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Introduction The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes. Methods and Results We analyzed Cardiac Magnetic Resonance (CMR) studies of 74 mutation-positive ARVD/C patients for regional abnormalities on a 5-segment RV and 17-segment LV model. The location of electroanatomic endo- and epicardial scar and site of successful VT ablation was recorded in 11 ARVD/C subjects. Among 54/74 (73%) subjects with abnormal CMR, the RV was abnormal in almost all (96%), and 52% had biventricular involvement. Isolated LV abnormalities were uncommon (4%). Dyskinetic basal inferior wall (94%) was the most prevalent RV abnormality, followed by basal anterior wall (87%) dyskinesis. Subepicardial fat infiltration in the posterolateral LV (80%) was the most frequent LV abnormality. Similar to CMR data, voltage maps revealed scar (<0.5 mV) in the RV basal inferior wall (100%), followed by the RV basal anterior wall (64%) and LV posterolateral wall (45%). All 16 RV VTs originated from the basal inferior wall (50%) or basal anterior wall (50%). Of 3 LV VTs, 2 localized to the posterolateral wall. In both modalities, RV apical involvement never occurred in isolation. Conclusion Mutation-positive ARVD/C exhibits a previously unrecognized characteristic pattern of disease involving the basal inferior and anterior RV, and the posterolateral LV. The RV apex is only involved in advanced ARVD/C, typically as a part of global RV involvement. These results displace the RV apex from the Triangle of Dysplasia, and provide insights into the pathophysiology of ARVD/C.

These deep venous injuries appear to preserve the subplate zone, which is likely to be a significant element to consider in the perspective of the neurodevelopmental outcome.

Background Incomplete penetrance and variable expressivity of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) complicate family screening. Objectives To determine the optimal approach to longitudinal follow-up regarding (1) screening interval and (2) testing strategy in at-risk relatives of ARVD/C patients. Methods We included 117 relatives (45% male, 33.3±16.3 years) from 64 families who were at risk of developing ARVD/C by virtue of their familial predisposition (72% mutation carriers [92% Plakophilin-2]; 28% first-degree relatives of a mutation-negative proband). Subjects were evaluated using ECG, Holter monitoring, signal-averaged ECG, and cardiac magnetic resonance (CMR). Disease progression was defined as the development of a new criterion by the 2010 Task Force criteria (TFC; not “Hamid criteria”) at last follow-up, which was absent at enrollment. Results At first evaluation, 43 (37%) subjects fulfilled ARVD/C diagnosis according to the 2010 TFC. Among the remaining 74 (63%) individuals, 11/37 (30%) subjects with complete reevaluation experienced disease progression during 4.1±2.3 years of follow-up. Electrical progression (n=10 [27%] including ECG 14%, Holter monitoring 11%, signal-averaged ECG 14%) was more frequently observed than structural progression (n=1 [3%] on CMR). All 5/37 (14%) patients with clinical ARVD/C diagnosis at last follow-up had an abnormal ECG or Holter monitor, and the only patient with an abnormal CMR already had an abnormal ECG at enrollment. Conclusion Over a mean follow-up of 4 years, our study showed that (1) almost one-third of at-risk relatives have electrical progression; (2) structural progression is rare; and (3) electrical abnormalities precede detectable structural changes. This information could be valuable in determining family screening protocols.

Objectives To identify the incremental value and optimal role of Cardiac Magnetic Resonance (CMR) imaging in arrhythmic risk stratification of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) associated desmosomal mutation carriers without a prior history of sustained ventricular arrhythmia. Background Risk stratification of ARVD/C mutation carriers is challenging. Methods We included 69 patients (age 27.0 ± 15.3 years, 42% male) harboring ARVD/C associated pathogenic mutations (83% PKP-2) without prior sustained ventricular arrhythmias. Electrocardiography (ECG) and 24-hours Holter monitoring closest to presentation were analyzed for electrical abnormalities as per revised Task Force Criteria. CMR studies were done to identify abnormal cardiac structure and function according to the revised Task Force Criteria. Results Overall, 42 (61%) patients presented with electrical abnormalities based on their ECG and Holter monitor, of whom 20 (48%) had an abnormal CMR. Only 1 (4%) of 27 patients without electrical abnormalities at initial evaluation had an abnormal CMR. Over a mean follow-up of 5.8 ± 4.4 years, 11 (16%) patients experienced a sustained ventricular arrhythmia, exclusively in patients with both electrical abnormalities (ECG and/or Holter) and abnormal CMR. Conclusion Our results suggest that electrical abnormalities on ECG and Holter monitoring precede detectable structural abnormalities in ARVD/C mutation carriers. Therefore, evaluation of cardiac structure and function using CMR is probably not necessary in the absence of baseline electrical abnormalities. Among ARVD/C mutation carriers, the presence of both electrical and CMR abnormalities identifies patients at high risk of events and thus patients who might benefit from prophylactic implantable cardioverter-defibrillator implantation.

