I-κB kinase-ε knockout protects against angiotensin II induced aortic valve thickening in apolipoprotein E deficient mice.

Aortic stenosis (AS) is considered to be an actively regulated progress that involves similar pathophysiological processes as atherosclerosis. I-κB kinase-ε (IKKε) is a proinflammatory molecule involved in atherosclerosis. The objective of the present study was to define the role of IKKε in pathological valvular remodeling. Aortic valves (AVs) from 52 patients undergoing AV replacement (AS) and 13 patients undergoing heart transplant (Control) were analyzed. ApoE-/- mice (AK, n = 20) and ApoE-/-IKKε-/- mice (DK, n = 20) were generated and infused with saline or Ang II for 4 weeks. We found an upregulation of IKKε in human stenotic aortic valves compared to that in control AVs. Our results demonstrated that AK mice receiving AngII exhibited more advanced valvular remodeling and markedly increased IKKε expression. Conversely, loss of IKKε reduced adverse aortic valve thickening in response to Ang II, as measured by histological analyses. Furthermore, according to immunofluorescence analysis, Ang II resulted in obvious increases in the expression of α-SMA, TGF-ß and NF-κB pathway components in the AK group, especially in the thickened area, while these increases were blocked in the DK group. Moreover, IKKε was co-expressed with α-SMA in valvular interstitial cells in ApoE-/- mice after an AngII infusion. These data provide evidence that IKKε plays a key role in the development of valvular remodeling and that it may be a novel target for the treatment of AS.

Risk factors for early death in primary malignant cardiac tumors: An analysis of over 40 years and 500 patients.

OBJECTIVES: To investigate risk factors contributing to early death in patients diagnosed with primary malignant cardiac tumors (PMCTs) and derive better understanding of these poorly characterized individuals. METHOD: Data from the Surveillance, Epidemiology and End-Results (SEER) registries on 564 patients diagnosed with PMCTs between 1973 and 2014 were analyzed. Early death was defined as survival of ≤3 months from the time of diagnosis. Two-tailed χ2 or fisher's exact test were used for association between categorical variables and occurrence of early death. Logistic regression analysis was used to assess independent risk factors of early death. Time trends in early death rates of PMCTs were described using scatter plot. RESULTS: Of the 564 patients with PMCTs, early death was identified in 214 individuals (37.9%). Patients with unspecified soft tissue sarcomas and blood vessel tumors had the highest risk of early death. Age > 80 years and non-consent for surgery were strong predictors of early death in all PMCT subtypes. In sarcomas, disadvantaged income was associated with an increase in early mortality, while black race was associated with a reduction in early mortality. In mesotheliomas and others, male sex was a risk factor for early mortality, while Hispanic ethnicity was associated with a reduction in early mortality. Percentages of early death slightly decreased over the past 40 years. CONCLUSIONS: Predictors of early death are primarily related to age older than 80 years, no surgery and specific histopathology types but also include disadvantaged socioeconomic status and male sex. Initiatives to identify those at risk and develop preventive interventions should be prioritized.

The midterm results of coronary endarterectomy in patients with diffuse coronary artery disease.

BACKGROUND: Diffuse coronary artery disease is a challenge for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Coronary artery endarterectomy (CE) coupled with CABG is an alternative method to achieve complete revascularization. The mid- and long-term results of CE are largely questionable. The aim is to evaluate the early and mid-term graft patency of concomitant coronary artery endarterectomy and CABG. METHODS: A total of 304 patients who had undergone concomitant CE and CABG for diffuse coronary artery disease were identified from our database. A total of 238 patients (1) with complete operative records, (2) with good graft flow during surgery, (3) who were discharged, (4) with a one-year/ three-year follow-up were included in our study. The follow-up information was obtained directly from our out-patient department and by telephone contact. The categorical and continuous values were analyzed by Chi Square test and student's test respectively. RESULTS: CE was performed on 238 patients who represented a total of 269 target coronary vessels. The mean age of the patients was 67.8 ± 6.8 years old; male to female patient ratio was 170:68. The mean intensive care unit stay was 1.7 ± 8 days, and mean post-operative length of hospital stay was 11 ± 3 days. The average follow up time was 41.8 ± 21.4 months. At follow-up, the overall graft patency was 78.4% at one year and 69.8% at three years. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate (87.4% vs 73.1% at one-year and 78.2% vs 64.8% at three years). There was no significant difference in graft patency rates between the on-pump CE + CABG vs off-pump CE + CABG groups at one year (80.0% vs 76.9%) and at three years (92.3% vs 91.7%). At the one-year follow up, 92.3% of grafts showed grade A patency in the on-pump group versus 91.7% in the off-pump group; 7.7% of grafts showed grade B patency in the on-pump group versus 8.3% in the off-pump group. At the three-year follow up, 80.6% of grafts showed grade A patency in the on-pump group versus 77.4% in the off-pump group; 19.4% of grafts showed grade B patency in the on-pump group versus 22.6% in the off -pump group. The Predictors of better graft patency are use of LIMA graft, CE on LAD, and intra-operative graft flow meter and PI. CONCLUSIONS: In patients with diffuse coronary disease, CE is a safe and feasible technique for a select group of patients with excellent mid-term survival rates and graft patency rates. CE produces better overall results when performed on the LAD, and grafted over with the LIMA. Similar outcomes are obtained with both on-pump and off-pump surgery. For a select group of patients, coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and complete coronary revascularization.

Association between apolipoprotein E genotype and warfarin response during initial anticoagulation.

Apolipoprotein E (APOE) genotypes are associated with warfarin dose requirements in various populations. Whether APOE genotypes mediate the warfarin response is unknown. The aim of this study was to evaluate the genetic contributions of different APOE genotypes to the early phase of anticoagulation in Han Chinese patients. We conducted a retrospective cohort study and assessed APOE genotypes, clinical characteristics, international normalized ratio (INR) responses, warfarin dose requirements and bleeding events in 429 Han Chinese patients. The study outcomes were the time to the first INR within the therapeutic range, the time to the first INR of more than 4, the INR response over time, and the warfarin dose requirement. Compared with patients with the ε3/ε3 genotype, patients with at least one ε4 allele had significantly longer times to the first INR of more than 4 during both the initial 20 days (P = 0.001, HR 2.9; 95%CI, 1.54-5.45) and the entire follow-up period (P < 0.001, HR 3.26; 95%CI,1.94-5.47), but this allele was not a significant predictor of the time to the first INR within the therapeutic range. No association was observed between the ε2 allele and INR response, and both the ε4 allele and the ε2 allele did not significantly affect the required warfarin dose during the follow-up. These observations suggest that genetic variants of APOE are associated with an increased risk of overanticoagulation among the Han Chinese population. However, these variants may not be useful in predicting warfarin maintenance dose requirements.