Frequency of Miscarriage/Stillbirth and Terminations of Pregnancy Among Women With Congenital Heart Disease in Germany, Hungary and Japan.

BACKGROUND: The 2011 guidelines of the European Society of Cardiology (ESC) on the management of cardiovascular diseases during pregnancy define the maternal predictors for neonatal complications. The aim of this study was to determine whether these are associated with an increased number of miscarriages/stillbirths and terminations of pregnancy (TOPs) also in patients with congenital heart defects (CHD). METHODS AND RESULTS: The 634 women from Germany, Hungary and Japan were surveyed concerning the issues of sexuality and reproductive health, as well as their general life situation and medical care. 25% of the recorded pregnancies in women with CHD resulted in miscarriage, stillbirth or TOP. Affecting 16.8% of all recorded pregnancies, miscarriages or stillbirths occurred more frequently than in the general population and more than previously recorded for patients with CHD. TOP occurred in 8% of the surveyed pregnancies. Underlying maternal predictors for neonatal events had an influence on the number of TOP; among those with underlying predictors, TOP was recorded 3-fold more than in those without such predictors (15.6% vs. 5.5%). Remarkably, a significant deficit regarding the level of information on potential pregnancy-associated risks was observed in all 3 participating countries. CONCLUSIONS: Pregnant women with CHD should always be treated and counseled individually by cardiologists, gynecologists, obstetricians and anesthetists with appropriate expert knowledge. (Circ J 2016; 80: 1846-1851).

Health-related quality of life compared with cardiopulmonary exercise testing at the midterm follow-up visit after tetralogy of Fallot repair: a study of the German competence network for congenital heart defects.

This nationwide study aimed to evaluate health-related quality of life (QoL) experienced by children after tetralogy of Fallot repair and to compare self-reported physical ability with objective exercise performance. This prospective nonrandomized, government-funded multicenter study enrolled 168 patients (70 girls; ages 8-16 years) after tetralogy of Fallot repair at eight German heart centers. Health-related QoL was analyzed by the self-reported KINDL-R quality-of-life questionnaire. The patients' actual exercise capacity was evaluated by a cardiopulmonary exercise test. Health-related QoL and cardiopulmonary exercise capacity were compared with those of an age-matched German standard population. Correlation of health-related QoL with self-estimated physical rating and cardiopulmonary exercise capacity were analyzed. Health-related QoL in children and adolescents after tetralogy of Fallot repair is without limitation. Compared with the standard population, all the items evaluated by the KINDL-R questionnaire showed better or similar values, whereas objective exercise capacity compared with that of the standard population was impaired. Peak oxygen uptake correlated significantly with the physical well-being (p = 0.002) and the total score (p = 0.01) of the KINDL-R questionnaire. Health-related QoL experienced by children and adolescents after tetralogy of Fallot repair is comparable with that of the healthy standard population. However, closer inspection shows that self-estimated physical functioning is significantly overestimated compared with actual exercise capacity. Quality-of-life instruments and exercise tests, therefore, should be used in a complementary manner with children to avoid eventually fatal misinterpretation of patient-estimated physical ability.

Reference values for atrial size and function in children and young adults by cardiac MR: a study of the German competence network congenital heart defects.

