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Transcatheter aortic valve replacement (TAVR) is a recommended intervention for selected population with severe aortic stenosis (AS). Bicuspid aortic valve (BAV) anatomy has been categorized as an unfavorable anatomy for TAVR due to multiple considerations as exclusion from randomized trials in addition to the challenging and unpredictable anatomy. The anatomical constraints of BAV include the large anatomy of the annulus, sinus of Valsalva, and aorta (aortopathy), in addition to significant calcifications of the device landing zone. Most commercial transcatheter heart valves (THV) have upper dimension limits of the annulus and area in which the device can be implanted safely without significant oversizing. Myval-XL THVs (Meril Life Sciences Pvt. Ltd., India) are balloon-expandable valves (BEV) that have been developed with two new sizes, 30.5 and 32 mm, aiming to treat patients with large annulus dimensions and that exceed the upper limit of an ordinary device’s sizing matrix. This case series report describes TAVR using the XL-Myval 32 mm THV in three European patients with symptomatic severe bicuspid aortic stenosis with significant calcifications and large annular dimensions exceeding the limits of the other THVs.

Additional file 1: Supplementary Table 1. Criteria used for the literature research across Embase, Medline and Google Scholar. Supplementary Table 2. Summary of CTRCT events, and related genetic variants in studies investigating genes other than HER2. Supplementary Table 3. Top 5 most significantly upregulated and downregulated genes between trastuzumab treated versus nontreated single cancer cells. Supplementary Table 4. Association between serum miR-222-3p and cardiotoxicity.

ObjectivesWe sought to investigate a new angiographic method for aortic regurgitation (AR) severity assessment in the setting of transcatheter aortic valve implantation (TAVI). BackgroundAR after TAVI is common but challenging to quantitate, especially in the cath-lab. MethodsIn 228 patients, AR was quantitated before and after TAVI by echocardiography and by video-densitometric analysis of aortograms. Contrast time-density curves for the aortic root (the reference region) and the left ventricular outflow tract, LVOT were generated. LVOT-AR was calculated as the area under the curve of the LVOT as a fraction of the area under the curve of the reference region. ResultsLVOT-AR was 0.100.08, 0.13 +/- 0.10 and 0.28 +/- 0.14 in none-trace, mild and moderate-severe post-TAVI AR as defined by echocardiography (P 0.17 corresponded to moderate-severe AR on echocardiography (area under the curve=0.84). At follow-up (median, 496 days), patients with LVOT-AR0.17 showed a significant reduction of LV mass index (LVMi; 121 [95-148] vs. 140 [112-169]g/m(2), P=0.009) and the prevalence of LV hypertrophy (LVH; 64 vs. 88%, P=0.001) compared to baseline. In patients with LVOT-AR>0.17, LVMi (149 [121-178] vs. 166 [144-188]g/m(2), P=0.14) and the prevalence of LVH (74 vs. 87%, P=0.23) did not show a significant change. Compared to patients with LVOT-AR0.17, those with LVOT-AR>0.17 had an increased 30-day (16.4% vs. 7.1%, P=0.035) and one year mortality (32.9 vs. 14.2%, log rank P value=0.001; HR: 2.690 [1.461-4.953], P=0.001). ConclusionsLVOT-AR>0.17 corresponds to greater than mild AR as defined by echocardiography and predicts impaired LV reverse remodeling and increased early and midterm mortality after TAVI. (c) 2017 Wiley Periodicals, Inc

Shows microcirculatory changes during weaning attempts. Table S2B. Shows microcirculatory differences at baseline VA-ECMO flow. Table S2C. shows microcirculatory differences between baseline and reduced VA-ECMO flow. Table S3. Shows correlation between microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. Table S4A. Shows comparison of the ROC curves of microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. Table S4B. Shows comparison of the ROC curves of microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. (DOCX 27 kb)

Shows technical overview of the SDF and IDF devices (adapted with permission from van Elteren et al. [19]). (DOCX 12 kb)

