Severe aortic stenosis: diagnosis, treatment and prognosis

Degenerative aortic stenosis is the most common valvular heart disease in developed countries. The prevalence of severe aortic stenosis increases with age from 1% in people below 65 years of age to nearly 6% in people over the age of 85. Since the population li

Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials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 We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.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 Investigators were contacted for unpublished information about venous thromboembolic events during follow-up.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

Left Ventricular Endocardial Pacing Improves Resynchronization Therapy in Canine Left Bundle-Branch Hearts

Background— We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. Methods and Results— In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79�31 versus 32�24 ms, P <0.05) and LVdP/dtmax (92�29 versus 63�39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40�21 ms) transmural dispersion of repolarization. Conclusions— Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy

Incidence, Predictors, and Significance of Abnormal Cardiac Enzyme Rise in Patients Treated With Bypass Surgery in the Arterial Revascularization Therapies Study (ARTS)

BACKGROUND: Although it has been suggested that elevation of CK-MB after percutaneous coronary intervention is associated with adverse clinical outcomes, limited data are available in the setting of coronary bypass grafting. The aim of the present study was to determine the incidence, predictors, and prognostic significance of CK-MB elevation following multivessel coronary bypass grafting (CABG). METHODS AND RESULTS: The population comprises 496 patients with multivessel coronary disease assigned to CABG in the Arterial Revascularization Therapies Study (ARTS). CK-MB was prospectively measured at 6, 12, and 18 hours after the procedure. Thirty-day and 1-year clinical follow-up were performed. Abnormal CK-MB elevation occurred in 61.9% of the patients. Patients with increased cardiac-enzyme levels after CABG were at increased risk of both death and repeat myocardial infarction within the first 30 days (P=0.001). CK-MB elevation was also independently related to late adverse outcome (P=0.009, OR=0.64). CONCLUSIONS: Increased concentrations of CK-MB, which are often dismissed as inconsequential in the setting of multivessel CABG, appear to occur very frequently and are associated with a significant increase in both repeat myocardial infarction and death beyond the immediate perioperative period

Chronic ventricular pacing in children: toward prevention of pacing-induced heart disease

In children with congenital or acquired complete atrioventricular (AV) block, ventricular pacing is indicated to increase heart rate. Ventricular pacing is highly beneficial in these patients, but an important side effect is that it induces abnormal electrical activation patterns. Traditionally, ventricular pacemaker leads are positioned at the right ventricle (RV). The dyssynchronous pattern of ventricular activation due to RV pacing is associated with an acute and chronic impairment of left ventricular (LV) function, structural remodeling of the LV, and increased risk of heart failure. Since the degree of pacing-induced dyssynchrony varies between the different pacing sites, ‘optimal-site pacing’ should aim at the prevention of mechanical dyssynchrony. Especially in children, generally paced from a very early age and having a perspective of life-long pacing, the preservation of cardiac function during chronic ventricular pacing should take high priority. In the perspective of the (patho)physiology of ventricular pacing and the importance of the sequence of activation, this paper provides an overview of the current knowledge regarding possible alternative sites for chronic ventricular pacing. Furthermore, clinical implications and practical concerns of the various pacing sites are discussed. The review concludes with recommendations for optimal-site pacing in children

Usefulness of microsimulation to translate valve performance into patient outcome: Patient prognosis after aortic valve replacement with the Carpentier–Edwards supra-annular valve

ObjectiveNumerous reports have been published documenting the results of aortic valve replacement. It is often not easy to translate these outcomes involving the condition of the valve into the actual consequences for the patient. We previously developed an alternative method to study outcome after aortic valve replacement that allows direct estimation of patient outcome after aortic valve replacement: microsimulation modeling. The goal of this article is to provide insight into microsimulation methodology and to give an overview of the advantages and disadvantages of simulation methods (in particular microsimulation) in comparison with standard methods of outcome analysis.MethodsBy using a primary dataset containing 1847 patients and 14,429 patient-years, advantages and disadvantages of standard methods of outcome analysis are discussed, and the potential role of microsimulation is illustrated by means of a step-by-step explanation of building, testing, and using such a model.ResultsTotal life expectancy, event-free life expectancy, and reoperation-free life expectancy for a 65-year-old male patient were 10.6 years, 9.2 years, and 9.8 years, respectively. Lifetime risk of reoperation due to structural valve deterioration was 13.3%.ConclusionsMicrosimulation is capable of providing accurate estimates of age-related life expectancy and lifetime risk of reoperation for patients who underwent aortic valve replacement with the Carpentier–Edwards supra-annular valve. It provides a useful tool to facilitate and optimize the choice for a specific heart valve prosthesis in a particular patient

When is an optimization not an optimization? Evaluation of clinical implications of information content (signal-to-noise ratio) in optimization of cardiac resynchronization therapy, and how to measure and maximize it

Impact of variability in the measured parameter is rarely considered in designing clinical protocols for optimization of atrioventricular (AV) or interventricular (VV) delay of cardiac resynchronization therapy (CRT). In this article, we approach this question quantitatively using mathematical simulation in which the true optimum is known and examine practical implications using some real measurements. We calculated the performance of any optimization process that selects the pacing setting which maximizes an underlying signal, such as flow or pressure, in the presence of overlying random variability (noise). If signal and noise are of equal size, for a 5-choice optimization (60, 100, 140, 180, 220 ms), replicate AV delay optima are rarely identical but rather scattered with a standard deviation of 45 ms. This scatter was overwhelmingly determined (ρ = −0.975, P < 0.001) by Information Content, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\frac{\text{Signal}}{{{\text{Signal}} + {\text{Noise}}}}}$$\end{document}, an expression of signal-to-noise ratio. Averaging multiple replicates improves information content. In real clinical data, at resting, heart rate information content is often only 0.2–0.3; elevated pacing rates can raise information content above 0.5. Low information content (e.g. <0.5) causes gross overestimation of optimization-induced increment in VTI, high false-positive appearance of change in optimum between visits and very wide confidence intervals of individual patient optimum. AV and VV optimization by selecting the setting showing maximum cardiac function can only be accurate if information content is high. Simple steps to reduce noise such as averaging multiple replicates, or to increase signal such as increasing heart rate, can improve information content, and therefore viability, of any optimization process

Animal Models of Dyssynchrony

Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT