Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.

A simplified method to correct saturation of arterial input function for cardiac magnetic resonance first-pass perfusion imaging: validation with simultaneously acquired PET.

BACKGROUND: First-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on 13N-ammonia positron emission tomography (PET). METHODS: Sixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 mCi of 13N-ammonia. The MRI perfusion acquisition started simultaneously with the start of the PET acquisition after the injection of a 0.075 mmol/kg gadolinium contrast agent. Cardiac stress imaging was initiated after the administration of regadenoson 20 s prior to PET-MRI scanning. The saturation part of the MRI AIF data was modeled as a gamma variate curve, which was then estimated for a true AIF by minimizing a cost function according to various boundary conditions. A standard AHA 16-segment model was used for comparative analysis of absolute MBF from PET and MRI. RESULTS: Overall, there were 256 segments in 16 patients, mean resting perfusion for PET was 1.06 ± 0.34 ml/min/g and 1.04 ± 0.30 ml/min/g for MRI (P = 0.05), whereas mean stress perfusion for PET was 2.00 ± 0.74 ml/min/g and 2.12 ± 0.76 ml/min/g for MRI (P < 0.01). Linear regression analysis in MBF revealed strong correlation (r = 0.91, slope = 0.96, P < 0.001) between PET and MRI. Myocardial perfusion reserve, calculated from the ratio of stress MBF over resting MBF, also showed a strong correlation between MRI and PET measurements (r = 0.82, slope = 0.81, P < 0.001). CONCLUSION: The results demonstrated the feasibility of the simplified AIF estimation method for the accurate quantification of MBF by MRI with single sequence and single contrast injection. The MRI MBF correlated strongly with PET MBF obtained simultaneously. This post-processing technique will allow easy transformation of clinical perfusion imaging data into quantitative information.

Normalized Subendocardial Myocardial Attenuation on Coronary Computed Tomography Angiography Predicts Postoperative Adverse Cardiovascular Events: Coronary CTA VISION Substudy.

BACKGROUND: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery. METHODS: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUBnormalized, and TRANSnormalized, respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction. RESULTS: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUBnormalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUBnormalized, patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANSnormalized, as a continuous variable, was also found to be a predictor of MACE (P=0.027). CONCLUSIONS: Our study demonstrates that SUBnormalized and TRANSnormalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Myocardial Cut-off Sign is a Sensitive and Specific Cardiac Computed Tomography and Magnetic Resonance Imaging Sign to Distinguish Left Ventricular Pseudoaneurysms From True Aneurysms.

PURPOSE: The purpose of this study was to describe the myocardial cut-off sign, assess its ability to distinguish left ventricular pseudoaneurysms (LV PSAs) from true aneurysms (LVAs), and compare its performance with other imaging findings and quantitative measurements used to differentiate LV PSAs from LVAs. MATERIALS AND METHODS: This retrospective single-center study identified patients with preoperative cardiac computed tomography (CT) or magnetic resonance imaging (MRI) and surgically confirmed LVAs or LV PSAs over a 10-year period. Seventeen LV PSAs (11 MRI, 6 CT) and 18 LVAs (10 MRI, 8 CT) were included. The myocardial cut-off sign was objectively a >50% decrease in aneurysm sac wall thickness measured at 1 cm from the aneurysmal neck (measurements at 2 cm were also assessed) and subjectively an abrupt "cut-off" of myocardium for the aneurysm sac for PSA compared with a gradual tapering of sac wall thickness for LVA. Two radiologists independently evaluated images for the subjective presence of this sign. RESULTS: The myocardial cut-off sign was 91% sensitive and 97% specific when measured 1 cm from the aneurysm neck. When measured at 2 cm from the neck, the sign was 100% sensitive and 69% specific. Subjective analysis of whether the myocardium appeared "cut-off" was 94% to 100% sensitive and 78% to 94% specific with excellent agreement for both PSA (κ=0.94) and LVA (κ=0.83). CONCLUSIONS: The myocardial cut-off sign on cardiac CT and MRI is a sensitive and specific finding of LV PSA. Specificity is improved with objective measurements compared with subjective assessment (97% vs. 78% to 94%). This sign may help radiologists distinguish between LV PSAs and LVAs.