PURPOSE: To provide reference data for atrial size and function during childhood and adolescence by cardiac MR (CMR). MATERIALS AND METHODS: We prospectively examined 115 healthy children and adolescents (mean age, 12.4 ± 4.1 years; range, 4.4-20.3 years) by CMR using a stack of standard two-dimensional steady-state free-precession slices acquisition covering the whole heart in transverse plane. Maximal and minimal volumes of both atria and their respective calculated cyclic volume change (CVC) and emptying fraction (EMF) were determined and reference centile curves were computed (lambda-mu-sigma [LMS]-method). RESULTS: Gender differences were noted for atrial volumes and derived parameters. Maximal right atrial (RA) volume for girls was 53.3 ± 11.8 mL/m(2) and 58.1 ± 15.7 for boys (P = 0.064), minimal RA volume for girls/boys was 23.2 ± 6.2/27.0 ± 7.9 mL/m(2) (P = 0.004). Maximal left atrial (LA) volume for girls/boys was 44.2 ± 8.7/46.7 ± 10.1 mL/m(2) (P = 0.143) and minimal LA volume for girls/boys was 19.2 ± 3.9/21.5 ± 5.1 mL/m(2) (P = 0.009). For both atria, CVC was higher for boys, but EMF higher for girls. Percentiles of RA/LA volumes showed steeper increase in boys than in girls, who in fact showed a plateau after age 14. CONCLUSION: Pediatric sex-specific reference centiles are provided to improve clinical interpretation and facilitate future research involving CMR-derived atrial function.

Sentinel lymph node biopsy status is a key parameter to stratify the prognostic heterogeneity of malignant melanoma in high-risk tumors >4.0 mm.

BACKGROUND: The value of sentinel lymph node biopsy (SLNB) as a useful strategy to assess the risk of future metastasis in high-risk melanomas (>4.0 mm) is controversially discussed. OBJECTIVES: In a single-center retrospective study, the prognostic relevance of SLNB and other risk factors in the subgroup of melanomas >4.0 mm was investigated and compared to previously published results. METHODS: Using Kaplan-Meier estimates and Cox regressions, we assessed the prognostic relevance of SLNB in our subcohort of 87 patients with thick melanomas >4.0 mm (T4). The mean follow-up for this subgroup was 51 months. We compared SLN value as compared to ulceration. RESULTS: SLN and ulceration, analyzed as separate risk factors as well as their combination, predicted a highly reduced life expectancy in terms of recurrence-free survival (RFS) in our cohort of patients. SLN, but not ulceration, also predicted overall survival (OS). CONCLUSIONS: Positive SLNB is an essential predictor of RFS and OS in T4 melanoma patients, whereas ulceration lacked significance with respect to OS in our cohort. Our data thus suggest the routine use of SLNB also for T4 melanoma and may therefore allow to optimize risk-stratified therapeutic regimens.

Assessment of interventricular and right-intraventricular dyssynchrony in patients with surgically repaired tetralogy of Fallot by two-dimensional speckle tracking.

AIMS: We aimed to assess interventricular and right-intraventricular dyssynchrony in patients after tetralogy of Fallot (TOF) repair by two-dimensional (2D) speckle tracking and to identify factors associated with dyssynchrony. METHODS AND RESULTS: Forty-two patients after TOF repair with a mean age of 19.8 years and 42 age-matched healthy controls were studied. Longitudinal myocardial deformation (strain) and time-to-peak intervals were assessed by 2D speckle tracking and tissue Doppler imaging (TDI) in an apical four-chamber view. Dyssynchrony was defined as delay above 3 standard deviations of mean values in the control group. Magnetic resonance imaging (MRI) was performed for evaluation of ventricular function. Using 2D speckle tracking, 22 patients (52%) showed interventricular dyssynchrony and 16 (38%) had right-intraventricular dyssynchrony. The interventricular delay correlated significantly with right ventricular (RV) strain (r = 0.687, P < 0.001), RV systolic pressure (r = 0.535, P = 0.001), QRS duration (r = 0.466, P = 0.002), RV end-diastolic (r = 0.377, P = 0.018), and RV end-systolic volumes (r = 0.452, P = 0.004) as well as RV ejection fraction (r = -0.378, P = 0.018). Similarly, the right-intraventricular delay correlated significantly with RV strain (r = 0.534, P < 0.001), QRS duration (r = 0.428, P = 0.005), RV end-systolic volume (r = 0.34, P = 0.038), and RV systolic pressure (r = 0.413, P = 0.015). In multivariate regression analysis, reduced RV strain and prolonged QRS duration remained the main determinant factors predicting dyssynchrony. Moreover, 2D speckle tracking and TDI showed a significant correlation in the assessment of the interventricular (r = 0.738, P < 0.001) and right-intraventricular delay (r = 0.747, P < 0.001). CONCLUSION: Interventricular and right-intraventricular dyssynchrony are detectable in patients after TOF repair by 2D speckle tracking. Reduced RV myocardial deformation and QRS prolongation are the main factors associated with the observed dyssynchrony.

