Publications

Objectives This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR). Background PVR after TAVR is challenging to quantify, especially during the procedure. Methods Post-replacement aortograms in 135 TAVR recipients were analyzed offline by videodensitometry to measure the ratio of the time-resolved contrast density in the left ventricular outflow tract to that in the aortic root (videodensitometric aortic regurgitation [VD-AR]). CMR was performed within an interval of ≤30 days (11 ± 6 days) after the procedure. Results The average CMR-RF was 6.7 ± 7.0% whereas the average VD-AR was 7.0 ± 7.0%. The correlation between VD-AR and CMR-RF was substantial (r = 0.78, p < 0.001). On receiver-operating characteristic curves, a VD-AR ≥10% corresponded to >mild PVR as defined by CMR-RF (area under the curve: 0.94; p < 0.001; sensitivity 100%, specificity 83%), whereas a VD-AR ≥25% corresponded to moderate-to-severe PVR (area under the curve: 0.99; p = 0.004; sensitivity 100%, specificity 98%). Intraobserver reproducibility was excellent for both techniques (for CMR-RF, intraclass correlation coefficient: 0.91, p < 0.001; for VD-AR intraclass correlation coefficient: 0.93, p < 0.001). The difference on rerating was –0.04 ± 7.9% for CMR-RF and –0.40 ± 6.8% for VD-AR. Conclusions The angiographic VD-AR provides a surrogate assessment of PVR severity after TAVR that correlates well with the CMR-RF.

Bronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells.To study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity.Levels of ezrin were measured in exhaled breath condensate (EBC) and serum in patients with asthma and BAL fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells. Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells.Ezrin levels were decreased in asthmatic EBC (92.7 ± 34.99 vs. 150.5 ± 10.22 pg/ml, P < 0.0001) and serum (700.7 ± 55.59 vs. 279.2 ± 25.83 pg/ml, P < 0.0001) compared with normal subjects. Levels were much lower in uncontrolled (P < 0.001) and partly controlled patients (P < 0.01) compared with well-controlled subjects. EBC and serum ezrin levels correlated with lung function in patients with asthma and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced downregulation of ezrin expression in primary bronchial epithelial cells was significantly attenuated by the Janus tyrosine kinase 2 inhibitor, TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces, and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of "asthmatic" mice and negatively correlated with BALF IL-13 level.Ezrin downregulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control.

Purpose: Adenosine exerts a variety of actions that may attenuate many of the proposed mechanisms of reperfusion-mediated injury, including inhibition of neutrophil-mediated microvascular obstruction. Yet, attempts to achieve cardioprotection with administration of adenosine at reperfusion have yielded conflicting results in both pre-clinical and clinical settings. We sought to determine the effects of adenosine on infarct size (IS) and no-reflow in an appropriate translational porcine model, taking into account the predicted terms for efficacious intervention (i.e., prolonged intracoronary infusion starting just prior to reperfusion). Methods: Thirty-six open-chest swine of either sex were subjected to a 45-min left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Animals received either intracoronary adenosine (50 μg/kg/min; n=15) infused for 2 h starting 5 min prior to reperfusion or an equal volume of saline (controls; n=21). The area-at-risk was delineated with Evans Blue, IS was determined histochemically with triphenyltetrazolium staining and no-reflow measured with thioflavin S staining. Results: Adenosine infusion significantly increased coronary blood flow throughout the 2-h reperfusion period compared with controls (p<0.001), with a maximum fourfold increase relative to baseline at 30 min of reperfusion (397±62% vs. 217±18% in controls; p<0.001). In contrast, adenosine did not affect systemic hemodynamic variables. Area-at-risk was similar between groups (p=NS). Administration of adenosine resulted in a significant reduction in IS (% area-at-risk; 46±4%) compared with controls (59±3%; p=0.02). Likewise, no-reflow (% IS) was significantly reduced in the adenosine-treated group (26±6%) compared to controls (49±6%; p=0.03). Conclusion: High and prolonged intracoronary adenosine infusion during early reperfusion limits infarct size and no-reflow in a porcine preparation of ST-segment elevation myocardial infarction. Further studies are warranted to confirm this effect, especially, when considering that there is no successful clinical pharmacological treatment for prevention of reperfusion-mediated injury at present.