Shows microcirculatory changes during weaning attempts. Table S2B. Shows microcirculatory differences at baseline VA-ECMO flow. Table S2C. shows microcirculatory differences between baseline and reduced VA-ECMO flow. Table S3. Shows correlation between microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. Table S4A. Shows comparison of the ROC curves of microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. Table S4B. Shows comparison of the ROC curves of microcirculatory and echocardiographic parameters for the prediction of successful weaning from VA-ECMO. (DOCX 27 kb)

To expand the application of a drug in orally disintegrating tablets, the potential use of beta-cyclodextrin (beta-CyD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) as excipients for the tablets containing dl-alpha-tocopheryl acetate (VE), an oily drug, was evaluated. HP-beta-CyD, not beta-CyD, solubilized VE in water through the formation of higher order of complexes at the molar ratio of 1 : 2 (VE : HP-beta-CyD). When prepared under the optimal preparation conditions, the VE tablets containing lactose and 5% (w/w) of HP-beta-CyD, not beta-CyD, had high hardness more than 4 kg and rapid disintegration within 100 s both in vitro and in vivo. In addition, VE tablets containing lactose and 5% (w/w) of HP-beta-CyD, not beta-CyD, maintained the high hardness and rapid disintegration under the accelerated stability test using different conditions for 4 weeks. Therefore, these results suggest the potential use of HP-beta-CyD, not beta-CyD, as an excipient for orally disintegrating tablets containing VE, an oily drug, in the molding method.

Aim: To investigate interpolymer complexes (IPCs) formation between carbopol and cationic polymers such as chitosan and Eudragit E for oral controlled drug delivery systems. Methodology: The prepared IPCs were investigated using Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Chitosan-carbopol and Eudragit E-carbopol IPCs loaded with diltiazem hydrochloride (DTZ HCl) with different drug:polymer ratios were also prepared. Diltiazem hydrochloride tablets were prepared using polymers alone, physical mixtures of chitosan or Eudragit E with carbopol and the corresponding drug loaded IPCs. In-vitro release studies were carried out in two dissolution media; 0.1 NHCl of pH 1.2 and phosphate buffer of pH 7.4. Results: The dissolution rate of DTZ HCl from the prepared tablets were found to be dependant on the interaction between chitosan or Eudragit E with carbopol in the physical mixture, drug:polymer ratio and pH of the dissolution medium. Tablets prepared using chitosan – carbopol IPC, Eudragit E – carbopol IPC, and Eudragit E – carbopol physical mixture of drug:polymer ratio 1:5 were selected for the in-vivo study using rabbits. The results showed a lower peak plasma concentration and marked prolonged release effect of tablets containing Eudragit E – carbopol IPC and the corresponding physical mixture compared to that of commercial Altiazem tablets. Conclusion: Tablets containing Eudragit E – carbopol or chitosan – carbopol physical mixtures showed prolonged drug release compared to that containing the corresponding IPCs, Furthermore, Eudragit E- carbopol matrix tablets showed slower drug release than that of chitosan – carbopol.

Background: The wall motion score index (WMSI) is a surrogate for left ventricular ejection fraction (LV-EF), which becomes unreliable in poor echo windows. The value of contrast LV opacification (LVO) for WMSI assessment is not well known. Objectives: We sought to compare interobserver agreement for WMSI and the correlation between the LVO-WMSI and LV-EF using two-dimensional second harmonic (SH) and LVO echocardiography. Methods: The study comprised 100 consecutive patients (57 +/- 13 years, 85% males). Two independent physicians assessed LV segmental quality and wall motion for both the SH and LVO studies according to a 17-segment model. Systolic wall motion was defined as: normokinesia, hypokinesia (systolic inward endocardial motion < 7 mm), akinesia, and dyskinesia. LV-EF was assessed from the LVO images according to the biplane modified Simpson's method. Results: Of the 1,700 analyzed segments, 453 (26.6%) were poorly visualized with SH imaging, and 173 (10.2%) with LVO (P < 0.0001). The two observers agreed on segmental wall motion score in 1,299 segments (agreement 76%, Kappa 0.60) with SH imaging and in 1,491 segments (agreement 88%, Kappa 0.78) with LVO. Interobserver correlation (r2) was 0.86 for the SH-WMSI and 0.93 for the LVO-WMSI. The limits-of-agreement for interobserver LVO-WMSI (mean difference -1.0% +/- 6.8%, agreement -14.6%, 12.6%) was lower than that for SH-WMSI (mean difference -2.3% +/- 10.1%, agreement -22.5, 17.9). The LVO-WMSI correlated well with LV-EF (r2 = 0.71). LV-EF could be estimated according to the formula 1.01 - 0.32 x WMSI. Conclusion: Echo-contrast improves interobserver agreement for wall motion scoring and the WMSI. The LVO-imaged WMSI correlates well with LV-EF. (Echocardiography 2011;28:575-581).