Reduced Biventricular Volumes and Myocardial Dysfunction Long-term After Pediatric Heart Transplantation Assessed by CMR.

BACKGROUND: Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. METHODS: Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). RESULTS: LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (ß = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. CONCLUSIONS: Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

A practical and transferable new protocol for treadmill testing of children and adults.

BACKGROUND: It is just as vital to have an exact overview of the physical fitness of young and growing people as it is for adults. The currently used exercise protocols have limitations in healthy small children, and in senior citizens. In particular with chronically ill patients, regardless of their age, there is a need for an exercise protocol that permits observations over the long term. With this need in mind, we have designed a new transferable standardised exercise protocol, constructing reference values based on improved assessments on a treadmill that permitted stepwise increases of speed and gradient every 90 seconds - the so called treadmill protocol from the German Society of Paediatric Cardiology. OBJECTIVES: We investigated the exercise performance in a healthy Caucasian population ranging in age from 4 to 75 years. METHODS: We measured, using a prospective study design, the distance run, the endurance, and the consumption of oxygen in 548 females and 647 males undergoing an enhanced spiroergometric treadmill protocol in two centres. RESULTS AND CONCLUSIONS: Until puberty, boys and girls have the same indicators of exercise performance. Subsequent to puberty, uptake of oxygen and distance run differ, with males showing higher uptake of oxygen. There is still an age-dependent dynamic of peak uptake of oxygen related to body surface area. Using these new reference values, covering the whole range of age, it proves possible to compare performance during growth and aging of the individual. In this fashion, we have calculated centiles for all recorded variables. External calibration, validation and quality control ensures transferability of our data to other spiroergometry units.

Biventricular dyssynchrony on cardiac magnetic resonance imaging and its correlation with myocardial deformation, ventricular function and objective exercise capacity in patients with repaired tetralogy of Fallot.

BACKGROUND: Electrical dyssynchrony and prolonged QRS duration are common in patients with repaired tetralogy of Fallot (ToF). It has been linked to increased risk of sudden cardiac death and right ventricular (RV) dysfunction. We investigated myocardial dyssynchrony using cardiac magnetic resonance imaging (CMR) and feature tracking analysis (FT) in this setting and compared it to myocardial deformation, conventional parameters of ventricular dysfunction and clinical parameters. METHODS AND RESULTS: Patients underwent standardized CMR investigations as part of a nationwide study. We prospectively assessed myocardial deformation and analysed regional wall motion abnormalities of the RV and the left ventricle (LV) using CMR-FT. The main measure of dyssynchrony was the maximal time difference (wall motion delay) of the regional strain as a parameter of mechanical biventricular dyssynchrony. In addition, clinical parameters and measures of cardiopulmonary exercise capacity were available. Overall 345 patients were included. Parameters of biventricular wall motion delay correlated significantly with global FT-strain parameters (p < 0.0001 for all imaging planes assessed). Furthermore, we found a significant correlation between circumferential RV motion delay and QRS duration (p = 0.006). Higher LV and RV wall motion delay parameters were also associated with lower peak oxygen consumption (p < 0.05) and a worse LV and RV ejection fraction (p < 0.02). CONCLUSIONS: Assessment of mechanical dyssynchrony is feasible using CMR-FT in ToF patients. Parameters of mechanical dyssynchrony correlate with electrical dyssynchrony, biventricular function and objective exercise capacity in this setting. Due to the weak degree of correlation, however, the clinical significance of these findings remains to be clarified by further studies.

