Sex differences in coronary artery disease presentation and outcomes have been described. The aim of this study was to compare sex disparities in chronic total occlusion (CTO) management and ...long-term outcomes.
All consecutive patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortality were assessed during a median follow-up of 4.03 years (IQR 2.6–4.8).
A total of 1248 patients (67.3 ± 10.9 years; 16% female) were identified. Women were older, had a higher prevalence of type 2 DM and a lower ventricle ejection fraction compared to men (p < .05). Although women had major proportion of positive result for severe ischemia-viability test (86% vs. 74%; p = .01), they were more often treated with MT alone compared to male (57% vs 51%; p = .02). During follow-up, 386 patients (31%) died. Women presented a higher rate of all-cause and cardiac mortality, and hospitalizations for heart failure independently of treatment strategy, compared to men (p < .001). In multivariable analysis female sex was associated with higher cardiac mortality HR 1.67, 95% CI 1.10–2.57; p < .001. Among women, the independent predictors for all-cause and cardiac mortalities were age, MT of the CTO and ACEF (age, creatinin and ejection fraction) score.
A significant sex gap regarding CTO treatment was observed. Female sex was an independent predictor for cardiac mortality at long-term follow-up. More data are needed to support these findings.
•Despite recent advancements in CTO treatments, a significant sex gap remains.•Women were more often treated with MT alone, but men were more likely to undergo invasive strategies.•Female sex in CTO patients was associated with higher cardiac mortality.
Activin receptor-like kinase-1 (ALK1) is an endothelial transforming growth factor β receptor involved in angiogenesis. ALK1 expression is high in the embryo vasculature, becoming less detectable in ...the quiescent endothelium of adult stages. However, ALK1 expression becomes rapidly increased after angiogenic stimuli such as vascular injury.
To characterize the molecular mechanisms underlying the regulation of ALK1 on vascular injury.
Alk1 becomes strongly upregulated in endothelial (EC) and vascular smooth muscle cells of mouse femoral arteries after wire-induced endothelial denudation. In vitro denudation of monolayers of human umbilical vein ECs also leads to an increase in ALK1. Interestingly, a key factor in tissue remodeling, Krüppel-like factor 6 (KLF6) translocates to the cell nucleus during wound healing, concomitantly with an increase in the ALK1 gene transcriptional rate. KLF6 knock down in human umbilical vein ECs promotes ALK1 mRNA downregulation. Moreover, Klf6(+/-) mice have lower levels of Alk1 in their vasculature compared with their wild-type siblings. Chromatin immunoprecipitation assays show that KLF6 interacts with ALK1 promoter in ECs, and this interaction is enhanced during wound healing. We demonstrate that KLF6 is transactivating ALK1 gene, and this transactivation occurs by a synergistic cooperative mechanism with specificity protein 1. Finally, Alk1 levels in vascular smooth muscle cells are not directly upregulated in response to damage, but in response to soluble factors, such as interleukin 6, released from ECs after injury.
ALK1 is upregulated in ECs during vascular injury by a synergistic cooperative mechanism between KLF6 and specificity protein 1, and in vascular smooth muscle cells by an EC-vascular smooth muscle cell paracrine communication during vascular remodeling.
Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability to switch to a noncontractile, migratory, and proliferating phenotype. Although ...the participation of ion channels in this phenotypic modulation (PM) has been described previously, changes in their expression are poorly defined because of their large molecular diversity. We obtained a global portrait of ion channel expression in contractile versus proliferating mouse femoral artery VSMCs, and explored the functional contribution to the PM of the most relevant changes that we observed.
High-throughput real-time polymerase chain reaction of 87 ion channel genes was performed in 2 experimental paradigms: an in vivo model of endoluminal lesion and an in vitro model of cultured VSMCs obtained from explants. mRNA expression changes showed a good correlation between the 2 proliferative models, with only 2 genes, Kv1.3 and Kvbeta2, increasing their expression on proliferation. The functional characterization demonstrates that Kv1.3 currents increased in proliferating VSMC and that their selective blockade inhibits migration and proliferation.
These findings establish the involvement of Kv1.3 channels in the PM of VSMCs, providing a new therapeutical target for the treatment of intimal hyperplasia.
Abstract Decision making in acute chest pain remains challenging despite normal (<99th percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ...99th percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised of 682 patients (November 2010/September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/L). The main endpoint was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina or revascularization) at a 4-year median follow-up; secondary endpoint was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain), and 2 points (recurrent pain and prior ischemic heart disease).The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/L), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI risk (0.68, 0.77) or GRACE (0.50, 0.47) scores. Likewise, the negative predictive values of score= 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both a clinical score of 0 and ≤1 classified better patients at risk of MACE (p=0.0001, log rank test) than hs-cTnT<5 ng/L (p=0.06). In conclusion, clinical data can guide decision making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.
High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome.
A total of 1372 consecutive ...patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation).
There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02).
hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.
Abstract Background Mild therapeutic hypothermia (MTH) is associated with an increased risk of both thrombotic and bleeding events. Although little is known about the use of Glycoprotein IIb-IIIa ...inhibitors (GPi) in this setting, the early action and the intravenous administration of these agents in patients who cannot swallow might potentially translate into clinical benefits in patients with acute coronary syndromes (ACS). Aims To assess the incidence of bleeding/thrombotic events in patients with ACS under MTH after an Out-of-hospital cardiac arrest (OHCA) who received GPi or not. Methods and Results From January 2010 to September 2015, 110 patients were treated with MTH after an OHCA. Among them, 88 (80%) had an ACS and 71 patients (80.6%) underwent percutaneous coronary intervention (PCI). In 17 (24%) GPi were administered in the cath-lab. During hospitalization, 11.7% in the GPi and 9.25%in the non GPi group presented thrombotic events (stent thrombosis, deep vein thrombosis, pulmonary embolism) without significant differences between groups ( p = 0.762). The incidence of any bleeding (64.7% vs. 14.8%; p < 0.0001), and major bleeding (41.1% vs. 3.7; p < 0.0001) was significantly higher in patients receiving GPi. Finally, in-hospital mortality did not differ between groups (24% vs. 35, 2%; p = 0.385). Conclusions In this study, the use of GPi in patients with ACS undergoing PCI under MTH was associated with an increased bleeding risk without reduction of thrombotic events. According to these results, the use of GPi should be carefully considered in this setting.
ROLE OF KV1.3 CHANNELS IN INTIMAL HYPERPLASIA Novensa, Mercè Roquè. Laura; Cidad, Pilar; Batlle, Montserrat ...
Journal of the American College of Cardiology,
03/2012, Letnik:
59, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Background Vascular smooth muscle cells (VSMCs) are able to switch from a contractile to a proliferative phenotype, and this process is central to intimal hyperplasia formation.
We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + ...CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration.
The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, ...has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts.
We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls.
There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples.
These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.
The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a ...potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation.
This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively.
The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391).
A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.
PDF
