Publications

No abstract is provided for this article.

Myhre syndrome is a rare, distinctive syndrome due to specific gain‐of‐function mutations in SMAD4 . The characteristic phenotype includes short stature, dysmorphic facial features, hearing loss, laryngotracheal anomalies, arthropathy, radiographic defects, intellectual disability, and a more recently appreciated spectrum of cardiovascular defects with a striking fibroproliferative response to surgical intervention. We report four newly described patients with typical features of Myhre syndrome who had (i) a mildly narrow descending aorta and restrictive cardiomyopathy; (ii) recurrent pericardial and pleural effusions; (iii) a large persistent ductus arteriosus with juxtaductal aortic coarctation; and (iv) restrictive pericardial disease requiring pericardiectomy. Additional information is provided about a fifth previously reported patient with fatal pericardial disease. A literature review of the cardiovascular features of Myhre syndrome was performed on 54 total patients, all with a SMAD4 mutation. Seventy percent had a cardiovascular abnormality including congenital heart defects (63%), pericardial disease (17%), restrictive cardiomyopathy (9%), and systemic hypertension (15%). Pericarditis and restrictive cardiomyopathy are associated with high mortality (three patients each among 10 deaths); one patient with restrictive cardiomyopathy also had epicarditis. Cardiomyopathy and pericardial abnormalities distinguish Myhre syndrome from other disorders caused by mutations in the TGF‐β signaling cascade (Marfan, Loeys–Dietz, or Shprintzen–Goldberg syndromes). We hypothesize that the expanded spectrum of cardiovascular abnormalities relates to the ability of the SMAD4 protein to integrate diverse signaling pathways, including canonical TGF‐β, BMP, and Activin signaling. The co‐occurrence of congenital and acquired phenotypes demonstrates that the gene product of SMAD4 is required for both developmental and postnatal cardiovascular homeostasis. © 2016 Wiley Periodicals, Inc.

No abstract is provided for this article.

Objective To evaluate effect of strut protrusion (SP) on wall shear stress (WSS) and neointimal growth (NG) 1 and 5 year after implantation of Absorb scaffold. Method 8 patients were selected from Absorb Cohort B. After 3-dimensional reconstruction of coronaries, WSS was quantified using Newtonian steady flow simulation (Figure). At 1-year neointimal thickness (NT) was measured by optical coherence tomography and correlated to WSS and SP post-procedure. Results Median SP was 112.9 (90.8, 133.1) μm. A logarithmic (log) inverse relationship between SP and post-procedure WSS (r=−0.425 p<0.001 correlation coefficients range: −0.143 to −0.553) was observed whereas a correlation between baseline log transformed WSS and NT (r=−0.451 p<0.001 correlation coefficients range: −0.140 to −0.662) was documented at 1 year. Mixed effects analysis between baseline log transformed WSS and NT at follow up yielded a slope of 30 μm/ln Pascal (Pa) and a y-intercept of 98 μm. As result of NG, flow area decreased from 6.91 (6.53, 7.48) mm2 post-implantation to 5.65 (5.47, 6.02) mm2 at 1 year (p=0.01) and to 5.75±1.37 mm2 at 5 years (p=0.024). Vessel surface with low WSS (<1 Pa) decreased from post-procedure (42%) to 1 year (35.9%) and 5 years (15.2%) (p-overall<0.0001). Conclusion SP disturbs laminar flow, creates region of low WSS that is mechanistically associated with NG and lumen area reduction. This observation would suggest thin strut with effective embedment would reduce NG and improve WSS towards physiological values.

This study explores the safety and efficacy of thin strut MeRes100 sirolimus-eluting bioresorbable vascular scaffold (BRS) in patients with de novo coronary artery lesions.In interventional cardiology, the emergence of BRS technology is catalyzing the next paradigm shift.The MeRes-1 Extend was a multicenter, prospective, single-arm, open-label study enrolling 64 patients in Spain, Macedonia, Brazil, South Africa, Malaysia, and Indonesia. The safety endpoint was major adverse cardiac events (MACE) which composed of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). The imaging efficacy endpoint was mean in-scaffold late lumen loss (LLL) evaluated by quantitative coronary angiography (QCA). Optical coherence tomography (OCT) imaging was performed at baseline and 6-month follow-up.A total of 69 target lesions were identified in 64 enrolled patients (mean age 58.30 ± 9.02 years). Of the treated lesions, 49 (71.01%) lesions were of type B2/C. Procedural and device success was achieved in 64 and 62 patients, respectively. At 2-year follow-up, MACE was reported in one patient (1.61%) in the form of ID-TLR. There was no case of MI, cardiac death or scaffold thrombosis through 2-year. In a subset of 32 patients, paired QCA showed mean in-scaffold LLL of 0.18 ± 0.31 mm at 6-month follow-up. In a subset of 21 patients, OCT revealed 97.95 ± 3.69% strut coverage with mean scaffold area of 7.56 ± 1.79 mm2 and no evidence of strut malapposition.The clinical and imaging outcomes of MeRes-1 Extend trial demonstrated favorable safety and efficacy of MeRes100 sirolimus-eluting BRS in patients with de novo coronary artery lesions.

No abstract is provided for this article.

Activation of the transcription factor signal transducer and activator of transcription (STAT)‐4 is critical for the differentiation of T‐helper 1 cells/type‐1 cytotoxic T‐cells and the production of interferon (IFN)‐γ. Expression of STAT4, phospho‐STAT4, IFN‐γ and T‐box expressed in T‐cells (T‐bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)‐derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV 1 ) 59±16% predicted), 14 smokers with normal lung function (FEV 1 106±12% pred) and 12 nonsmoking subjects (FEV 1 111±14% pred), was examined by immunohistochemistry and immunocytochemistry. In bronchial biopsies of COPD patients, the number of submucosal phospho‐STAT4+ cells was increased (240 (22–406) versus 125 (0–492) versus 29 (0–511) cells·mm −2 ) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho‐STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN‐γ+ cells. Similar results were seen in BAL (2.8 (0.2–5.9) versus 1.03 (0.09–1.6) versus 0.69 (0–2.3) lymphocytes·mL −1 ×10 3 ). In all smokers who underwent lavage, phospho‐STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNγ+ lymphocytes. T‐bet expression was not altered in bronchial biopsies and BAL‐derived lymphocytes between the three groups. In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T‐helper 1 cell/type‐1 cytotoxic T‐cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.

Unstable angina is an acute coronary syndrome associated with substantial short- and medium-term morbidity and mortality.1 The understanding of the pathogenesis of this syndrome has been based largely on postmortem studies of coronary arteries2 and supported by indirect evidence of coronary thrombosis in relation to the syndrome.3–5 Because directional coronary atherectomy is unique in extracting intact atheromatous tissue during coronary recanalization, it may facilitate the study of the processes taking place in the vessel in different coronary syndromes. In the present study the histopathologic characteristics of atherectomy samples retrieved in 93 patients with stable or unstable angina pectoris were compared and related to different clinical variables.

No abstract is provided for this article.