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1.
Ann Thorac Surg ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794742

RESUMO

BACKGROUND: Minimally invasive mitral valve surgery requires femoral artery cannulation for extracorporeal circulation, predominantly performed through surgical cut-down. Surgical groin incision is frequently associated with complications such as seroma and infection. We evaluated the safety and efficacy of a percutaneous plug-based large-bore vascular closure device (VCD) for femoral artery closure in minimally invasive mitral valve surgery. METHODS: A single-center prospective study comparing patients undergoing minimally invasive mitral valve surgery with femoral cannulation performed either through surgical cut-down or percutaneously with access site closure using a plug-based VCD (MANTA, Teleflex/Essential Medical Inc., Malvern, Pennsylvania, USA). RESULTS: During 2016 to 2018 a total of 268 (147 surgical cut-down, 121 VCD) patients underwent minimally invasive mitral valve surgery with femoral arterial cannulation of catheters sized 19-F or 21-F. Propensity score-matching resulted in 109 matched pairs. In both the overall series and the propensity-matched cohort, VCD patients had a significantly higher incidence of Valve Academic Research Consortium (VARC)-2 major access site vascular complications (overall cohort: 0 vs. 4.1%, p=0.013, propensity score-matched cohort: 0 vs. 4.6%, p=0.024). Bleeding did not occur in any group. In the overall series, surgical cut-down patients had a higher incidence of seroma (10.9% vs 0%, p<0.001). Infection and seroma did not occur in the VCD group. CONCLUSIONS: Percutaneous femoral artery cannulation using a novel plug-based VCD in minimally invasive mitral valve surgery eliminates traditional complications frequently seen with surgical cut-down with no femoral access site seroma and infection though at the expense of an increased risk for vascular complications.

2.
J Mol Cell Cardiol ; 137: 1-8, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31533023

RESUMO

AIMS: The microsomal triglyceride transport protein (MTTP) is critical for assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins and is most abundant in the liver and intestine. Surprisingly, MTTP is also expressed in the heart. Here we tested the functional relevance of cardiac MTTP expression. MATERIALS AND METHODS: We combined clinical studies, advanced expression analysis of human heart biopsies and analyses in genetically modified mice lacking cardiac expression of the MTTP-A isoform of MTTP. RESULTS: Our results indicate that lower cardiac MTTP expression in humans is associated with structural and perfusion abnormalities in patients with ischemic heart disease. MTTP-A deficiency in mice heart does not affect total MTTP expression, activity or lipid concentration in the heart. Despite this, MTTP-A deficient mice displayed impaired cardiac function after a myocardial infarction. Expression analysis of MTTP indicates that MTTP expression is linked to cardiac function and responses in the heart. CONCLUSIONS: Our results indicate that MTTP may play an important role for the heart function in conjunction to ischemic events.

3.
J Am Coll Cardiol ; 74(1): 26-33, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31272548

RESUMO

BACKGROUND: Contemporary data on loss in life expectancy after aortic valve replacement (AVR) are scarce, particularly in younger patients. OBJECTIVES: The purpose of this national, observational cohort study was to analyze long-term relative survival and estimated loss in life expectancy after AVR. METHODS: The study included 23,528 patients who underwent primary surgical AVR with or without concomitant coronary artery bypass grafting in Sweden between 1995 and 2013 from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register. Individual level linking with other national health-data registers was performed to obtain baseline characteristics and vital status. The expected survival from the general Swedish population matched by age, sex, and year of surgery was obtained from the Human Mortality Database. The relative survival was used as an estimate of cause-specific mortality. Flexible parametric models based on relative survival were used to estimate the loss in life expectancy. RESULTS: The mean follow-up was 6.8 years. The 19-year observed, expected, and relative survival was 21%, 34%, and 63% (95% confidence interval [CI]: 59% to 67%), respectively. The loss in life expectancy was 1.9 years (95% CI: 1.2 to 2.6 years) in the total study population. The estimated loss in life expectancy increased with younger age: 0.4 years (95% CI: 0.3 to 0.5 years) versus 4.4 years (95% CI: 1.5 to 7.2 years) in patients ≥80 and <50 years of age, respectively. There was no difference in loss in life expectancy between men and women. CONCLUSIONS: This study found a shorter life expectancy in patients after AVR compared with the general population. The estimated loss in life expectancy was substantial, and increased with younger age. These results provide important information to quantify disease burden after AVR, and are relevant for clinicians counseling patients before and after AVR. (HeAlth-data Register sTudies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).

