Quantitative analysis of pre- and post-operative valvular annulus deformations following valvular insufficiency

Valvular insufficiency is a growingly common valvular heart disease that frequently is associated with regurgitation. Atrioventricular incompetency can lead to overall ventricular and atrial enlargement, volume overload, heart impairment and, if not treated, can culminate in heart failure. With the advances in technology and the increasing interest in devices that have lower post-operative burden on patients, transcatheter mitral and tricuspid valve repair systems are going through a phase of rapid development and growing use. In this work, we aimed to quantitatively assess the morphology of mitral and tricuspid annuli in patients who underwent transcatheter valve repair with MitraClip/TriClip, before and after the intervention, using three-dimensional transoesophageal echocardiography images, in order to evaluate the geometrical changes of the annulus following the intervention. For our purposes, firstly, we implemented a tool for the visualization and navigation of the volumetric data across the cardiac cycle. Then, in order to track the annulus over the cardiac cycle, we extracted five rotational slices from the volume data, selected two initial points on each slice, and tracked these points across the cardiac cycle using KLT algorithm. In a first stage we led a parameters optimization for the tracking method, and we studied the sensitivity of the KLT algorithm to the initialization points, that are manually chosen by the user. In a second stage, we analysed 10 subjects (5 for mitral regurgitation and 5 for tricuspid regurgitation), tracking their annulus before and after valve repairment. In conclusion, we found in all our 10 subjects that immediately after the intervention there is a shortening of the major diameters of the valves, mainly the shortest diameter, due to the clip application, that leads to a reduction of the perimeter and the area of the annulus.

Parametric Sensitivity Analysis of the Most Recent Computational Models of Rabbit Cardiac Pacemaking

The cellular basis of cardiac pacemaking activity, and specifically the quantitative contributions of particular mechanisms, is still debated. Reliable computational models of sinoatrial nodal (SAN) cells may provide mechanistic insights, but competing models are built from different data sets and with different underlying assumptions. To understand quantitative differences between alternative models, we performed thorough parameter sensitivity analyses of the SAN models of Maltsev & Lakatta (2009) and Severi et al (2012). Model parameters were randomized to generate a population of cell models with different properties, simulations performed with each set of random parameters generated 14 quantitative outputs that characterized cellular activity, and regression methods were used to analyze the population behavior. Clear differences between the two models were observed at every step of the analysis. Specifically: (1) SR Ca2+ pump activity had a greater effect on SAN cell cycle length (CL) in the Maltsev model; (2) conversely, parameters describing the funny current (If) had a greater effect on CL in the Severi model; (3) changes in rapid delayed rectifier conductance (GKr) had opposite effects on action potential amplitude in the two models; (4) within the population, a greater percentage of model cells failed to exhibit action potentials in the Maltsev model (27%) compared with the Severi model (7%), implying greater robustness in the latter; (5) confirming this initial impression, bifurcation analyses indicated that smaller relative changes in GKr or Na+-K+ pump activity led to failed action potentials in the Maltsev model. Overall, the results suggest experimental tests that can distinguish between models and alternative hypotheses, and the analysis offers strategies for developing anti-arrhythmic pharmaceuticals by predicting their effect on the pacemaking activity.