Supersonic shear-wave elastography and APRI for the detection and staging of liver disease in pediatric cystic fibrosis

Background: Current diagnostic methods for the diagnosis of Cystic fibrosis (CF)-associated liver disease (CFLD) are non-specific and assessment of disease progression is difficult prior to the advent of advanced disease with portal hypertension. This study investigated the potential of Supersonic shear-wave elastography (SSWE) to non-invasively detect CFLD and assess hepatic fibrosis severity in children with CF. Methods: 125 children were enrolled in this study including CFLD (n = 55), CF patients with no evidence of liver disease (CFnoLD = 41) and controls (n = 29). CFLD was diagnosed using clinical, biochemical and imaging best-practice guidelines. Advanced CFLD was established by the presence of portal hypertension and/or macronodular cirrhosis on ultrasound. Liver stiffness measurements (LSM) were acquired using SSWE and diagnostic performance for CFLD detection was evaluated alone or combined with aspartate aminotransferase-to-platelet ratio index (APRI). Results: LSM was significantly higher in CFLD (8.1 kPa, IQR = 6.7–11.9) versus CFnoLD (6.2 kPa, IQR = 5.6–7.0; P < 0.0001) and Controls (5.3 kPa, IQR = 4.9–5.8; P < 0.0001). LSM was also increased in CFnoLD versus Controls (P = 0.0192). Receiver Operating Characteristic (ROC) curve analysis demonstrated good diagnostic accuracy for LSM in detecting CFLD using a cut-off = 6.85 kPa with an AUC = 0.79 (Sensitivity = 75%, Specificity = 71%, P < 0.0001). APRI also discriminated CFLD (AUC = 0.74, P = 0.004). Classification and regression tree modelling combining LSM + APRI showed 14.8 times greater odds of accurately predicting CFLD (AUC = 0.84). The diagnostic accuracy of SSWE for discriminating advanced disease was excellent with a cut-off = 9.05 kPa (AUC = 0.95; P < 0.0001). Conclusions: SSWE-determined LSM shows good diagnostic accuracy in detecting CFLD in children, which was improved when combined with APRI. SSWE alone discriminates advanced CFLD

Ablation as targeted perturbation to rewire communication network of persistent atrial fibrillation

<div><p>Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and global connectivity, but also patient-specific metrics that could serve as a valid endpoint for therapeutic interventions.</p></div

Patient enrollment.

<p>EGM, electrogram.</p

Ablation sites guided by the focal impulse and rotor modulation mapping system.

<p>Blue circles indicate ablation sites. SVC, superior vena cava; IVC, inferior vena cava; RAA, right atrial appendage; LAA, left atrial appendage; RSPV, right superior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; LIPV, left inferior pulmonary vein.</p

Mutual information estimation by <i>k</i>-nearest neighbor statistics in the joint space.

<p><b><i>A</i>.</b><i>Preprocessed time series within the observation window (10 seconds) at electrode X and Y;</i><b><i>B</i>.</b><i>Two-dimensional (2-D) joint space Z =</i> (<i>X</i>, <i>Y</i>)<i>;</i> <b><i>C</i></b>. <i>Determination of ε</i>_<i>x</i>(<i>i</i>), <i>ε</i>_<i>y</i>(<i>i</i>), <i>n</i>_<i>x</i>(<i>i</i>) and <i>n</i>_<i>y</i>(<i>i</i>) <i>for a sample z</i>_<i>i</i> <i>(x</i>_<i>i</i>, <i>y</i>_<i>i</i><i>)</i>. A case for <i>k = 4</i> is shown.</p

Patient demographics.

<p>Data are presented as mean ± standard deviation or n (%). P-value was calculated between patients with recurrence and no recurrence using Pearson's <i>χ</i>² test for categorical variables and Student’s <i>t</i>-tests for continuous variables. AF, atrial fibrillation; CHA₂DS₂-VASc, combined stroke risk score: Cardiac failure, Hypertension, Age ≥65 or 75 years, Diabetes, prior Stroke/ transient ischemic attack (TIA), VAscular disease, Sex category; LA, left atrial; LV, left ventricular.</p