Lieven N. Kennes

Risk factors for mortality and failure of conservative treatment after aortic type B dissection.

BACKGROUND Despite medical treatment, one third of patients with uncomplicated type B aortic dissections experience severe late complications. The aim of this study was to identify patients at high risk of mortality during follow-up. METHODS A total of 183 patients with acute Stanford type B dissection were treated in one of the university hospitals (Aachen [Germany], Maastricht [The Netherlands], and Innsbruck [Austria]) between 1997 and 2010. Records indicated that 120 patients were treated conservatively. Of these patients, 16 were lost to follow-up. The maximum diameter, extent of the dissection, and patency of the side branches were determined from computed tomography angiography data. Survival and treatment failure were analyzed by univariate and multivariate Cox regression analysis. The univariate analysis investigated the influence of aortic diameter (≥41 vs <41 mm) on survival, and the multivariate analysis investigated the influence of aortic diameter, age, sex, and surgery on survival. RESULTS During the follow-up period, the initial treatment was converted to surgical treatment in 21 patients (20.2%). Sixteen of the 104 patients (15.4%) died after a mean of 845.5±805.9 days. The mean maximum aortic transversal diameter at admission was 41.2±8.7 mm. The multivariate analysis identified aortic diameter (P=.004; hazard ratio, 1.07) and age (P=.038; hazard ratio, 1.05) as risk factors that significantly reduce survival. CONCLUSIONS Our study revealed both early aortic dilatation and older age as risk factors for increased mortality after conservative treatment of type B dissection.

The impact of selection bias on test decisions in randomized clinical trials

Selection bias affects the evaluation of clinical trials, for example, by elevating type I error rate. We investigated the effect of selection bias on type I error rate considering permuted block randomization. We also considered stratified randomization in general and for the special case of multicenter clinical trials, where we incorporated preferences of the investigator in our approach. Finally, the effect of underrunning is modeled, that is, where the randomization list exceeds the actual number of patients taking part in the trial. For all situations, we illustrate and discuss the impact of selection bias on type I error rate.

Impact of Transcutaneous Aortic Valve Implantation on Myocardial Deformation

Aims: To define the impact of transcutaneous aortic valve implantation (TAVI) using the CoreValve prosthesis on myocardial deformation in a serial echocardiographic study with analysis of strain and strain rate. Methods: In 36 patients (83 ± 6 years; EuroScore: 26 ± 13%) with severe aortic stenosis scheduled for CoreValve implantation serial echocardiographic studies pre‐ and postintervention (within 1 month) were performed. Midparasternal short‐axis and three apical views were acquired. Using customized computer software which allows automatic frame‐by‐frame tracking of acoustic markers during the heart cycle circumferential, radial, and longitudinal strain (CS, RS, and LS) and strain rate (CSR, RSR, and LSR) were calculated for each segment in a 16 segment model of the left ventricle. Results: Longitudinal strain, systolic, and early diastolic longitudinal strain rate increased significantly within 1 month after TAVI (LS from –15.8 ± 3.6% to –17.6 ± 3.1%; P < 0.001; LSR(S) from –1.03 ± 0.21 s−1 to –1.21 ± 0.19 s−1; P < 0.001 and LSR (E) from –1.15 ± 0.42 s−1 to 1.51 ± 0.44 s−1; P < 0.001). Circumferential strain and strain rate values remained unchanged after CoreValve implantation. RS (29.1 ± 17.1 to 34.0 ± 15.8%; ns), RSR (S) (1.56 ± 0.69 to 1.91 ± 0.87 s−1; ns) and RSR(E) (–1.56 ± 0.78 to –1.81 ± 0.82 s−1; ns) increased only nonsignificantly after TAVI. Analysis of covariance showed only chronic kidney disease to have a relevant impact on early diastolic LSR (P = 0.01). Conclusions: Mainly longitudinal mechanics respond to unloading of the left ventricle after TAVI for severe aortic stenosis while radial and circumferential deformation is substantially unchanged. Pacemaker implantation or onset of left bundle brunch block after TAVI do not influence early myocardial deformation parameters. (Echocardiography 2011;28:397‐401)

The impact of selective visceral perfusion on intestinal macrohemodynamics and microhemodynamics in a porcine model of thoracic aortic cross-clamping.