The expression of low density lipoprotein receptor-related protein in colorectal carcinoma.

Low density lipoprotein receptor-related protein (LRP) is a multifunctional cell surface receptor binding many different ligands including proteinases and their inhibitors, some of which are known to be involved in tumor biology. We studied the expression of LRP and its putative role in colorectal carcinoma. Tissue samples were obtained from 50 patients with colorectal carcinoma and fixed in formalin and embedded in paraffin. Immunohistochemical staining was performed using antibodies directed against LRP, cathepsin B and urokinase-type plasminogen activator (u-PA). The expression of LRP was further studied by polymerase chain reaction. The TNM stage was determined according to UICC guide lines and was based upon histological analysis. LRP was primarily expressed in stroma cells [36 patients (72%)] and less frequently in tumor cells [6 patients (12%)]. In 22% of all cases LRP was prominent at the invasion front. Cathepsin B was found both in the tumor stroma [50 (100%)] and in the tumor cells [46 (92%)]. u-PA was present in the tumor stroma [44 (88%)] and in the tumor cells [44 (88%)]. In stromal cells the expression of LRP correlated significantly with the expression of u-PA (p=0.043). Furthermore, the expression of LRP and of u-PA in tumor cells correlated with the tumor stage according to UICC (p=0.038 and 0.018, respectively). We provide evidence that LRP is expressed in colorectal cancer. As LRP forms complexes with u-PA and its inhibitor, we suspect that LRP can influence the known effects of u-PA on tumor biology.

DAPK promotor methylation is an early event in colorectal carcinogenesis.

Death-associated protein kinase (DAPK) is frequently inactivated by promotor hypermethylation in various human cancers. At present, little is known about the significance of DAPK inactivation in colorectal carcinogenesis. We therefore, investigated macrodissected samples of 22 formalin-fixed and paraffin-embedded T1-carcinomas showing normal colon mucosa, intraepithelial neoplasia and carcinoma tissue on the same slice. Dissected carcinoma areas showed a higher frequency of DAPK promotor methylation (81.2%) compared to intraepithelial neoplasia (68.2%). Colon mucosa adjacent to intraepithelial neoplasia or carcinoma showed DAPK promotor methylation in only two of eight cases (25%). We suggest that DAPK promotor hypermethylation may play an important role in the early steps of tumor progression in colorectal carcinoma.

The number of lymph node metastases in gastric cancer correlates with the angiotensin I-converting enzyme gene insertion/deletion polymorphism.

PURPOSE: In the present study, we aimed to substantiate the putative significance of angiotensin I-converting enzyme (ACE) on gastric cancer biology by investigating the influence of its gene polymorphism on gastric cancer progression. EXPERIMENTAL DESIGN: Genomic DNA was purified from peripheral blood mononuclear cells or tissue specimens. Amplified ACE gene fragments were separated on agarose gels. D or I alleles were identified by the presence of 190- or 490-bp fragments, respectively. Local expression of ACE was investigated by immunohistochemistry. RESULTS: Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype. The distribution of the ACE genotypes did not differ significantly from the control group of 189 patients without gastric cancer. However, the ACE genotypes correlated with the number of lymph node metastases and the Unio Internationale Contra Cancrum (UICC) tumor stage. Patients with the II genotype had a highly significantly smaller number of lymph node metastases (P < 0.001) and a significantly lower UICC tumor stage (P = 0.01) than patients with the DD genotype. No correlation was found between tumor type, tumor location, local tumor growth, distant metastases, and the ACE genotype. The expression of ACE in gastric cancer was investigated by immunohistochemistry in 100 of 113 patients. ACE was expressed by endothelial cells in all (100%) specimens and by tumor cells in 56 (56%) specimens. CONCLUSIONS: Our study shows that ACE is expressed locally in gastric cancer and that the gene polymorphism influences metastatic behavior.

Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study.