4.
BMJ Open ; 9(5): e029109, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31061061

RESUMO

OBJECTIVE: Blood type A antigen on porcine aortic bioprostheses might initiate an immune reaction leading to an increased frequency of structural valve deterioration in patients with blood type B or O. The aim was to analyse the association between ABO blood type and porcine bioprosthetic aortic valve degeneration. DESIGN: Observational nationwide cohort study. SETTING: Swedish population-based study. PARTICIPANTS: Adult patients (n=3417) who underwent surgical aortic valve replacement and received porcine bioprosthetic aortic valves between 1995 and 2012 from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register. The study database was enriched with information from other national registers. EXPOSURE: The patients were categorised into type A/AB and type B/O blood groups. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was aortic valve reoperation, and secondary outcomes were heart failure and all-cause mortality. We report risk estimates that account for the competing risk of death. RESULTS: In total, 3417 patients were identified: 1724 (50.5%) with blood type A/AB and 1693 (49.5%) with blood type B/O. Both groups had similar baseline characteristics. The cumulative incidence of aortic valve reoperation was 3.4% (95% CI 2.5% to 4.4%) and 3.6% (95% CI 2.6% to 4.6%) in the type B/O and the A/AB group, respectively, at 15 years of follow-up (absolute risk difference: -0.2% (95% CI -1.5% to 1.2%)). There was no significantly increased risk for aortic valve reoperation in patients with blood type B/O compared with type A/AB (HR 0.95, 95% CI 0.62 to 1.45). There was no significant difference in absolute or relative risk of heart failure or death between the groups. CONCLUSIONS: We found no significant association between patient blood type and clinical manifestations of structural valve deterioration following porcine aortic valve replacement. Our findings suggest that it is safe to use porcine bioprosthetic valves without consideration of ABO blood type in the recipient. TRIAL REGISTRATION NUMBER: NCT02276950.

5.
Int J Mol Sci ; 20(6)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934548

RESUMO

Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.


Assuntos
Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Autofagia , Calcinose/patologia , Regulação para Cima , Insuficiência da Valva Aórtica/patologia , Sobrevivência Celular , Humanos , Lisossomos/metabolismo
6.
Ann Thorac Surg ; 108(3): 770-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30953648

RESUMO

BACKGROUND: Aortic dissection type A requires immediate surgery. In general surgery populations, patients operated on during weekends have higher mortality rates compared with patients whose operations occur on weekdays. The weekend effect in aortic dissection type A has not been studied in detail. METHODS: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) registry includes data for 1,159 patients who underwent type A dissection surgery at 8 Nordic centers during 2005 to 2014. This study is based on data relating to surgery conducted during weekdays versus weekends and starting between 8:00 am and 8:00 pm ("daytime") versus from 8:00 pm to 8:00 am ("nighttime"), as well as time from symptoms, admittance, and diagnosis to surgery. The influence of timing of surgery on the 30-day mortality rate was assessed using logistic regression analysis. RESULTS: The 30-day mortality was 18% (204 of 1,159), with no difference in mortality between surgery performed on weekdays (17% [150 of 889]) and on weekends (20% [54 of 270], p = 0.45), or during nighttime (19% [87 of 467]) versus daytime (17% [117 of 680], p = 0.54). Time from symptoms to surgery (median 7.0 hours vs 6.5 hours, p = 0.31) did not differ between patients who survived and those who died at 30 days. Multivariable regression analysis of risk factors for 30-day mortality showed no weekend effect (odds ratio, 1.04; 95% confidence interval, 60.67 to 1.60; p = 0.875), but nighttime surgery was a risk factor (odds ratio, 2.43; 95% confidence interval, 1.29 to 4.56; p = 0.006). CONCLUSIONS: The 30-day mortality in surgical repair of aortic dissection type A was not significantly affected by timing of surgery during weekends versus weekdays. Nighttime surgery seems to predict increased 30-day mortality, after correction for other risk factors.

