Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials

Background - It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings - We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. Conclusions - The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out

Exploring the cause of conduction delays in patients with repaired Tetralogy of Fallot

Aim Cardiac dyssynchrony in patients with repaired Tetralogy of Fallot (rToF) has been attributed to right bundle branch block (RBBB), fibrosis and/or the patches that are inserted during repair surgery. We aimed to investigate the basis of abnormal activation in rToF patients by mapping the electrical activation sequence during sinus rhythm (SR) and right ventricular (RV) pacing.Methods and Results A total of 17 patients were studied [13 with rToF, 2 with left bundle branch block (LBBB), and 2 without RBBB or LBBB (non-BBB)] during medically indicated cardiac surgery. During SR and RV pacing, measurements were performed using 112-electrode RV endocardial balloons (rToF only) and biventricular epicardial sock arrays (four of the rToF and all non-rToF patients). During SR, functional lines of block occurred in five rToF patients, while RV pacing caused functional blocks in four rToF patients. The line of block persisted during both SR and RV pacing in only 2 out of 13 rToF patients. Compared to SR, RV pacing increased dispersion of septal activation, but not dispersion of endocardial and epicardial activation of the RV free wall. During pacing, RV and left ventricular activation dispersion in rToF patients were comparable to that of the non-rToF patients.Conclusion The results of the present study indicate that the delayed activation in the right ventricle of rToF patients is predominantly due to block(s) in the Purkinje system and that conduction in RV tissue is fairly normal

Pressure-dependence of arterial stiffness: potential clinical implications

Background: Arterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age. Methods: Using a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80mmHg) pressure ranges. Results: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings. Conclusion: Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements

An audit of uncertainty in multi-scale cardiac electrophysiology models

Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical applications including guidance for clinical procedures and for drug safety assessment. As a consequence, there is an urgent need for a more detailed and quantitative understanding of the ways that uncertainty and variability influence model predictions. In this paper, we review the sources of uncertainty in these models at different spatial scales, discuss how uncertainties are communicated across scales, and begin to assess their relative importance. We conclude by highlighting important challenges that continue to face the cardiac modelling community, identifying open questions, and making recommendations for future studies. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’

Pressure-Corrected Carotid Stiffness and Young's Modulus: Evaluation in an Outpatient Clinic Setting

Background: Conventional measures for assessing arterial stiffness are inherently pressure dependent. Whereas statistical pressure adjustment is feasible in (larger) populations, it is unsuited for the evaluation of an individual patient. Moreover, statistical "correction"for blood pressure may actually correct for: (i) the acute dependence of arterial stiffness on blood pressure at the time of measurement; and/or (ii) the remodeling effect that blood pressure (hypertension) may have on arterial stiffness, but it cannot distinguish between these processes. METHODS: We derived - assuming a single-exponential pressure-diameter relationship - 3 theoretically pressure-independent carotid stiffness measures suited for individual patient evaluation: (i) stiffness index β0, (ii) pressure-corrected carotid pulse wave velocity (cPWVcorr), and (iii) pressure-corrected Young's modulus (Ecorr). Using linear regression analysis, we evaluated in a sample of the CATOD study cohort changes in mean arterial pressure (ΔMAP) and comparatively the changes in the novel (Δβ0, ΔcPWVcorr, and ΔEcorr) as well as conventional (ΔcPWV and ΔE) stiffness measures after a 2.9 ± 1.0-year follow-up. RESULTS: We found no association between ΔMAP and Δβ0, ΔcPWVcorr, or ΔEcorr. In contrast, we did find a significant association between ΔMAP and conventional measures ΔcPWV and ΔE. Additional adjustments for biomechanical confounders and traditional risk factors did neither materially change these associations nor the lack thereof. Conclusions: Our newly proposed pressure-independent carotid stiffness measures avoid the need for statistical correction. Hence, these measures (β0, cPWVcorr, and Ecorr) can be used in a clinical setting for (i) patient-specific risk assessment and (ii) investigation of potential remodeling effects of (changes in) blood pressure on intrinsic arterial stiffness

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age 50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age

Comparison of 2D and 3D calculation of left ventricular torsion as circumferential-longitudinal shear angle using cardiovascular magnetic resonance tagging

<p>Abstract</p> <p>Purpose</p> <p>To compare left ventricular (LV) torsion represented as the circumferential-longitudinal (CL) shear angle between 2D and 3D quantification, using cardiovascular magnetic resonance (CMR).</p> <p>Methods</p> <p>CMR tagging was performed in six healthy volunteers. From this, LV torsion was calculated using a 2D and a 3D method. The cross-correlation between both methods was evaluated and comparisons were made using Bland-Altman analysis.</p> <p>Results</p> <p>The cross-correlation between the curves was <it>r</it>²= 0.97 ± 0.02. No significant time-delay was observed between the curves. Bland-Altman analysis revealed a significant positive linear relationship between the difference and the average value of both analysis methods, with the 2D results showing larger values than the 3D. The difference between both methods can be explained by the definition of the 2D method.</p> <p>Conclusion</p> <p>LV torsion represented as CL shear quantified by the 2D and 3D analysis methods are strongly related. Therefore, it is suggested to use the faster 2D method for torsion calculation.</p