Role of cardiovascular magnetic resonance in early detection and treatment of cardiac dysfunction in oncology patients.

The purpose of this review is to provide an overview of the essential role that cardiovascular magnetic resonance (CMR) has in the field of cardio-oncology. Recent findings: CMR has been increasingly used for early identification of cancer therapy related cardiac dysfunction (CTRCD) due to its precision in detecting subtle changes in cardiac function and for myocardial tissue characterization. Summary: CMR is able to identify subclinical CTRCD in patients receiving potentially cardiotoxic chemotherapy and guide initiation of cardio protective therapy. Multiparametric analysis with myocardial strain, tissue characterization play a critical role in understanding important clinical questions in cardio-oncology.

CC Chemokine Receptor 5 Targeted Nanoparticles Imaging the Progression and Regression of Atherosclerosis Using Positron Emission Tomography/Computed Tomography.

Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 in vivo, we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). In vivo pharmacokinetic evaluation through 64Cu radiolabeling showed extended blood circulation of 64Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. In vivo positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE-/-) showed that the three 64Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE-/- mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of 64Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of ex vivo human plaque specimens warrant further investigation for atherosclerosis prognosis.

Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome.

BACKGROUND: Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function. METHODS/RESULTS: Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of 15O-water and 1-11C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging. LV function and cardiac high-energy phosphate metabolism were examined via echocardiography and 31P magnetic resonance spectroscopy, respectively. Myocardial glucose extraction fraction (21 ± 14% vs 10 ± 8%, P = .03) and glucose utilization (828.0 ± 470.0 vs 393.2 ± 361.0 µmol·g-1·min-1, P = .02) were significantly higher in BTHS vs Control. Myocardial FA extraction fraction (31 ± 7% vs 41 ± 6%, P < .002) and uptake (0.25 ± 0.04 vs 0.29 ± 0.03 mL·g-1·min-1, P < .002) were significantly lower in BTHS vs Control. Altered myocardial metabolism was associated with lower cardiac function in BTHS. CONCLUSIONS: Myocardial substrate metabolism is altered and may contribute to LV dysfunction in BTHS. Clinical Trials #: NCT01625663.

Medical 3D Printing Cost-Savings in Orthopedic and Maxillofacial Surgery: Cost Analysis of Operating Room Time Saved with 3D Printed Anatomic Models and Surgical Guides.

RATIONALE AND OBJECTIVE: Three-dimensional (3D) printed anatomic models and surgical guides have been shown to reduce operative time. The purpose of this study was to generate an economic analysis of the cost-saving potential of 3D printed anatomic models and surgical guides in orthopedic and maxillofacial surgical applications. MATERIALS AND METHODS: A targeted literature search identified operating room cost-per-minute and studies that quantified time saved using 3D printed constructs. Studies that reported operative time differences due to 3D printed anatomic models or surgical guides were reviewed and cataloged. A mean of $62 per operating room minute (range of $22-$133 per minute) was used as the reference standard for operating room time cost. Different financial scenarios were modeled with the provided cost-per-minute of operating room time (using high, mean, and low values) and mean time saved using 3D printed constructs. RESULTS: Seven studies using 3D printed anatomic models in surgical care demonstrated a mean 62 minutes ($3720/case saved from reduced time) of time saved, and 25 studies of 3D printed surgical guides demonstrated a mean 23 minutes time saved ($1488/case saved from reduced time). An estimated 63 models or guides per year (or 1.2/week) were predicted to be the minimum number to breakeven and account for annual fixed costs. CONCLUSION: Based on the literature-based financial analyses, medical 3D printing appears to reduce operating room costs secondary to shortening procedure times. While resource-intensive, 3D printed constructs used in patients' operative care provides considerable downstream value to health systems.

3D Printing Custom Bioactive and Absorbable Surgical Screws, Pins, and Bone Plates for Localized Drug Delivery.