INTRODUCTION Despite its presumed effectiveness and clinical use, the physiology of selective visceral perfusion combined with distal aortic perfusion during open thoracoabdominal aortic surgery has not been characterized. Thus, the aim of this study was to establish a translatable model of thoracic aortic-clamping to assess the effect of selective visceral perfusion with added distal aortic perfusion on local intestinal macrohemodynamics and microhemodynamics, intestinal histopathology, and markers of inflammation and intestinal damage. METHODS A thoracolaparotomy was performed in 15 pigs, and the aorta was exposed, including the origins of celiac trunk and superior mesenteric artery. The animals were divided into three cohorts: control (I), thoracic aortic cross-clamping (II), and thoracic aortic cross-clamping with selective visceral perfusion plus distal aortic perfusion using extracorporeal circulation (III). Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurements and fluorescent microspheres. Intestinal ischemia-reperfusion injury was determined by the analysis of perioperative intestinal fatty acid-binding protein (IFABP) and interleukin-8 (IL-8) levels and correlated with histopathologic changes. RESULTS Severe intestinal tissue injury and an inflammatory response were observed in cohort II compared with cohort III for IL-8 (38.2 vs 3.56 pg/mL; P = .04). The procedure in cohort III resulted in a flow and pressure-associated intestinal hypoperfusion compared with cohort I in the superior mesenteric artery (mean blood pressure, 24.1 ± 10.4 vs 67.2 ± 7.4 mm Hg; P < .0001; mean flow rates: 353.3 ± 133.8 vs 961.7 ± 310.8 mL/min; P < .0001). This was paralleled in cohort III vs cohort I by a significant mucosal injury (IFABP, 713 ± 307.1 vs 170 ± 115.4 pg/mL; P = .014) despite a profound recruitment of intestinal microcirculation (338% ± 206.7% vs 135% ± 123.7%; P = .05). CONCLUSIONS This study reports a novel large-animal model of thoracic aortic cross-clamping that allows the study of visceral perfusion strategies. However, we demonstrated with IL-8 and IFABP measurements that thoracoabdominal aortic aneurysm surgery with selective visceral perfusion and distal aortic perfusion is superior to the clamp-and-sew technique, even though small intestinal tissue damage cannot be completely avoided by selective visceral perfusion and distal aortic perfusion. In any case, this model seems to be a platform to evaluate and optimize measures for gut wall protection.

Cardiovascular remodeling during arteriovenous fistula maturation in a rodent uremia model

Purpose The aim of this study was to evaluate cardiovascular remodeling after arteriovenous fistula (AVF) surgery and to characterize the effect of chronic kidney disease (CKD) in a rodent femoral AVF model. Methods Sixteen rats (8 healthy; 8 CKD) underwent femoral AVF surgery; 4 animals served as controls. AVF and cardiac morphology as well as function were assessed during the fistula maturation process (until day 84 after surgery) using magnetic resonance imaging and histopathological analyses. Results Histopathological analysis revealed that a glomerular and interstitial nephropathy caused CKD. In healthy and CKD animals, AVF surgery resulted in progressive downstream vein dilation and a subsequent cardiac adaptation. This vein dilation during maturation was less in CKD rats during the early postoperative course (day 21: p=0.0475) and similar thereafter until day 84. The dilation was accompanied by an aggravation of neointimal hyperplasia (NIH) and calcification in AVFs of CKD rats. The chronic volume overload resulted in both groups in a significantly increased end-diastolic volume (healthy rats: p=0.0087; CKD rats: p=0.0333). Simultaneously, cardiac output increased 195% in healthy and 244% in uremic rats, which was caused by both a significantly increased stroke volume and heart rate. The left ventricular mass rose in AVF animals and was increased at the end of the study period, indicating a distinct cardiac hypertrophy. Conclusion Our rat model showed typical cardiovascular features of the AVF maturation process, which strongly resemble clinical findings in patients. Uremia caused inferior dilation in the early phase after surgery and an exacerbation of NIH. This model should help to identify the cellular and molecular mechanisms that contribute to AVF failure.