7.
Int J Cardiol ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30482443

RESUMO

BACKGROUND: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. METHODS: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. RESULTS: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24-1.52, p = 6.9 × 10-10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31-1.79) compared to those with CAD (OR 1.27; 95%CI 1.12-1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88-0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27-1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95-1.02). CONCLUSIONS: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.

8.
Nat Genet ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30455415

RESUMO

Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)1-3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype.

9.
Atheroscler Suppl ; 35: e6-e13, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30172576

RESUMO

Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm. Aortic endothelial cells were isolated from aortic tissue of patients with thoracic aortic aneurysm and healthy donors. Gene expression of Notch and related BMP and WNT/ß-catenin pathways was estimated by qPCR; WNT/ß-catenin signaling was studied by TCF-luciferase reporter. To study the stress-response the cells were subjected to laminar shear stress and the expression of corresponding genes was estimated by qPCR. Analyses of mRNA expression of Notch genes, Notch target genes and Notch related pathways showed that endothelial cells of aneurysm patients have dysregulated Notch/BMP/WNT pathways compared to donor cells. Activity of Wnt pathway was significantly elevated in endothelial cells of the patients. Cells from patients had attenuated activation of DLL4, SNAIL1, DKK1 and BMP2 in response to shear stress. In conclusion endothelial cells of the patients with thoracic aortic aneurysm have dysregulated Notch, BMP and WNT/ß-catenin related signaling. Shear stress-response and cross-talk between Notch and Wnt pathways that normally ensures aortic integrity and resistance of endothelial cells to stress is impaired in aneurysmal patients.

10.
Curr Vasc Pharmacol ; 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30156160

RESUMO

Epidemiological evidence supports reduced prevalence of thoracic aortic aneurysm (TAA) in diabetes. The mechanisms underlying this negative association are unknown. Some studies support that hyperglycemia has effects on the extracellular matrix, resulting in collagen cross-links and altered proteolytic activity, which ultimately counteracts aneurysm formation. However, recent experimental research indicates that incretin-based anti-diabetic therapy and glucagon-like peptide-1 (GLP-1) may ameliorate formation of TAA. GLP-1 is a peptide hormone, released from intestinal L-cells in response to hormonal, neural and nutrient stimuli. In addition to potentiation of meal-stimulated insulin secretion, GLP-1 signaling exerts numerous pleiotropic effects on various tissues, including protective effects on the myocardium and vascular endothelium. Recent studies also report protective effects of GLP-1 based therapy on the formation of aneurysms in animal models and direct effects of GLP-1 signaling on the molecular mechanisms suggested to govern TAA formation, including inflammation, proteolytic activity and collagen composition. In this mini-review, we present the available evidence for effects of GLP-1 on experimental aneurysm development and discuss the potential role for GLP-1 in aneurysm formation based on available data from pre-clinical and clinical studies.