Additive manufacturing has great potential for personalized medicine in osseous fixation surgery, including maxillofacial and orthopedic applications. The purpose of this study was to demonstrate 3D printing methods for the fabrication of patient-specific fixation implants that allow for localized drug delivery. 3D printing was used to fabricate gentamicin (GS) and methotrexate (MTX)-loaded fixation devices, including screws, pins, and bone plates. Scaffolds with different infill ratios of polylactic acid (PLA), both without drugs and impregnated with GS and MTX, were printed into cylindrical and rectangular-shaped constructs for compressive and flexural strength mechanical testing, respectively. Bland PLA constructs showed significantly higher flexural strength when printed in a Y axis at 100% infill compared to other axes and infill ratios; however, there was no significant difference in flexural strength between other axes and infill ratios. GS and MTX-impregnated constructs had significantly lower flexural and compressive strength as compared to the bland PLA constructs. GS-impregnated implants demonstrated bacterial inhibition in plate cultures. Similarly, MTX-impregnated implants demonstrated a cytotoxic effect in osteosarcoma assays. This proof of concept work shows the potential of developing 3D printed screws and plating materials with the requisite mechanical properties and orientations. Drug-impregnated implants were technically successful and had an anti-bacterial and chemotherapeutic effect, but drug addition significantly decreased the flexural and compressive strengths of the custom implants.

3D Printed Antibiotic and Chemotherapeutic Eluting Catheters for Potential Use in Interventional Radiology: In Vitro Proof of Concept Study.

RATIONALE AND OBJECTIVES: Additive manufacturing may be used as a form of personalized medicine in interventional radiology by allowing for the creation of customized bioactive constructs such as catheters that can act as a form of localized drug delivery. The purpose of the present in vitro study was to use three-dimensional (3D) printing to construct bioactive-laden bioabsorbable catheters impregnated with antibiotics and chemotherapeutics. MATERIALS AND METHODS: Polylactic acid bioplastic pellets were coated with the powdered bioactive compounds gentamicin sulfate (GS) or methotrexate (MTX) to incorporate these drugs into the 3D printed constructs. The pellets were then extruded into drug-impregnated filament for fused deposition modeling 3D printing. Computer-aided design files were generated in the shapes of 14-F catheters. Scanning electron microscope imaging was used to visualize the presence of the additive powders on the surface of the printed constructs. Elution profiles were run on the antibiotic-laden catheter and MTX-laden catheters. Antibiotic-laden catheters were tested on bacterial broth and plate cultures. RESULTS: Both GS and MTX catheter constructs had sustained drug release up to the 5-day limit of testing. The 3D printed GS-enhanced catheters inhibited all bacterial growth in broth cultures and had an average zone of inhibition of 858 ± 118 mm2 on bacterial plates, whereas control catheters had no effect. CONCLUSION: The 3D printing manufacturing method to create instruments in percutaneous procedures is feasible. Further in vivo studies will substantiate these findings.

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

BACKGROUND: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. METHODS: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. RESULTS: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. CONCLUSIONS: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

3D Printing is a Transformative Technology in Congenital Heart Disease.

Survival in congenital heart disease has steadily improved since 1938, when Dr. Robert Gross successfully ligated for the first time a patent ductus arteriosus in a 7-year-old child. To continue the gains made over the past 80 years, transformative changes with broad impact are needed in management of congenital heart disease. Three-dimensional printing is an emerging technology that is fundamentally affecting patient care, research, trainee education, and interactions among medical teams, patients, and caregivers. This paper first reviews key clinical cases where the technology has affected patient care. It then discusses 3-dimensional printing in trainee education. Thereafter, the role of this technology in communication with multidisciplinary teams, patients, and caregivers is described. Finally, the paper reviews translational technologies on the horizon that promise to take this nascent field even further.

Anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR.