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Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver arising from malignant transformation and growth of biliary ductal epithelium. Approximately 50-70 % of CCAs arise at the hilar plate of the biliary tree, which are termed hilar cholangiocarcinoma (HC). Various staging systems are currently employed to classify HCs and determine resectability. Depending on the pre-operative staging, the mainstays of treatment include surgery, chemotherapy, radiation therapy, and photodynamic therapy. Surgical resection offers the only chance for cure of HC and achieving an R0 resection has demonstrated improved overall survival. However, obtaining longitudinal and radial surgical margins that are free of tumor can be difficult and frequently requires extensive resections, particularly for advanced HCs. Pre-operative interventions may be necessary to prepare patients for major hepatic resections, including endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, and portal vein embolization. Multimodal therapy that combines chemotherapy with external beam radiation, stereotactic body radiation therapy, bile duct brachytherapy, and/or photodynamic therapy are all possible strategies for advanced HC prior to resection. Orthotopic liver transplantation is another therapeutic option that can achieve complete extirpation of locally advanced HC in judiciously selected patients following standardized neoadjuvant protocols.

Purpose The aim of this study was to evaluate response of the targeted tumor burden by functional magnetic resonance imaging (MRI) including volumetric diffusion-weighted imaging and volumetric contrast-enhanced MRI (CE-MRI) and its impact on survival in patients with hepatocellular carcinoma treated with intra-arterial therapy (IAT). Materials and Methods This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study included 157 hepatocellular carcinoma lesions in 97 patients (78 men and 19 women; mean age, 64 years) treated with IAT. All patients had pretreatment and 3- to 4-week follow-up MRI with diffusion-weighted imaging and CE-MRI. All lesions 2 cm or larger that were targeted during the first session of IAT were segmented using research software (MR-Oncotreat) to determine targeted tumor burden relative to liver volume (%). Targeted tumor burden was stratified into low (≤10%) or high (>10%). Response using volumetric functional apparent diffusion coefficient (ADC; increase by ≥25%) and CE-MRI (decrease by ≥50% and ≥65% in arterial and venous enhancement [VE], respectively) was assessed in all targeted tumors (range, 1–11) using paired t tests. Kaplan-Meier survival analysis was performed and log-rank test was used to compare pairs of survival curves. Multivariate Cox regression analysis was performed to determine the simultaneous effect of treatment response and tumor burden on survival after adjusting for age, sex, and Child Pugh status. Results There was a significant increase in volumetric ADC (median, 15%; P < 0.001) and a decrease in volumetric arterial enhancement (AE) and VE (median AE, −43% and portal venous phase (PVP), −29%, respectively; P < 0.001) 3 to 4 weeks after treatment in the targeted tumor burden. Multivariable Cox regression demonstrated that both ADC response and low tumor burden were independently associated with greater survival (hazard ratios, 0.53 and 0.55; P values, 0.025 and 0.016, respectively) after adjustment for age, sex, and Child Pugh status. Multivariable Cox regression models demonstrated no statistically significant relationship between AE response and survival after adjusting for tumor burden. However, multivariable Cox regression demonstrated that VE response was associated with greater survival only in those with low tumor burden (hazard ratio, 0.10; P = 0.001), indicating a strong interaction between VE response and tumor burden. Conclusion Quantifying targeted tumor burden is important in predicting patient survival when using functional MRI metrics in assessing treatment response.