MR Imaging Enables Real-Time Monitoring of In Vitro Electrolytic Ablation of Hepatocellular Carcinoma.

PURPOSE: To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. MATERIALS AND METHODS: Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. RESULTS: Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. CONCLUSIONS: T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.

Endovascular treatment of surgical mesoportal and portosystemic shunt dysfunction in pediatric patients.

BACKGROUND: Published data describing the endovascular treatment of dysfunctional mesoportal and portosystemic shunts in the pediatric population are limited. OBJECTIVE: We sought to describe the treatment and follow-up of such shunts managed by interventional radiology at a single pediatric hospital. We hypothesized that stenotic and occluded pediatric portosystemic and mesoportal shunts can be maintained patent by interventional radiology in the moderate term. MATERIALS AND METHODS: We conducted a single-center retrospective study at a tertiary pediatric hospital. We included children with surgical mesoportal (meso-Rex) or portosystemic (mesocaval, splenorenal or splenocaval) shunts treated with attempted angioplasty or stenting from 2010 to 2018. Technical success was defined as catheterization and intervention upon the shunt with venographic evidence of flow improvement. The primary outcome variables were shunt patency at 1 month, 6 months, 12 months and 24 months post-procedure and freedom from reintervention. RESULTS: Twenty pediatric patients (11 boys, 9 girls; mean age 8.25 years, range 1.3-17 years) met inclusion criteria. Fifty-two interventions (primary and reintervention) on 13 splenorenal, 3 meso-Rex, 2 mesocaval and 2 splenocaval shunts were performed because of evidence of shunt failure, including gastrointestinal bleeding, hypersplenism, or radiographic evidence of a flow defect. The 11 stenotic shunts were treated with 100% technical success, while the remaining 9 occluded shunts were treated with 66.7% technical success. The mean number of reinterventions was 1.9 (standard deviation [SD] = 3.1) per child, which did not differ between stenotic and occluded shunts (P=0.24). Primary patency at 1-month, 6-month, 12-month and 24-months follow-up visits was 17/17 (100%), 10/16 (62.5%), 7/15 (46.7%) and 4/10 (40%), respectively. However, 100% of shunts were either primary patent or primary-assisted patent by endovascular reintervention. There were no cases of shunt occlusion following initial technical success. Finally, the median freedom from reintervention duration was 387 days (SD=821 days). CONCLUSION: Dysfunctional portosystemic surgical shunts are effectively managed by endovascular methods. While many shunts require reintervention, combined primary patency and assisted primary patency rates are excellent.

Persistence in Coil-Embolized Pulmonary Arteriovenous Malformations with Feeding Artery Diameters of 3 mm or Less: A Retrospective Single-Center Observational Study.

PURPOSE: To assess persistence in coil-embolized pulmonary arteriovenous malformations (PAVMs) with feeding artery diameters ≤ 3 mm. MATERIALS AND METHODS: Fifty-eight patients (21 male, 37 female; mean age, 43 y; range, 13-71 y) with 141 simple-type PAVMs treated from 2004 to 2014 were analyzed retrospectively. Inclusion criteria were one or more PAVMs with feeding artery diameters ≤ 3 mm ("small PAVMs"), treatment with coil embolization, and presence of a follow-up chest computed tomographic (CT) angiogram at approximately 6 months. Feeding artery diameter, total coil length, and coil nest-to-PAVM sac distance were measured on arteriographic images. Coil packing density was estimated. Persistence was defined as less than 70% reduction in PAVM sac size and was assessed for each PAVM with respect to previous arteriogram or CT angiogram. Each variable was statistically tested for association with persistence. RESULTS: On follow-up CT arteriography, 111 of 141 PAVMs (79%) showed a 70% or greater reduction in size of the sac and were deemed not persistent. The remaining 30 (21%) with unchanged or minimally reduced sac sizes were classified as persistent. Feeding artery diameter, coil size, quantity of coils, shape of coils, coil nest length, compaction, and visible packing density did not affect persistence, but coil nest-to-sac distance was directly correlated with persistence (P < .006). This result held true even with nest-to-sac distances of less than 1 cm. CONCLUSIONS: Small PAVMs have a high persistence rate after coil embolotherapy. Most previously described risk factors for PAVM persistence do not seem to apply to these PAVMs, with the exception of coil nest-to-sac distance.

Associations of Sarcopenia and Body Composition Measures With Mortality After Transcatheter Aortic Valve Replacement.

