Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity

Objective- This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. Methods- Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. Results- Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 �g/ml) nor native LDL (100 �g/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 �M), and MnTBAP (a free radical scavenger, 50��M). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2 .- levels were determined in IMA versus CA VSMC. Conclusions- Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects

The “Evolving” Role of Intravascular Imaging in Myocardial Infarction With Nonobstructive Coronary Arteries

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Age- and Lesion-Related Comorbidity Burden Among US Adults With Congenital Heart Disease: A Population-Based Study.

Background As patients with congenital heart disease (CHD) are living longer, understanding the comorbidities they develop as they age is increasingly important. However, there are no published population-based estimates of the comorbidity burden among the US adult patients with CHD. Methods and Results Using the IBM MarketScan commercial claims database from 2010 to 2016, we identified adults aged ≥18 years with CHD and 2 full years of continuous enrollment. These were frequency matched with adults without CHD within categories jointly defined by age, sex, and dates of enrollment in the database. A total of 40 127 patients with CHD met the inclusion criteria (mean [SD] age, 36.8 [14.6] years; and 48.2% were women). Adults with CHD were nearly twice as likely to have any comorbidity than those without CHD (P<0.001). After adjusting for covariates, patients with CHD had a higher prevalence risk ratio for "previously recognized to be common in CHD" (risk ratio, 9.41; 95% CI, 7.99-11.1), "other cardiovascular" (risk ratio, 1.73; 95% CI, 1.66-1.80), and "noncardiovascular" (risk ratio, 1.47; 95% CI, 1.41-1.52) comorbidities. After adjusting for covariates and considering interaction with age, patients with severe CHD had higher risks of previously recognized to be common in CHD and lower risks of other cardiovascular comorbidities than age-stratified patients with nonsevere CHD. For noncardiovascular comorbidities, the risk was higher among patients with severe than nonsevere CHD before, but not after, the age of 40 years. Conclusions Our data underscore the unique clinical needs of adults with CHD compared with their peers. Clinicians caring for CHD may want to use a multidisciplinary approach, including building close collaborations with internists and specialists, to help provide appropriate care for the highly prevalent noncardiovascular comorbidities

Looking towards the future: patient-specific computational modeling to optimize outcomes for transcatheter mitral valve repair

Severe mitral valve regurgitation (MR) is a heart valve disease that progresses to end-stage congestive heart failure and death if left untreated. Surgical repair or replacement of the mitral valve (MV) remains the gold standard for treatment of severe MR, with repair techniques aiming to restore the native geometry of the MV. However, patients with extensive co-morbidities may be ineligible for surgical intervention. With the emergence of transcatheter MV repair (TMVR) treatment paradigms for MR will evolve. The longer-term outcomes of TMVR and its effectiveness compared to surgical repair remain unknown given the differing patient eligibility for either treatment at this time. Advances in computational modeling will elucidate answers to these questions, employing techniques such as finite element method and fluid structure interactions. Use of clinical imaging will permit patient-specific MV models to be created with high accuracy and replicate MV pathophysiology. It is anticipated that TMVR technology will gradually expand to treat lower-risk patient groups, thus pre-procedural computational modeling will play a crucial role guiding clinicians towards the optimal intervention. Additionally, concerted efforts to create MV models will establish atlases of pathologies and biomechanics profiles which could delineate which patient populations would best benefit from specific surgical vs. TMVR options. In this review, we describe recent literature on MV computational modeling, its relevance to MV repair techniques, and future directions for translational application of computational modeling for treatment of MR

Transcatheter valve implantation for right atrium‐to‐right ventricle conduit obstruction or regurgitation after modified Björk–fontan procedure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136276/1/ccd26648_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136276/2/ccd26648.pd

Acute and midterm outcomes of the post-approval MELODY Registry: a multicentre registry of transcatheter pulmonary valve implantation

AIMS The post-approval MELODY Registry aimed to obtain multicentre registry data after transcatheter pulmonary valve implantation (TPVI) with the Melody™ valve (Medtronic plc.) in a large-scale cohort of patients with congenital heart disease (CHD). METHODS AND RESULTS Retrospective analysis of multicentre registry data after TPVI with the Melody™ valve. Eight hundred and forty-five patients (mean age: 21.0 ± 11.1 years) underwent TPVI in 42 centres between December 2006 and September 2013 and were followed-up for a median of 5.9 years (range: 0-11.0 years). The composite endpoint of TPVI-related events during follow-up (i.e. death, reoperation, or reintervention >48 h after TPVI) showed an incidence rate of 4.2% per person per year [95% confidence interval (CI) 3.7-4.9]. Transcatheter pulmonary valve implantation infective endocarditis (I.E.) showed an incidence rate of 2.3% per person per year (95% CI 1.9-2.8) and resulted in significant morbidity and in nine deaths. In multivariable Cox proportional hazard models, the invasively measured residual right ventricle (RV)-to-pulmonary artery (PA) pressure gradient (per 5 mmHg) was associated with the risk of the composite endpoint (adjusted hazard ratio: 1.21, 95% CI 1.12-1.30; P 2 improved significantly from 36 [interquartile range (IQR) 24-47] to 12 (IQR 7-17) mmHg and 47 to 1%, respectively (P < 0.001 for each). CONCLUSION The post-approval MELODY Registry confirms the efficacy of TPVI with the Melody™ valve in a large-scale cohort of CHD patients. The residual invasively measured RV-to-PA pressure gradient may serve as a target for further improvement in the composite endpoint and TPVI I.E. However, TPVI I.E. remains a significant concern causing significant morbidity and mortality

Pulmonary arterial hypertension associated with congenital heart disease

Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD), with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD. The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH-CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges. This article gives an overview of the demographics, pathophysiology and treatment of PAH-CHD and focuses on individuals with Down's syndrome as an important and challenging patient group

Dual Arterial Access for Stenting of Aortic Coarctation in Patients with Near-Total Descending Aortic Interruption

Endovascular stenting is a recognized treatment strategy for the treatment of coarctation of aorta (COA) in adults. The aortic coarctation is usually crossed retrogradely from the descending aorta via the femoral approach. We report three patients who ha

Pre-closure of Large-Sized Arterial Access Sites in Adults Undergoing Transcatheter Structural Interventions

INTRODUCTION: Patients undergoing structural heart interventions often require large-sized sheath insertion into femoral arteries and veins. Clinical outcome data on the use of suture-mediated devices for large femoral arterial access in structural heart interventions is limited. We assessed the efficacy of the Perclose™ (Abbott Vascular Devices, Santa Clara, CA, USA) suture-mediated device using the pre-closure technique in achieving hemostasis in femoral arterial access sites following large sheath insertion (≥8 Fr). METHODS: One hundred consecutive patients underwent 101 femoral artery access sites closures with the Perclose device using the pre-closure technique. Sixty-two percent of the patients were male and their mean (SD) age was 52 (±26) years. All patients received heparin. RESULTS: Mean arterial access site sheath diameter was 13 ± 2 Fr. Immediate hemostasis was achieved in 96/101 (96%) procedures (≤2 min). Two patients (2%) had access site-related complications requiring further interventions. On clinical follow up [mean (SD) follow-up of 24 (±12) months and median follow-up of 8.5 months], no complications were seen in the arterial access sites. CONCLUSION: Pre-closure of large-size femoral arterial access sheath sites using the suture-mediated Perclose device is efficacious in achieving rapid hemostasis in patients undergoing structural interventions. On 1-year follow-up, there were no arterial access site complications requiring further investigations or interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40119-014-0034-7) contains supplementary material, which is available to authorized users