Inference for blocked randomization under a selection bias model

We provide an asymptotic test to analyze randomized clinical trials that may be subject to selection bias. For normally distributed responses, and under permuted block randomization, we derive a likelihood ratio test of the treatment effect under a selection bias model. A likelihood ratio test of the presence of selection bias arises from the same formulation. We prove that the test is asymptotically chi-square on one degree of freedom. These results correlate well with the likelihood ratio test of Ivanova et al. (2005, Statistics in Medicine 24, 1537-1546) for binary responses, for which they established by simulation that the asymptotic distribution is chi-square. Simulations also show that the test is robust to departures from normality and under another randomization procedure. We illustrate the test by reanalyzing a clinical trial on retinal detachment.

Outcome after mitral valve operations with depressed left ventricular function.

We retrospectively investigated 42 patients (27 men, 15 women; mean age, 67 years) with severe mitral valve incompetence and endstage cardiomyopathy (ejection fraction <30%) who were operated on between January 2002 and March 2009. Of these, 14 were in New York Heart Association class IV, and 27 were in class III. The etiology was ischemic in 18 patients and idiopathic dilated in 24. Mitral valve repair was performed in 25 patients, and 17 had mitral valve replacement. The mean logistic EuroSCORE was 33.41. The mean follow-up was 44.52 months. There were no perioperative deaths. Three patients died within 30 days postoperatively. Thirty-day mortality was lower than predicted by EuroSCORE (7.14% vs. 33.41%). The median functional class improved from 3 to 2 during follow-up. Ejection fraction improved from 24% to 42% at 6 weeks, then decreased to 33%. The midterm survival rate was 86%, and 81% after 1 and 2 years. Freedom from reoperation at 2 years was 85%; 6 patients needed reoperation for recurrent mitral regurgitation. Despite high operative risk, mitral valve surgery can be performed successfully with acceptably low mortality in patients with endstage cardiomyopathy. Patients experience substantial clinical improvement and a moderate recovery of left ventricular function.

Choice of the Reference Set in a Randomization Test Based on Linear Ranks in the Presence of Missing Values

The connection between the randomization procedure and analysis is often ignored in the statistical analysis of clinical trials although regulatory guidelines explicitly call upon (ICH E8). Randomization tests comply with these requirements, as they use the applied random allocation to determine the distribution of the test statistic. However, the impact of missing values on randomization tests is not studied up to now. We explore the use of a randomization test when analyzing data of randomized clinical trials with missing values. We will consider two scenarios leading to a reduced or non-reduced reference set depending on handling missing data. Investigations of p-values of randomization tests under normal approximation and, for small sample sizes, exact randomization tests were conducted.

Hämatologische Veränderungen bei Anorexia nervosa im Kindes- und Jugendalter

OBJECTIVE Hematological changes often occur in patients with acute anorexia nervosa (AN). However, the relationship between these disturbances and other clinical parameters remains unclear. METHOD Leucocyte, erythrocyte, and thrombocyte counts as well as hematocrit, hemoglobin, and differential blood counts were collected at admission and after weight restoration in 88 female adolescent patients with the diagnosis of AN according to DSM-IV. These were then compared to clinical parameters. RESULTS At admission, there were mild changes in the blood count, most of which, however, were reversible after weight gain. Patients with a greater weight loss, a lower age-adjusted BMI, and a history of taking psychotropic drugs were more likely to develop hematological abnormalities. CONCLUSIONS Although most of the hematological changes in adolescent patients with AN were mild, patients with high weight loss and/or low age-adjusted BMI as well as those on psychotropic medication should be monitored carefully in order to avoid severe medical complications. An altered immune function in adult patients with chronic AN might contribute to a higher rate of infections and thus to an increased mortality.