Bioprosthetic Aortic Valve Thrombosis: Definitions, Clinical Impact, and Management: A State-of-the-Art Review.

Bioprosthetic aortic valve thrombosis is frequently detected after transcatheter and surgical aortic valve replacement due to advances in cardiac computed tomography angiography technology and standardized surveillance protocols in low-surgical-risk transcatheter aortic valve replacement trials. However, evidence is limited concerning whether subclinical leaflet thrombosis leads to clinical adverse events or premature structural valve deterioration. Furthermore, there may be net harm in the form of bleeding from aggressive antithrombotic treatment in patients with subclinical leaflet thrombosis. This review will discuss the incidence, mechanisms, diagnosis, and optimal management of bioprosthetic aortic valve thrombosis after transcatheter aortic valve replacement and bioprosthetic surgical aortic valve replacement.

Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.

Diabetes is accompanied by secretion of pro-atherosclerotic exosomes from vascular smooth muscle cells.

BACKGROUND: Atherosclerosis is a common co-morbidity of type 2 diabetes mellitus. Monocyte recruitment by an activated endothelium and the pro-inflammatory activity of the resulting macrophages are critical components of atherosclerosis. Exosomal transfer of microRNAs has emerged as a paracrine signaling mechanism regulating atherosclerotic plaque development. MicroRNAs-221 and -222 (miR-221/222) are elevated in vascular smooth muscle cells (VSMCs) of diabetic patients. We hypothesized that the transfer of miR-221/222 via VSMC-derived exosomes from diabetic sources (DVEs) promotes increased vascular inflammation and atherosclerotic plaque development. METHODS: Exosomes were obtained from VSMCs, following exposure to non-targeting or miR-221/-222 siRNA (-KD), isolated from diabetic (DVEs) and non-diabetic (NVEs) sources and their miR-221/-222 content was measured using droplet digital PCR (ddPCR). Expression of adhesion molecules and the adhesion of monocytes was measured following exposure to DVEs and NVEs. Macrophage phenotype following exposure to DVEs was determined by measuring mRNA markers and secreted cytokines. Age-matched apolipoprotein-E-deficient mice null (ApoE-/-) mice were maintained on Western diet for 6 weeks and received injections of saline, NVEs, NVE-KDs, DVEs or DVE-KDs every other day. Atherosclerotic plaque formation was measured using Oil Red Oil staining. RESULTS: Exposure of human umbilical vein and coronary artery endothelial cells to DVEs, but not NVEs, NVE-KDs, or DVE-KDs promoted increased intercellular adhesion molecule-1 expression and monocyte adhesion. DVEs but not NVEs, NVE-KDs, or DVE-KDs also promoted pro-inflammatory polarization of human monocytes in a miR-221/222 dependent manner. Finally, intravenous administration of DVEs, but not NVEs, resulted in a significant increase in atherosclerotic plaque development. CONCLUSION: These data identify a novel paracrine signaling pathway that promotes the cardiovascular complications of diabetes mellitus.

Optimal timing and diagnostic adequacy of hepatocyte phase imaging with gadoxetate-enhanced liver MRI.

RATIONALE AND OBJECTIVES: To evaluate clinical and imaging features associated with adequacy of the hepatocyte phase (HP) in gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI) in patients without chronic liver disease (CLD). MATERIALS AND METHODS: This was a retrospective institutional review board-approved study of 97 patients who underwent liver MRI examinations with gadoxetate disodium and had no history of CLD. Available late dynamic and HP sequences (3-20 minutes postinjection) were independently analyzed by four radiologists for perceived image adequacy and level of biliary enhancement. Signal intensity ratios (SIRs) of liver/inferior vena cava (IVC), liver/spleen, and liver/muscle were measured. The Spearman ρ and receiver operating characteristic analyses were performed correlating various factors with HP adequacy. A rule for predicting HP adequacy was also derived and tested to determine whether overall examination time could be shortened. RESULTS: A visually adequate HP was observed in 12% of subjects by 10 minutes, 80% by 15 minutes, and 93% by 20 minutes. An SIRliver/IVC > 1.8 was the imaging feature that had the strongest correlation with an adequate HP (ρ = 0.813, P < .001), and was more predictive of adequacy of the HP than the time postinjection (ρ = 0.5, P < .001). The time at which an adequate HP was first observed did not correlate with any tested demographic or laboratory values. Stopping imaging when an SIRliver/IVC > 1.8 would have successfully reduced mean postcontrast time to 15:39 ± 4:02 from 20:00 (P < .001), although maintaining HP adequacy. CONCLUSIONS: Most patients without CLD undergoing gadoxetate-enhanced liver MRI achieve adequate HP at 20 minutes. However, a shorter postcontrast stopping time can be used in most patients.

Diagnostic medical radiation in inflammatory bowel disease: how to limit risk and maximize benefit.

