non-coronary (NCC) or right coronary cusp (RCC) of the aortic valve close to the valve annulus. The interaction between regurgitant blood and LV hemodynamics was assessed by 4D flow cardiovascular MRI. Results: Six RCC, six NCC, and two control animals were included in the study and with one dropout in the NCC group, the success rate of model creation was 93%. Regurgitant jets originating from NCC were directed along the ventricular side of the anterior mitral leaflet and integrated well into the diastolic vortex forming in the left ventricular outflow tract. However, jets from the RCC were orientated along the septum colliding with flow within the vortex, and progressing down to the apex. As a consequence, the presence as well as the area of the vortex was reduced at the site of impact compared to the NCC group. Impairment of vortex formation was localized to the area of impact and not the entire vortex ring. Blood from the NCC jet was largely ejected during the following systole, whereas ejection of large portion of RCC blood was protracted. Conclusions: Even for mild regurgitation, origin and trajectory of the regurgitant jet does cause a different effect on LV hemodynamics. Septaly oriented jets originating from RCC collide with the diastolic vortex, reduce its size, and reach the apical region of the left ventricle where blood resides extendedly. Hence, RCC jets display hemodynamic features which may have a potential negative impact on the long-term burden to the heart., Frontiers in Cardiovascular Medicine, 8, ISSN:2297-055X

Additional file 1: Table S1. Native T1, T2, extra cellular volume (ECV), mean diffusivity (MD) and fractional anisotropy (FA) for healthy controls and for the remote as well as infarcted zone of the infarct cohort. The asterisk indicates statistically significant differences between infarcted and remote regions (p