Despite clearly defined histologic criteria, the prediction of tumor behavior for patients with gastrointestinal stromal tumors (GIST) still poses a challenge to pathologists. Therefore, searching for alternative markers that allow for better prognostic evaluation is an important task. To determine the practicability of immunohistochemical staining for p16 in clinical cases, we examined p16 protein expression in a group of 284 GISTs, a subset of which had long-term follow-up (median, 45 months; range, 1-204 months). P16 protein expression was ascertained on tissue microarrays as well as on standard sections. Survival analyses were carried out in 157 patients. P16 loss was found in 50% of GISTs, there being no correlation with age, sex, histologic subtype, signs of necrosis, or metastases. Patients having p16-negative tumors had a worse prognosis than those with p16-positive tumors (P = 0.012) with a 2.3-fold relative increased risk of dying of disease. P16 loss identified a subgroup of gastric tumors with a worse prognosis (P = 0.03). The multivariate configural frequency analysis identified two "antitypes," whose observed frequency was found to be significantly lower than the expected frequency [i.e., marker combinations: p16 positive, no metastases, and death of disease and p16 loss, metastases, and still alive]. The "type" whose observed frequency was significantly higher than the expected frequency consisted of the following marker pattern: p16 loss, necrosis, and death of disease (P < 0.001). In the multivariate Cox regression analysis, p16 loss, necrosis, and metastases each had independent prognostic value. P16 loss is a common molecular abnormality in GISTs and might be used in routine diagnosis to identify patients with high-risk tumors.

Myocardial deformation parameters predict outcome in patients with repaired tetralogy of Fallot.

BACKGROUND: Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function and to predict outcome in repaired tetralogy of Fallot (ToF). We aimed to test the hypothesis that parameters of myocardial deformation on cardiac MRI (CMR) relate to symptoms and provide prognostic information in patients with repaired ToF. METHODS AND RESULTS: We included 372 patients with ToF (median age 16 years; 55% male), recruited within a nationwide, prospective study. Longitudinal (LS), circumferential (CS) and radial global strain (RS) were analysed by CMR-based feature tracking (FT). A combined endpoint of death, successful resuscitation or documented ventricular tachycardia was employed. Parameters of global strain were associated with New York Heart Association (NYHA) class and symptomatic deterioration. During a median follow-up of 7.4 years, 20 events occurred. Left ventricular (LV) CS and right ventricular (RV) LS emerged as predictors of outcome, independent of QRS duration, LV/RV ejection fraction and volumes, NYHA class and peak oxygen uptake. In combination, these parameters also identified a subgroup of patients at significantly increased risk of adverse of outcomes (HR 3.3, p=0.002). Furthermore, LV LS, RS, CS and RV LS were related to the risk of death and nearly missed death (p<0.05 for all). CONCLUSIONS: FT-CMR provides myocardial deformation parameters, easily derived from standard CMR studies. They relate to symptoms and clinical deterioration in patients with ToF. More importantly, they predict adverse outcome independent of established risk markers, and should be considered as a useful adjunct to established outcome predictors, especially in younger patients with ToF. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov: NCT00266188; Results.

Atrial amyloidosis: an arrhythmogenic substrate for persistent atrial fibrillation.

BACKGROUND: Structural changes, like atrial fibrosis, may increase the likelihood of atrial fibrillation (AF) occurring in response to triggering events. The influence of isolated atrial amyloidosis (IAA) is largely unknown. METHODS AND RESULTS: Right atrial appendages (1 or 2 entire cross sections) were obtained from 245 patients undergoing open-heart surgery. Atrial amyloid was identified by Congo red staining and classified by immunohistochemistry. Amyloid was found in 40 (16.3%) of 245 patients, and all deposits were immunoreactive for atrial natriuretic peptide (ANP). Thirty-eight (15.5%) patients suffered from persistent AF. The presence of amyloid correlated with age and P-wave duration and was related to sex, valve diseases, and the presence of AF (P<0.01). The association between atrial amyloid, AF, and P-wave duration was independent of age and sex. According to multiple logistic regression analysis, amyloid was the only age- and sex-independent predictor for the presence of AF. Atrial fibrosis was not a predictor for AF, and the amount of amyloid correlated inversely with the degree of interstitial fibrosis (P=0.001; r=-0.55). CONCLUSIONS: Our study provides evidence that IAA affects atrial conduction and increases the risk of AF. The occurrence of IAA depends on age leading to the formation of an amyloid nidus. The progression and consequences of IAA are then influenced by pathological conditions, such as valve diseases, that increase synthesis and secretion of ANP. The inverse correlation between IAA and atrial fibrosis suggests that these patients may not benefit from treatment with ACE inhibitors to reduce the amount of atrial fibrosis.