11.
J Thorac Dis ; 10(6): 3372-3380, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069332

RESUMO

Background: This study aimed to describe overall survival following pulmonary metastasectomy for colorectal cancer (CRC) in Sweden, and to assess the discrimination of a recently proposed risk prediction model. Methods: Individual-level data of 756 patients who underwent resection of pulmonary metastases from CRC between 2009 and 2015 were obtained from ThoR, a Swedish national quality register for thoracic surgery. We classified patients into three risk categories according to the number of preoperative risk factors [age, disease-free interval (DFI), presence of extrathoracic lesions, number of pulmonary metastases] established in a prior study. We estimated the hazard ratios (HRs) and 95% confidence interval (CI) by Cox regression and the restricted mean survival time difference as group contrast measures. Results: During a median follow-up time of 2.9 years, 35% (268/756) patients died. At 5 years, overall survival was 56% (95% CI: 51-60%). In a Cox regression model with risk category as the only independent variable, the HR for all-cause mortality was 1.94 (95% CI: 1.38-2.72, P<0.001) and 4.35 (95% CI: 2.49-7.62, P<0.001) in the moderate- (n=558) and high-risk categories (n=32), respectively, versus the low-risk category (n=166). At 5 years, the differences in restricted mean survival time were 6 months (P<0.001) and 1.5 years (P<0.001) in the moderate- and high-risk categories, respectively, versus the low-risk category. Conclusions: Five-year survival after surgery for pulmonary metastases from CRC in Sweden was similar or higher compared with contemporary reports. A prognostic model, initially developed in Japanese patients, had excellent discrimination in an external validation cohort of Swedish patients.

12.
J Thorac Dis ; 10(6): 3499-3506, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069346

RESUMO

Background: The aim of this nationwide observational cohort study was to investigate the early postoperative complications and long-term survival following video-assisted thoracoscopic surgery (VATS) lobectomy compared to open thoracotomy lobectomy for early stage non-small cell lung cancer (NSCLC). Methods: We used the Swedish national quality register for general thoracic surgery and included all patients who underwent lobectomy for NSCLC during 2012-2015. We compared postoperative complications and long-term survival in patients who underwent VATS lobectomy at our institution to patients who underwent open lobectomy at the other seven hospitals in Sweden. We used inverse probability of treatment weighting to limit differences in baseline characteristics between the groups and used standardized mean differences to assess balance after weighting. Results: We included 1,601 patients who underwent open (n=1,316) or VATS (n=285) lobectomy for NSCLC. The mean age was 67.7 years in both groups and comorbidities were well balanced, but the open thoracotomy group had a higher proportion of patients with more advanced cancer stage. After weighting, all baseline characteristics were well balanced. Most patients (84%) did not have postoperative complications; 83% vs. 86% in the open and VATS group, respectively (P=0.41). The 30- and 90-day mortality was 0.7% vs. 0.3% (P=0.38) and 1.7% vs. 0.3% (P=0.09) in the open thoracotomy and VATS group, respectively. There were significantly more transfusions (5.0% vs. 1.4%, P=0.008) and pneumonia (5.5% vs. 0.6%, P=0.002) in the in the open thoracotomy and VATS group, respectively. The overall survival at 1 and 5 years was 92% vs. 97% and 63% vs. 78% in the open thoracotomy and VATS group, respectively; HR (95% CI): 0.47 (0.33-0.68). Conclusions: We found less postoperative complications and better long-term survival following VATS lobectomy compared to open thoracotomy lobectomy for NSCLC. The implementation of a VATS lobectomy program did not compromise patient safety or the oncological efficacy.

13.
Blood ; 132(17): 1842-1850, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30042098

RESUMO

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29772584

RESUMO

BACKGROUND: Bovine and porcine bioprostheses are commonly used for surgical aortic valve replacement. It is unknown if the long-term survival differs between the two valve types.We performed a systematic review and meta-analysis to compare survival in patients who underwent aortic valve replacement and received a bovine or a porcine prosthesis. METHODS: We performed a systematic search of Medline, Embase, Web of Science, and the Cochrane Library. Cohort studies that compared survival between patients who underwent aortic valve replacement and received either a bovine or a porcine bioprosthesis and that reported overall long-term survival with hazard ratio (HR) and 95% confidence interval (CI) were included. Two authors independently reviewed articles considered for inclusion, extracted the information from each study, and performed the quality assessment. We performed a meta-analysis using a random effects model to calculate the pooled HR (95% CI) for all-cause mortality. We did sensitivity analyses to assess the robustness of our findings. RESULTS: Seven studies published between 2010 and 2015 were included, and the combined study population was 49,190 patients. Of these, 32,235 (66%) received a bovine, and 16,955 (34%) received a porcine bioprosthesis. There was no significant difference in all-cause mortality between patients who received a bovine compared with a porcine bioprosthesis (pooled HR 1.00, 95% CI: 0.92-1.09). Heterogeneity between studies was moderate (55.8%, p = 0.04). CONCLUSIONS: This systematic review and meta-analysis suggest no difference in survival between patients who received a bovine versus a porcine bioprosthesis after aortic valve replacement. Our study provides valuable evidence for the continuing use of both bovine and porcine bioprosthetic valves for surgical aortic valve replacement.