Background Long‐term outcomes of diabetic patients suffering from ST‐segment elevation myocardial infarction (STEMI) and treated with second‐generation drug‐eluting stent have been scarcely evaluated. The aim of this posthoc subanalysis of the EXAMINATION trial was to compare 5‐year outcomes according to the presence of diabetes mellitus. Methods From a total of 1,497 patients included in the trial, 258 were diabetics ( n = 137, received everolimus‐eluting stent (EES) and n = 121 bare‐metal stent (BMS); whereas 1,239 were nondiabetics ( n = 613 treated with EES and n = 626 with BMS). Patient‐oriented combined endpoint (POCE) defined as all‐cause death, any MI or any revascularization, and other clinical parameters were collected up to 5‐years. All results were adjusted for various potential confounders. Results At 5‐years, patients with diabetes showed similar rates of POCE between diabetics treated with EES and those treated with BMS (32.8% vs. 32.2%; p = 0.88). However, rates of TLR were significantly lower in the EES group (4.4% vs. 9.9%; HR 0.52 (0.29–0.94); P = 0.03). In non‐diabetics, the use of EES was associated with a significant improvement in all‐clinical parameters except for MI rate: POCE: [10.0% vs. 12.6%; HR 0.78(0.62–0.98); P = 0.038], all cause death: [7.0% vs. 12.1%; HR 0.62(0.42–0.90); P = 0.014], and [TLR: 4.2 vs. 6.7; HR 0.60 (0.37–0.98); P = 0.04]. Overall, diabetics showed higher rate of POCE at 5‐years (32.6% vs. 21.5% in nondiabetics HR1.45[1.03–2.04];p = 0.03) driven by increased rates of MI and the need for revascularization that occurred in coronary segments remote from target lesions [2.7% vs. 1.1%; HR: 2.27 (1.12–5.23); P = 0.02 and 14% vs. 6.2%; HR: 2.11 (1.38–3.22); P = 0.001, respectively]. Conclusions Diabetics had worse clinical outcomes than nondiabetics after STEMI mainly due to atherosclerosis progression. At 5‐years, the treatment with EES did not reduce the rate of POCE in diabetics but reduced the need for revascularization compared with BMS.

No abstract is provided for this article.

It has been 40 years since percutaneous coronary intervention (PCI) was introduced into the clinical setting. Over these years significant advances in device technology and the invention of new therapeutic strategies have broadened its applications in the clinical arena, rendering this treatment the first-line therapy for patients with obstructive coronary artery disease. The evolution of PCI would not have been possible without intravascular imaging which provided unique insights about coronary artery pathology, enabled evaluation of vessel wall response following PCI and allowed meticulous evaluation of the advantages and limitations of emerging devices. This review article appraises the role of intravascular imaging in the evolution of PCI, summarises the findings of invasive imaging studies that examined the efficacy of new therapies and endovascular devices, presents the evidence that supports its use in current clinical practice and discusses its future potential in PCI.

No abstract is provided for this article.

No abstract is provided for this article.

Pretreatment of bovine tracheal smooth muscle (BTSM) with histamine (1–100 μ M , 1 h) induced a concentration‐dependent desensitization of the contractile response to subsequently administered histamine, with a reduction of the maximum response of 72±8% ( n =5) following pre‐exposure to 100 μ M histamine. In contrast, concentration‐response curves to the muscarinic agonist, methacholine were not affected following histamine pretreatment, indicating a homologous desensitization. Furthermore, concentration‐response curves to NaF, a G‐protein activator, were not altered following histamine pre‐incubation. The histamine H 1 ‐receptor (H 1 R) desensitization could be antagonized by mepyramine (an H 1 ‐receptor antagonist, 1 μ M ) but not by cimetidine (an H 2 ‐receptor antagonist, 10 μ M ), indicating that the desensitization occurred via stimulation of histamine H 1 ‐receptors, without evidence for the involvement of histamine H 2 ‐receptors. Indomethacin (10 μ M ) did not block the H 1 R desensitization, suggesting no involvement of prostaglandins. Furthermore, histamine pre‐incubation in calcium free medium still induced a functional uncoupling of H 1 R. GF 109203X, a protein kinase C (PKC) inhibitor, and H‐7, a non‐selective kinase inhibitor, did not antagonize the homologous H 1 R desensitization. The steady‐state level of H 1 R mRNA, assessed by Northern blot analysis, was not affected by prolonged histamine exposure (100 μ M , 0.5, 1, 2, 4, 16 and 24 h). These results suggest that histamine induces desensitization of the H 1 R at the level of the receptor protein, which involves a mechanism independent of PKC, PKA, PKG and calcium influx, suggesting the involvement of a receptor‐specific kinase. British Journal of Pharmacology (1998) 123 , 984–990; doi: 10.1038/sj.bjp.0701697

No abstract is provided for this article.

Objectives We sought to investigate a new angiographic method for aortic regurgitation (AR) severity assessment in the setting of transcatheter aortic valve implantation (TAVI). Background AR after TAVI is common but challenging to quantitate, especially in the cath‐lab. Methods In 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. Results LVOT‐AR was 0.10 ± 0.08, 0.13 ± 0.10 and 0.28 ± 0.14 in none‐trace, mild and moderate‐severe post‐TAVI AR as defined by echocardiography ( P &lt; 0.001) and a cutpoint of &gt;0.17 corresponded to moderate‐severe AR on echocardiography (area under the curve = 0.84). At follow‐up (median, 496 days), patients with LVOT‐AR ≤ 0.17 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 &gt; 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‐AR ≤ 0.17, those with LVOT‐AR &gt; 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). Conclusions LVOT‐AR &gt; 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. © 2017 Wiley Periodicals, Inc.

Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent.In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m2 in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23+/-0.22 versus [minus]0.58+/-0.30 mm, P=0.02), (2) reduction in NH (1.48+/-0.58, 2.46+/-1.25, and 2.36+/-1.13 mm2, P<0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH.The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.