High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) represent a distinctive (but histologically heterogeneous) group of neoplasms, the malignant potential of which is often uncertain. To determine the prognostic relevance of p16INK4 alterations in GISTs, we investigated a larger group of GISTs and correlated the genetic findings with clinicopathological factors and patient survival. MATERIAL AND METHODS: We evaluated the methylation status of the promotor by methylation-specific polymerase chain reaction (PCR), the presence of mutations by PCR-SSCP-sequencing, the loss of heterozygosity at the p16INK4 locus (using the c5.1 marker), and the immunohistochemical expression of p16INK4 protein in 43 GISTs in 39 patients. RESULTS: p16INK4 alterations were found in 25 of 43 GISTs (58.1%), with benign, borderline, or malignant GISTs showing no differences in the type and frequency of alteration. p16INK4 alterations were correlated with a loss of p16INK4 protein expression (P <.01). Patients who had tumors with p16INK4 alterations had a poorer prognosis than patients with tumors without such alterations (P =.02). There was a high predictive value for p16INK4 alterations only in the group of benign and borderline GISTs (P <.01) with regard to clinical outcome. Univariate Cox's proportional hazard regression analysis revealed a strong correlation between p16INK4 alterations, tumor size, mitotic index, and overall survival (P <.02), whereas multivariate Cox's analysis confirmed only p16INK4 alterations as an independent prognostic factor. CONCLUSION: We believe that the evaluation of p16INK4 alteration status is a helpful prognosticator, particularly in the benign and borderline groups of GISTs.

Influence of chronic exposure to organic solvent mixtures on contrast sensitivity in silk-screen printers: matched-pair analysis.

The aim of the study was the determination of the influence of chronic occupational exposure to organic solvent mixtures on the contrast sensitivity (CS) of silk-screen printers. Contrast sensitivity was measured for 28 matched (age, sex) pairs of silk-screen printers and controls using the Vision Contrast Test System - VCTS 6500 chart. The duration of exposure to industrial neurotoxic substances was about 9 years. Contrast sensitivity impairments were recorded in 28.6% of the printers for both eyes at several spatial frequencies. Males and females differed in CS significantly, but no interaction between gender (male vs. female) and exposure (printers vs. controls) was found.

Determinants and consequences of atrial fibrosis in patients undergoing open heart surgery.

OBJECTIVE: Atrial fibrillation (AF) is a frequent complication following open-heart surgery (OHS). Increased atrial fibrosis may indicate the presence of an intrinsic arrhythmogenic substrate. The aim of this prospective study was to determine whether atrial fibrosis is associated with increased prevalence of AF after OHS. METHODS: Right atrial appendages were obtained from 259 patients undergoing OHS; none of the patients had a history of AF. Atrial fibrosis was quantitatively analyzed with point counting. All patients were followed prospectively until hospital discharge. None of the patients received anti-arrhythmic prophylaxis. Post-operative AF was defined as an episode of AF lasting > or = 5 min. RESULTS: Quantitation of atrial fibrosis yielded a mean volume percentage of 15.8 +/- 4.3% (V%; range 4.6-32.4%). Patient age was found to correlate with the amount of atrial fibrosis (r = 0.165; P < 0.01) and surface P-wave duration (r = 0.249; P < 0.01). The degree of fibrosis combined with P-wave duration predicted post-operative AF (P < 0.01). Age (> 60 years) and P-wave duration (> or = 100 ms) were independent predictors of post-operative AF (age: relative risk 2.20; P-wave: relative risk 2.69; P < 0.05). The patients were divided into three groups: group 1, V% = 4.6-13.8%; group 2, V% = 13.9-23.1%; group 3, V% = 23.2-32.4%. A total of 52 patients (20.1%) developed AF, which occurred least commonly in group 1 (16.3%) and group 2 (21.2%) as compared with group 3 (33.3%). CONCLUSIONS: Atrial fibrosis provides a pathophysiological substrate for post-operative AF. The results support the importance of P-wave duration as a predictor of post-operative AF, and explain the increased prevalence of AF in elderly patients after OHS.