15.
Nat Commun ; 9(1): 987, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29511194

RESUMO

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.

16.
Sci Rep ; 8(1): 2777, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426841

RESUMO

Disturbed flow has been suggested to contribute to aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, flow has emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with in vitro studies of flow-sensitive methylation to identify biological processes associated with BAV-aortopathy and the potential contribution of flow. Biopsies from non-dilated and dilated ascending aortas were collected from BAV (n = 21) and tricuspid aortic valve (TAV) patients (n = 23). DNA methylation and gene expression was measured in aortic intima-media tissue samples, and in EA.hy926 and primary aortic endothelial cells (ECs) isolated from BAV and TAV exposed to oscillatory (±12 dynes/cm2) or laminar (12 dynes/cm2) flow. We show methylation changes related to epithelial-mesenchymal-transition (EMT) in the non-dilated BAV aorta, associated with oscillatory flow related to endocytosis. The results indicate that the flow-response in BAV ECs involves hypomethylation and increased expression of WNT/ß-catenin genes, as opposed to an angiogenic profile in TAV ECs. The EMT-signature was exasperated in dilated BAV aortas. Aberrant EMT in BAV aortic walls could contribute to increased aneurysm susceptibility, and may be due to disturbed flow-exposure. Perturbations during the spatiotemporally related embryonic development of ascending aorta and semilunar valves can however not be excluded.

17.
Clin Physiol Funct Imaging ; 38(5): 895-902, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29345099

RESUMO

BACKGROUND AND AIMS: Intima-media thickness is a marker for atherosclerosis but is also influenced by shear stress and flow. We evaluated the relation between intima-media thickness of the descending aorta (AoIMT) and the common carotid artery (CIMT) in patients with and without severe aortic valve disease (sAVD). METHODS: A total of 310 patients (233 with sAVD, 77 without) were examined with regard to AoIMT and CIMT using transesophageal echocardiography and carotid ultrasound, respectively, before valvular and/or aortic surgery. Digitally stored B-mode images were used for semiautomatic AoIMT and CIMT measurements. RESULTS: There were no significant differences in patients with or without sAVD with regard to AoIMT (1·35 ± 0·31 vs. 1·35 ± 0·33 mm) or CIMT (0·80 ± 0·15 vs. 0·78 ± 0·16 mm). The correlations between AoIMT and CIMT were r = 0·29 in patients with and r = 0·51 in patients without sAVD, and the difference between these correlations was significant (P<0·05). In multivariate regression, age was the main determinant for AoIMT and CIMT in both groups, further in sAVD, the aortic mean pressure gradient (Pmean ) was a determinant of AoIMT, but not of CIMT. CONCLUSIONS: The correlation between CIMT and AoIMT is weaker in patients with sAVD compared to those without sAVD. Pmean is also a significant predictor of AoIMT, but not of CIMT. This implies that, in addition to the atherosclerotic process, turbulent aortic flow or altered blood flow helicity created by large stroke volumes and diastolic flow reversal or high-velocity jets, affect the intima-media of the descending aorta and common carotid artery differently.