PURPOSE: To report the anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR. MATERIALS AND METHODS: Retrospective review of the medical records between February 2001 and February 2016 was performed. To identify patients, radiological reports were queried for "Scimitar" or "partial anomalous pulmonary venous return." Patients with radiological findings of Scimitar syndrome were included. Patients without cross-sectional imaging were excluded. Patients' demographics, radiologic images, and medical notes were reviewed. Two radiologists re-read the available imaging studies. Images were reviewed for Scimitar syndrome confirmation, number and location of Scimitar vein drainage, number of lobes drained by the Scimitar vein, and right pulmonary artery and lung hypoplasia. In addition, the number of pulmonary veins draining into the left atrium, left sided anomalous pulmonary veins, congenital heart disease, aortic arch anomalies, cardiac dextroposition, right ventricular enlargement, pulmonary artery enlargement, and elevated QP:QS ratios were identified. Other associated anomalies including the presence of an anomalous feeding artery and pulmonary sequestration, abnormal lobar pattern, localized bronchiectasis, horseshoe lung, accessory diaphragm, diaphragmatic hernia, vertebral anomalies, and genitourinary tract anomalies were reviewed. RESULTS: Sixteen patients (3 males, 13 females; mean age 39.5 years, range 14 days-72 years) with confirmed Scimitar syndrome on CT and MR imaging were identified. The Scimitar vein drained to the infra-diaphragmatic inferior vena cava (IVC) in ten patients and to the supra-diaphragmatic IVC in six patients. The most common associated anomalies were right ventricle enlargement (93.3%), variant lobar pattern of the right lung (92.9%), enlarged pulmonary arteries (60%), and cardiac dextroposition (50%). CONCLUSION: Recognizing the radiologic characteristics and anatomical associations of Scimitar syndrome is important as features of the primary condition and associated anomalies may have implications in surgical management.

Cardiac Positron Emission Tomography-Magnetic Resonance Imaging: Current Status and Future Directions.

Simultaneous acquisition positron emission tomography-magnetic resonance imaging (PET-MRI) has the ability to combine anatomic information derived from cardiac MRI with quantitative capabilities of cardiac PET and MRI and the promise of molecular imaging by specific PET tracers. This combination of cardiac PET and MRI delivers a robust and comprehensive clinical examination. It has the potential to assess various cardiovascular conditions, including assessment of myocardial ischemia, infarction, and function, as well as specific characterization of inflammatory and infiltrative heart diseases such as cardiac sarcoid and amyloid. It also offers fascinating possibilities in imaging other cardiovascular-related disease states, such as tumor imaging and vascular imaging. In this review, we begin with a general overview of the potentials of PET-MRI in cardiovascular imaging, followed by a discussion of the technical challenges unique to cardiovascular PET-MRI. We then discuss PET-MRI in various cardiovascular disease imaging applications. Potential limitations of PET-MRI and future directions are also considered.

Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

Heterogeneity of systolic dysfunction in patients with severe aortic stenosis and preserved ejection fraction.

BACKGROUND AND AIM: Left ventricular (LV) systolic strain has been shown to be an early marker of LV dysfunction in patients with severe aortic stenosis (AS) despite preserved ejection fraction (EF). Echocardiography has provided useful data on regional LV strain patterns, but is not as sensitive as magnetic resonance imaging (MRI). No prior studies have used MRI-based strain analysis to characterize regional three-dimensional strain in patients with severe AS. METHODS: Twelve patients with severe AS and preserved EF underwent MRI-based multiparametric strain analysis. Circumferential and longitudinal strain values were calculated at individual points throughout the LV and analyzed in 12 discrete regions. Strain values were compared to a database of normal controls. RESULTS: Compared to control patients, circumferential strain in AS patients was significantly reduced at the base (P = 0.002), mid (P = 0.042), and inferior walls (P < 0.001). Longitudinal strain was significantly reduced at the base (P < 0.001), mid (P < 0.001), anterior (P < 0.001), and septal (P < 0.001) walls. Among patients with AS, there was heterogeneity in the location and severity of abnormalities in circumferential and longitudinal strains despite the presence of a preserved EF and lack of prior myocardial infarction. CONCLUSIONS: LV systolic strain is significantly impaired in patients with AS and preserved EF compared to healthy volunteers. Abnormalities in circumferential and longitudinal strains were heterogeneously distributed across the LV of patients with AS, allowing us to identify sentinel regions that may reflect the earliest signs of developing LV dysfunction.