Diagnosis and management of inflammatory bowel disease (IBD) requires repeat diagnostic imaging for monitoring of disease activity. Recent evidence has suggested that patients with IBD are at increased risk of radiation exposure from repeat imaging. The aim of this article was to highlight risks associated with increasing radiation exposure and identify alternatives to minimize exposure. The increasing use of computed tomography (CT) in both Crohn's disease and ulcerative colitis has brought additional benefits to guiding management through non-invasive measures. However, the massive increase in use of CT scans poses a risk of exposing patients with IBD to high levels of diagnostic medical radiation. High levels of diagnostic medical radiation are associated with an increased risk of malignancy in several studies. Numerous studies have identified particular risk factors in IBD associated with high levels of diagnostic medical radiation which are also associated with a more severe disease course. Imaging techniques such as magnetic resonance enterography, ultrasound, small bowel follow through, and capsule endoscopy are alternatives to CT scans as they do not utilize radiation. Gastroenterologists managing patients with IBD, particularly Crohn's disease, should be aware of the increased risk of high cumulative doses of radiation exposure, particularly from CT scanning. Alternative forms of imaging should be carefully considered when evaluating patients, in particularly those with identifiable risk factors for an aggressive disease course.

Assessment of safety, accuracy, and human CD34+ cell retention after intramyocardial injections with a helical needle catheter in a porcine model.

OBJECTIVES: Assess accuracy of Helix injections via fluoroscopic-mapping and evaluate delivery safety. BACKGROUND: Percutaneous intramyocardial-delivery of agents must be safe and accurate; retention is also important. A delivery system (Helical Infusion/Morph Guide-Catheter, Biocardia Inc) has been developed to improve maneuverability and stability of catheter-needle-myocardium intersection. METHODS: Accuracy and safety: 12 swine underwent LV and coronary angiography via 8F sheath. Targeted delivery was assigned into LAD, LCX, or RCA. System was advanced into LV and 6 targeted intramyocardial dye injections (5 mm apart) delivered using fluoroscopy. After euthanization, hearts underwent gross and histologic evaluation. Retention was assessed by iron-oxide and fluorochrome labeled CD34+ cells. Cells were injected into 6 swine using same techniques. Delivery system was advanced into LV, and injections delivered using fluoroscopy. Euthanization was performed at 2 hr and hearts formalin fixed. MRI was performed on 6 treated hearts and 4 untreated controls. Blinded analysis performed by 2 radiologists. Two treated hearts underwent immunohistological analysis. RESULTS: Accuracy and safety evaluation: 71/72 injections (98.6%) were within prespecified zone; 7/72 (9.7%) less than 5 mm apart. No adverse events occurred. MRI-presence of iron-oxide labeled CD34+ cells were correctly identified in 95% (19/20) of imaged injections. Anti-CD34+ antibody staining and fluorescence microscopy confirmed CD34+ cells in myocardium. Histology confirmed cell viability at fixation. CONCLUSIONS: Helix system was accurate and safe. Retention of CD34+ cells was confirmed by MRI and immunohistology. Further preclinical studies are needed to characterize retention over time and quantify efficiency. Studies are needed to confirm accuracy, safety, and retention in humans.

Left ventricular accessory chamber: a case report and review of the literature.

Congenital left ventricular out-pouching, consisting of left ventricular aneurysms, left ventricle diverticulae, and double-chambered left ventricle, is a rare cardiac malformation. Criteria to differentiate between left ventricular aneurysm and diverticulum are defined. Reports of left ventricular accessory chamber in the medical literature are rare. In this article, we present a case of left ventricular accessory chamber diagnosed during the late prenatal period. Review of the literature, imaging modalities used for differentiation of the nature of this lesion, and management plan are discussed.

Ultrasound imaging of carotid artery stenosis: application of the Society of Radiologists in Ultrasound Consensus Criteria to a Single Institution Clinical Practice.

Carotid duplex Doppler ultrasound (CDDU) is increasingly used for the evaluation of internal carotid artery (ICA) stenosis. In CDDU, velocity measurements are used to estimate the degree of ICA stenosis. Traditionally, radiologists have relied on institutional experience and published research when interpreting CDDU. In 2003, a consensus committee of experts convened as the Society of Radiologists in Ultrasound Consensus Committee and proposed standard criteria for grading ICA stenosis including the use of peak systolic velocity (PSV) of greater than 230 cm/s for assigning ICA stenosis of greater than 70%. The purpose of this study was to evaluate the accuracy of the Society of Radiologists in Ultrasound Consensus Criteria in classifying carotid stenoses. This study shows the following: (1) that the criterion of PSV of greater than 230 cm/s for angiographic stenosis of greater than 70% performs as predicted by the consensus committee, with sensitivity of 95.3% (95% confidence interval [CI], 0.89-0.99) and specificity of 84.4% (95% CI, 0.80-0.88); (2) using Pearson correlations, there is no statistical difference found between the correlation of PSV with angiography (0.825 [95% CI, 0.792-0.853]), end diastolic velocity with angiography (0.762 [95% CI, 0.718-0.799]), and the ICA/common carotid artery (CCA) systolic ratio with angiography (0.766 [95% CI, 0.723-0.802]). The correlation of the ICA/CCA diastolic ratio with angiography (0.643 [95% CI, 0.584-0.696]) is less predictive at a 95% confidence interval than the other 3 velocity-based variables, and (3) when the 4 velocity-based variables are taken in pairs (eg, PSV and end diastolic velocity), there is no pair that shows statistically significant improvement in performance. Peak systolic velocity in combination with other variables does show a slight trend toward superior performance.