Assuntos
Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Ecocardiografia Transesofagiana , Doenças das Valvas Cardíacas/diagnóstico por imagem , Idoso , Aorta Torácica/fisiopatologia , Doenças da Aorta/fisiopatologia , Valva Aórtica/fisiopatologia , Aterosclerose/fisiopatologia , Velocidade do Fluxo Sanguíneo , Doenças das Artérias Carótidas/fisiopatologia , Artéria Carótida Primitiva/fisiopatologia , Estudos de Casos e Controles , Feminino , Doenças das Valvas Cardíacas/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Índice de Gravidade de Doença
19.
Interact Cardiovasc Thorac Surg ; 26(5): 790-797, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325064

RESUMO

OBJECTIVES: Right ventricular (RV) function is impaired after cardiac surgery, possibly because of the opening of the pericardium. In minimally invasive aortic valve replacement, the pericardium is only partially incised. METHODS: A randomized trial compared RV function after ministernotomy versus full sternotomy in 40 adults undergoing aortic valve replacement at the Karolinska University Hospital. Primary outcomes were tricuspid annular plane systolic excursion, RV pulsed-wave tissue Doppler velocity, RV fractional area change and basal and mid-RV transversal diameters on postoperative Days 4 and 40. RESULTS: On postoperative Day 4, the tricuspid annular plane systolic excursion had decreased in both groups [ministernotomy: median (Q1-Q3) 25 (21-28) vs 16 (11-18), P < 0.001; sternotomy: 22.5 (22-22.5) vs 8 (7-12) mm, P < 0.001] but was higher in the ministernotomy group (P < 0.001). Pulsed-wave tissue Doppler RV velocity decreased significantly in patients who underwent sternotomy [10.5 (10-12) vs 6.5 (5-8) cm/s, P < 0.001] but did not decrease significantly in patients who underwent ministernotomy [11.5 (11-12) vs 10 (9-11) cm/s, P = 0.054]. Fractional area change was equally decreased in both groups [ministernotomy: 46 (39-51) vs 38 (34-44)%, P < 0.001; sternotomy: 45 (40-49) vs 37 (25-39.5)%, P = 0.003]. RV dimensions did not change on postoperative Day 4 in both groups. The differences between the 2 groups were similar 40 days postoperatively. CONCLUSIONS: RV long-axis function was reduced after both ministernotomy and full sternotomy aortic valve replacement, but the reduction was more pronounced in the full sternotomy group. Global RV function was equally impaired in both groups postoperatively. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT01972555.

20.
Eur J Cardiothorac Surg ; 53(1): 276-281, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28977415

RESUMO

OBJECTIVES: Acute Type A aortic dissection remains a life-threatening disease, but there are indications that its surgical mortality is decreasing. The aim of this report was to study how surgical mortality has changed and what influences those changes. METHODS: Nordic Consortium for Acute Type A Aortic Dissection is a retrospective database comprising 1159 patients (mean age 61.6 ± 12.2 years, 68% male) treated for acute Type A aortic dissection at 8 centres in Denmark, Finland, Iceland and Sweden from 2005 to 2014. Data gathered included demographics, symptoms, type of procedure, complications and 30-day mortality. RESULTS: The annual number of operations increased significantly from 85 in 2005 to 150 in 2014 (P < 0.001). Chest pain was present in 85% of patients, 24% were hypotensive on presentation and 28% had malperfusion syndrome. Open distal anastomosis technique under hypothermic circulatory arrest was used in 85% of cases and its use increased significantly throughout the study. The 30-day mortality decreased from 24% in 2005 to 13% in 2014 (P = 0.003). Independent predictors for 30-day mortality were preoperative cardiac arrest, malperfusion syndrome, Penn Class C, Penn Class B and C and cardiopulmonary bypass time, whereas later calendar year and higher hospital operative volumes predicted improved survival. CONCLUSIONS: Surgical mortality for acute Type A aortic dissection remains high but has decreased significantly over the last decade. This correlated with later year of operation and increased the number of operations performed per year, indicating that cumulative surgical experience contributes significantly to improved surgical outcomes.


Assuntos
Aneurisma Dissecante/cirurgia , Aorta/cirurgia , Aneurisma Aórtico/cirurgia , Mortalidade Hospitalar/tendências , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Dissecante/mortalidade , Aneurisma Aórtico/mortalidade , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Países Escandinavos e Nórdicos/epidemiologia
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