A unique cause of coronary obstruction after transcatheter aortic valve replacement.

Delayed coronary obstruction is a rare but often fatal complication of transcatheter aortic valve replacement that can present within 24 hr after the transcatheter aortic valve replacement procedure. We present a case of a 77-year-old woman whose distal left main coronary artery bifurcation became obstructed by an embolized piece of native valve leaflet material 16 hours after the uncomplicated transfemoral implantation of an Edwards Sapien Ultra 23 mm aortic valve, which was successfully treated with the simultaneous kissing stent technique.

Cytoprotection of human endothelial cells from oxidant stress with CDDO derivatives: network analysis of genes responsible for cytoprotection.

AIM: To identify drugs that may reduce the impact of oxidant stress on cell viability. METHODS: Human umbilical vein endothelial cells were treated with 200 nmol/l CDDO-Im (imidazole) and CDDO-Me (methyl) after exposure to menadione and compared to vehicle-treated cells. Cell viability and cytotoxicity were assessed, and gene expression profiling was performed. RESULTS: CDDO-Im was significantly more cytoprotective and less cytotoxic (p < 0.001) than CDDO-Me. Although both provided cytoprotection by induction of gene transcription, CDDO-Im induced more genes. In addition to a higher induction of the key cytoprotective gene heme oxygenase-1 (38.9-fold increase for CDDO-Im and 26.5-fold increase for CDDO-Me), CDDO-Im also induced greater expression of heat shock proteins (5.5-fold increase compared to 2.8-fold for CDDO-Me). CONCLUSIONS: Both compounds showed good induction of heme oxygenase, which largely accounted for their cytoprotective effect. Differences were detected in cytotoxicity at higher doses, indicating that CDDO-Me was more cytotoxic than CDDO-Im. Significant differences were detected in the ability of CDDO-Im and CDDO-Me to affect differential gene transcription. CDDO-Im induced more genes than did CDDO-Me. The source of the differences in gene expression patterns between CDDO-Im and CDDO-Me was not determined but may be important in long-term use of this class of drugs.

Transcatheter mitral valve implantation: Implications of interventional technique and 3D echocardiography for complex valve-in-valve paravalvular leak.

Transcatheter mitral valve replacement (TMVR) has emerged as a feasible alternative to surgical reoperation in failed bioprostheses and rings. Residual mitral regurgitation following TMVR can present as a valve-in-valve paravalvular leak (PVL) and is associated with increased morbidity and mortality. Current therapies for valve-in-valve PVL are limited. We present a case of a symptomatic patient with severe valve-in-valve PVL after TMVR for a previous surgical bioprosthesis leak, who then underwent a second TMVR as a valve-in-valve-in-valve implantation with a 29 mm Edwards® SAPIEN 3 valve via transseptal approach using three-dimensional (3D) echocardiography. This unique case highlights the complexity of this clinical entity and recognizes 3D transesophageal echocardiography as a valuable tool to guide valve-in-valve PVL closures.

Micro-fabricated perforated polymer devices for long-term drug delivery.

Fabrication techniques have been developed to produce a perforated polymer microtube as a drug delivery device. The technique consists of first forming a silicon platform with trenches and alignment marks to hold the tubes for subsequent processing. Photolithography and reactive ion etching with an inductively coupled plasma source were used to fabricate micro holes on the surface of polyimide tubes. Several materials have been used to form the etching mask, including titanium film deposited by e-beam evaporation and SiO(2) and SiN(x) films deposited by high-density plasma chemical vapor deposition (HDPCVD). Three equidistant holes of 20 µm in diameter were fabricated on polyimide tubes (I.D. = 125 µm). The perforated tubes were loaded with ethinyl estradiol and tested for drug release in phosphate buffered saline (pH = 7.1) at 37°C. Zero order release was observed over a period of 30 days with a potential to be extended to 4 years.

Development and characterization of a scalable microperforated device capable of long-term zero order drug release.

