A study of prevalence of peripheral arterial disease in type 2 diabetes mellitus using ankle-brachial index and its correlation with coronary artery disease and its risk factors

Background: Peripheral arterial disease (PAD) is one of the macrovascular complications of type 2 diabetes mellitus (T2DM). There is significant difference in the reported prevalence of PAD and its associated risk factors between Indian and Western studies. The purpose of this study was to examine the PAD complicating T2DM, in particular the influence of PAD on the risk of CAD.Methods: Randomly selected 100 T2DM patients presented to Guru Nanak Dev hospital were included. In addition to a detailed history and physical examination, anthropometric parameters like body mass index was measured. CAD in patients was diagnosed by a history of angina, ECG changes, any past history of CAD or any treatment taken for CAD. Ankle brachial index (ABI) was measured. Data was collected systematically and analyzed according to the standard statistical methods.Results: The prevalence of PAD was 15%. CAD was present in 31%. PAD was found to be significantly correlated with age, duration of diabetes, smoking, systolic blood pressure, diastolic blood pressure, prevalence of BMI >25 kg/m2, HbA1c and serum HDL ≤40 mg%. Old age, high HbA1c level, and dyslipidaemia were found to be significant independent predictors of CAD.Conclusions: Using ABI authors found evidence of PAD in 15% patients of T2DM. The prevalence of CAD was higher in patients with PAD. So, there is definite and strong correlation between PAD and CAD. Thus, the early diagnosis of PAD should alert the clinician to a high probability of underlying CAD

Novel insights in pathophysiology of postoperative atrial fibrillation

OBJECTIVES: Atrial extrasystoles are usually benign; however, they can also trigger atrial fibrillation. It is most likely that if atrial extrasystoles provoke a larger amount of conduction disorders and a greater degree of endo-epicardial asynchrony, the risk of postoperative atrial fibrillation increases. To test this hypothesis, we investigated the effect of programmed atrial extrasystoles on endo-epicardial conduction and postoperative atrial fibrillation. METHODS: Twelve patients (58% male, age 68 ± 7 years) underwent simultaneous endo-epicardial mapping (256 electrodes) of the right atrium during sinus rhythm and programmed atrial extrasystoles provoked from the right atrial free wall. Areas of conduction block were defined as conduction delays of ≥12 milliseconds and endo-epicardial asynchrony as activation time differences of exact opposite electrodes of ≥15 milliseconds. RESULTS: Endo-epicardial mapping data of all programmed atrial extrasystoles were analyzed and compared with sinus rhythm (median preceding cycle length = 531 milliseconds [345-787] and median sinus rhythm cycle length = 843 milliseconds [701-992]). All programmed atrial extrasystoles were aberrant (severe, moderate, and mildly aberrant, respectively, n = 6, 3, and 3) and had a mean prematurity index of 50.1 ± 11.9%. The amount of endo-epicardial asynchrony (1% [1-2] vs 6.7 [2.7-16.9], P = .006) and conduction block (1.4% [0.6-2.6] vs 8.5% [4.2-10.4], P = .005) both increased during programmed atrial extrasystoles. Interestingly, conduction block during programmed atrial extrasystoles was more severe in patients (n = 4, 33.3%) who developed postoperative atrial fibrillation (5.1% [2.9-8.8] vs 11.3% [10.1-12.1], P = .004). CONCLUSIONS: Atrial conduction disorders and endo-epicardial asynchrony, which play an important role in arrhythmogenesis, are enhanced during programmed atrial extrasystoles compared with sinus rhythm. The findings of this pilot study provide a possible explanation for enhanced vulnerability for postoperative atrial extrasystoles to induce postoperative atrial fibrillation in patients after cardiac surgery

Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase

BACKGROUND: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. RESULTS: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. CONCLUSIONS: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function

Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression.

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair

Characterization of pre-existing arrhythmogenic substrate associated with de novo early and late postoperative atrial fibrillation

Background: PoAF is the most common complication after cardiac surgery and may occur in patients with pre-existing arrhythmogenic substrate. Characterization of this substrate could aid in identifying patients at risk for PoAF. We therefore compared intra-atrial conduction parameters and electrogram morphology between patients without and with early- (≤5 days after surgery) and late- (up to 5 years) postoperative atrial fibrillation (PoAF). Methods and results: Epicardial mapping of the right and left atrium and Bachmann's Bundle (BB) was performed during sinus rhythm (SR) in 263 patients (207male, 67 ± 11 years). Unipolar potentials were classified as single, short or long double and fractionated potentials. Unipolar voltage, fractionation delay (time difference between the first and last deflection), conduction velocity (CV) and conduction block (CB) prevalence were measured. Comparing patients without (N = 166) and with PoAF (N = 97), PoAF was associated with lower CV and more CB at BB. Unipolar voltages were lower and more low-voltage areas were found at the left and right atrium and BB in PoAF patients. These differences were more pronounced in patients with late-PoAF (6%), which could even occur up to 5 years after surgery. Although several electrophysiological parameters were related to PoAF, age was the only independent predictor. Conclusions: Patients with de novo PoAF have more extensive arrhythmogenic substrate prior to cardiac surgery compared to those who remained in SR, which is even more pronounced in late-PoAF patients. Future studies should evaluate whether intra-operative electrophysiological examination enables identification of patients at risk for developing PoAF and hence (preventive) therapy.</p

Ultrasound- Versus Fluoroscopy-Guided Strategy for Transfemoral Transcatheter Aortic Valve Replacement Access: A Systematic Review and Meta-Analysis

Background:Access site vascular and bleeding complications remain problematic for patients undergoing transcatheter aortic valve replacement (TAVR). Ultrasound-guided transfemoral access approach has been suggested as a technique to reduce access site complications, but there is wide variation in adoption in TAVR. We performed a systematic review and meta-analysis to compare access site vascular and bleeding complications according to the Valve Academic Research Consortium-2 classification following the use of either ultrasound- or conventional fluoroscopy-guided transfemoral TAVR access.Methods:Medline, Embase, Web of Science, and The Cochrane Library were searched to November 2020 for studies comparing ultrasound- and fluoroscopy-guided access for transfemoral TAVR. A priori defined primary outcomes were extracted: (1) major, (2) minor, and (3) major and minor (total) access site vascular complications and (4) life-threatening/major, (5) minor, and (6) life-threatening, major, and minor (total) access site bleeding complications.Results:Eight observational studies (n=3875) were included, with a mean participant age of 82.8 years, STS score 5.81, and peripheral vascular disease in 23.5%. An ultrasound-guided approach was significantly associated with a reduced risk of total (Mantel-Haenszel odds ratio [MH-OR], 0.50 [95% CI, 0.35–0.73]), major (MH-OR, 0.51 [95% CI, 0.35–0.74]), and minor (MH-OR, 0.59 [95% CI, 0.38–0.91]) access site vascular complications. Ultrasound guidance was also significantly associated with total access site bleeding complications (MH-OR, 0.59 [95% CI, 0.39–0.90]). The association remained significant in sensitivity analyses of maximally adjusted minor and total vascular access site complications (MH-OR, 0.51 [95% CI, 0.29–0.90]; MH-OR, 0.44 [95% CI, 0.20–0.99], respectively).Conclusions:In the absence of randomized studies, our data suggests a potential benefit for ultrasound guidance to obtain percutaneous femoral access in TAVR