BACKGROUND: Frailty associates with worse outcomes after transcatheter aortic valve replacement (TAVR). Sarcopenia underlies frailty, but the association between a comprehensive assessment of sarcopenia-muscle mass, strength, and performance-and outcomes after TAVR has not been examined. METHODS: From a multicenter prospective registry of patients with symptomatic severe aortic stenosis undergoing TAVR, 445 who had a preprocedure computed tomography and clinical assessment of frailty were included. Cross-sectional muscle (psoas and paraspinal) areas were measured on computed tomography and indexed to height. Gait speed and handgrip strength were obtained, and patients were dichotomized into fast versus slow; strong versus weak; and normal versus low muscle mass. As measures of body composition, cross-sectional fat (subcutaneous and visceral) was measured and indexed to height. RESULTS: The frequency of patients who were slow, weak, and had low muscle mass was 56%, 59%, and 42%, respectively. Among the 3 components of sarcopenia, only slower gait speed (muscle performance) was independently associated with increased post-TAVR mortality (adjusted hazard ratio, 1.12 per 0.1 m/s decrease [95% CI, 1.04-1.21]; P=0.004; adjusted hazard ratio, 1.38 per 1 SD decrease [95% CI, 1.11-1.72]; P=0.004). Meeting multiple sarcopenia criteria was not associated with higher mortality risk than fewer. Lower indexed visceral fat area (adjusted hazard ratio, 1.48 per 1 SD decrease [95% CI, 1.15-1.89]; P=0.002) was associated with mortality but indexed subcutaneous fat was not. Death occurred in 169 (38%) patients. CONCLUSIONS: Among patients with symptomatic severe aortic stenosis and comprehensive sarcopenia and body composition phenotyping, gait speed was the only sarcopenia measure associated with post-TAVR mortality. Lower visceral fat was also associated with increased risk pointing to an obesity paradox also observed in other patient populations. These findings reinforce the clinical utility of gait speed as a measure of risk and a potential target for adjunctive interventions alongside TAVR to optimize clinical outcomes.

Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis.

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01-1.77, P=0.043). cTnT and NT-proBNP each risk stratified patients with moderate/severe LVH (P<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45-3.00, P<0.001) and elevated NT-proBNP (aHR, 1.46; 95% CI 1.00-2.11, P=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (P=0.15). Conclusions Elevations in circulating cTnT and NT-proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT-proBNP predict post-transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.

Global Longitudinal Strain and Biomarkers of Cardiac Damage and Stress as Predictors of Outcomes After Transcatheter Aortic Valve Implantation.

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (P<0.001 for each). aGLS <15% was associated with increased mortality in univariable analysis (P=0.009), but, in a model with both biomarkers, aGLS, and clinical covariates included, aGLS was not associated with mortality; elevation in each biomarker was associated with an increased hazard of mortality (adjusted hazard ratio, >2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Intravascular ultrasound is a key diagnostic tool in subclavian vein varicosity.

Varicose veins of the neck are far less common than lower extremity varicosities. Often, neck varicosities can be a sign of a more central venous obstruction. Here, we describe a patient with no risk factors for central venous obstruction who presented with a recurrent left subclavian vein (LSV) varicosity causing significant pain and discomfort that was recalcitrant to repeated phlebectomy. Venography revealed a dilated LSV with no significant venographic stenosis in the LSV or brachiocephalic vein. Intravascular ultrasound subsequently revealed a culprit hypertrophied valve that was successfully treated with valvuloplasty, resulting in durable resolution of the patient's symptoms, suggesting that intravascular ultrasound was essential in the diagnosis and treatment of this hypertrophied valve.

Electrolytic ablation enables cancer cell targeting through pH modulation.

Minimally invasive ablation strategies enable locoregional treatment of tumors. One such strategy, electrolytic ablation, functions through the local delivery of direct current without thermal effects, facilitating enhanced precision. However, the clinical application of electrolytic ablation is limited by an incompletely characterized mechanism of action. Here we show that acid and base production at the electrodes precipitates local pH changes causing the rapid cell death that underlies macroscopic tumor necrosis at pH > 10.6 or < 4.8. The extent of cell death can be modulated by altering the local buffering capacity and antioxidant availability. These data demonstrate that electrolytic ablation is distinguished from other ablation strategies via its ability to induce cellular necrosis by directly altering the tumor microenvironment. These findings may enable further development of electrolytic ablation as a curative therapy for primary, early stage tumors.