A drug delivery system that consists of microperforated polyimide microtubes was developed and characterized. Two groups of polyimide tubes were used. One set consisted of microtubes (I.D. = 125 microm) with 32.9 +/- 1.7 microm size holes. The second set consisted of larger tubes (I.D. = 1000 microm) with 362-542 microm holes. The number of holes was varied between 1 and 3. The small tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE) and the drug release studies were performed in 0.01 M phosphate buffered saline (PBS) (pH 7.1-7.4) at 37.0 +/- 1.0 degrees C for upto 4 weeks. The large tubes were loaded with CV and the drug release was studied in vitro in PBS and also ex vivo in rabbit's vitreous humor. Linear release rates with R(2) > 0.9900 were obtained for all groups with CV and EE. Release rates of 7.8 +/- 2.5, 16.2 +/- 5.5, and 22.5 +/- 6.0 ng/day for CV and 30.1 +/- 5.8 ng/day for EE were obtained for small tubes. For large tubes, a release rate of 10.8 +/- 4.1, 15.8 +/- 4.8 and 22.1 +/- 6.7 microg/day was observed in vitro in PBS and a release rate of 5.8 +/- 1.8 microg/day was observed ex vivo in vitreous humor.

Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction.

AIMS: Heart failure (HF) patients with a mid-range ejection fraction (HFmrEF) are not well characterized. Accordingly, we examined the epidemiology, pathophysiology and clinical outcomes of HF patients with a left ventricular ejection fraction (LVEF) of 40-50%. METHODS AND RESULTS: We identified 168 patients with an LVEF between 40-50% at enrollment into a HF registry, and determined whether LVEF was improved, worsened, or the same compared to a prior LVEF. Three subgroups of HFmrEF patients were identified: HFmrEF improved (prior LVEF <40%); HFmrEF deteriorated (prior LVEF >50%); HFmrEF unchanged (prior LVEF 40-50%). The majority of patients (73%) were HFmrEF improved, 17% were HFmrEF deteriorated, and 10% were HFmrEF unchanged. The demographics of the HFmrEF cohort were heterogeneous, with more coronary artery disease in the HFmrEF improved group and more hypertension and diastolic dysfunction in the HFmrEF deteriorated group. HFmrEF improved patients had significantly (P<0.001) better clinical outcomes relative to matched patients with HF and reduced ejection fraction, and significantly (P<0.01) improved clinical outcomes relative to HFmrEF deteriorated patients, whereas clinical outcomes of the HFmrEF deteriorated subgroup of patients were not significantly different from matched HF patients with preserved ejection fraction. CONCLUSIONS: Patients with a mid-range LVEF are heterogeneous. Obtaining historical information with regard to prior LVEF allows one to identify a distinct pathophysiological substrate and clinical course for HFmrEF patients. Viewed together, these results suggest that in the modern era of HF therapeutics, the use of LVEF to categorize the pathophysiology of HF may be misleading, and argue for establishing a new taxonomy for classifying HF patients.

Evaluation of a perforated drug delivery system in mice for prolonged and constant release of a hydrophilic drug.

A drug delivery system (DDS) consisting of a perforated microtube (polyimide, inside diameter = 1.8 mm, tube length = 20 mm, hole size = 0.15 mm) was characterized in vitro and in vivo for its usefulness for long-term release of hydrophilic drugs at a constant rate. Sodium fluorescein mixed with stearic acid was used as the model drug. The DDS was packed with sodium fluorescein and stearic acid in ratios of 50:50, 40:60, and 25:75, respectively, and in vitro drug release studies were performed in saline. Linear release rates with R (2) > 0.9700 were obtained for all groups. Release rates of 1,077.3 ± 264.6, 342.6 ± 146.4, and 14.4 ± 7.0 µg/day for sodium fluorescein were obtained from the three groups, respectively. After monitoring the in vitro release of fluorescein for 11 days, 7 tubes from the 40:60 group were implanted subcutaneously in each individual mice to study the in vivo release of fluorescein from the tubes by measuring the fluorescein in the urine for 84 days. An initial rapid release during the first 4 days was followed by a near zero order fluorescence from the tubes (R (2) = 0.9870). Following completion of the study, the DDSs were retrieved for histology. Morphological analysis indicated no clinical adverse reaction at the site of device implantation specific to the device. The DDS was found to be biocompatible and capable of long-term constant release of a hydrophilic drug such as sodium fluorescein.

Drug eluting stents and beyond.

The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be developed globally. Hence, there is a need to review the available methodology to control their quality and to understand the delivery of drugs to the lesion. This can be achieved by systematically reviewing the novelties in each type. The article evaluates upcoming drugs, biocompatible coatings, and new concepts. We have also provided the latest update on the three new promising drug eluting stents (DES) - Medtronic's Endeavor, Abbott's Xience, and Conor Medsystem's CoStar. In addition, the article also summarizes other DES in horizon.