Background: Patients with aortic stenosis (AS) should undergo aortic valve replacement (AVR) before irreversible LV dysfunction has developed. Assessment of long-axis left ventricular (LV) function may assist in proper timing of AVR. Objectives: To assess serial changes in long-axis LV function before and after AVR in patients with severe AS and preserved LV ejection fraction. Methods: The study comprised 27 consecutive patients (mean age 64.9 +/- 11.7 years, 15 males) with symptomatic severe AS, scheduled for AVR. Seventeen subjects without known cardiac disease, matched for age, gender, LV ejection fraction and cardiovascular risk factors, served as a control group. Long-axis LV function assessment was done with tissue Doppler imaging at 3 weeks, 6 months, and 12 months after AVR. Results: Mean aortic valve area in the AS group was 0.70 +/- 0.24 cm2. Pre-AVR peak systolic mitral annular velocities were significantly lower compared to controls (6.7 +/- 1.5 vs. 8.9 +/- 2.0 cm/s, P < 0.05). Post-AVR peak systolic mitral annular velocities improved to 9.1 +/- 2.9 at 3 weeks, 8.6 +/- 2.7 at 6 months, and 8.1 +/- 1.7 cm/s at 12 months (P < 0.05). Improvements were seen over the whole range of pre-AVR peak systolic mitral annular velocities. Patients with improved Sm after AVR (defined as >= 10% compared to baseline values) did not differ in baseline characteristics as compared to those who did not improve. Conclusions: In patients with severe AS and preserved LV ejection fraction, abnormal systolic mitral annular velocities improve after AVR, independent of the pre-AVR value. (Echocardiography 2010;27:1177-1181).

PURPOSE. Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties during echocardiography. METHODS. A total of 19 patients with typical features of LHON aged 42+/-13 years (10 males) were included. Their results were compared to 19 age- and gender-matched healthy controls. Aortic stiffness index was calculated from the echocardiographically derived aortic diameters and the clinical blood pressure data. RESULTS. In this patient population, the point mutation was present in 3460G>A position in five cases, in 11778G>A position in five cases, and in 14484T>C position in nine patients. Diastolic aortic diameter (26.0+/-2.5 mm vs 28.4+/-4.1 mm, p< 0.05) and aortic stiffness index (5.1+/-2.6 vs 12.0+/-7.9, p< 0.05) were significantly increased in LHON patients compared to controls. CONCLUSIONS. Aortic stiffness can be increased in LHON disease, but further studies are warranted to confirm these findings in a larger LHON patient population with a more reliable method focusing on the pathophysiologic background.

Dobutamine stress magnetic resonance imaging is considered the superior stress modality to detect wall motion abnormalities. In this report we demonstrate the strengths of a newly developed stress modality: dobutamine stress contrast-enhanced real-time three-dimensional echocardiography. This stress modality may become a competitor of stress magnetic resonance imaging allowing fast acquisition and an unlimited number of left ventricular cross sections. Unfortunately, at the moment adequate imaging with stress real-time three-dimensional echocardiography is only possible in a minority of cardiac patients.