Importance of CMR within the Task Force Criteria for the diagnosis of ARVC in children and adolescents.

BACKGROUND: Cardiac magnetic resonance (CMR) is a component of the revised Task Force Criteria (rTFC) for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, its diagnostic value in a pediatric population is unknown. OBJECTIVES: This study examined the contribution of CMR to diagnosing ARVC using the rTFC in a pediatric population. METHODS: Clinical CMR studies of 142 pediatric patients evaluated for ARVC between 2005 and 2009 were reviewed. Patients were categorized into "definitive," "borderline," "possible," or "no" ARVC diagnostic groups based on the rTFC. The extent to which each element of the rTFC contributed to diagnosing ARVC was determined using a c-statistics model. RESULTS: A total of 23 (16%), 32 (23%), 37 (26%), and 50 (35%) patients had definite, borderline, possible, and no ARVC, respectively, applying the rTFC. The prevalence of regional wall motion abnormalities in these groups was 83%, 53%, 22%, and 16%, respectively (p < 0.001). By CMR, right ventricular end-diastolic volumes were 118 ± 31 cc/m², 108 ± 22 cc/m², 94 ± 14 cc/m², and 92 ± 18 cc/m², respectively (p < 0.001). Right ventricular fatty infiltration and fibrosis were detected in only 1 and 3 patients, respectively, all of whom had definitive ARVC. Of all rTFC major criteria, CMR had the largest c-statistic decline (c = -0.163). Eleven of the 23 patients (48%) with definite ARVC would not have been in this group if CMR had not been performed. CONCLUSIONS: CMR parameters are important contributors to a diagnosis of ARVC in children, using the rTFC. Fatty infiltration and myocardial fibrosis provide limited value in children and adolescents.

Selective loss of codon 72 proline p53 and frequent mutational inactivation of the retained arginine allele in colorectal cancer.

According to recent reports, some cancer types exhibit nonrandom allele loss at codon 72 in exon 4 of the p53 gene [coding for proline (72Pro) or arginine (72Arg)]. To clarify this phenomenon for colorectal cancer and to find out if this preferential loss might have any functional significance, p53 loss of heterozygosity (LOH) and p53 mutations were investigated in a group of 61 colorectal cancers and 28 liver metastases, and were correlated with clinicopathologic factors. A comparison of a patient's blood codon 72 status with a healthy control group did not reveal an enhanced risk of developing colorectal tumors for one of the two isoforms. p53-LOH and p53 mutations were found in 62.2% and 39.4% of primary tumors, respectively, and in 57.9% and 25% of hepatic metastases, respectively. In 14 heterozygous cases showing exon 4-LOH, only the 72Pro allele was lost and the retained 72Arg was preferentially mutated. In general, p53 mutations were significantly associated with the 72Arg tumor status (P < .001). Distal tumors showed allelic losses of the p53 gene more commonly than proximal tumors (P = .054). The prevalence of 72Arg increased in frequency with higher Dukes stage (P = .056). We suggest that either the preferential loss of 72Pro or the mutation of the 72Arg in colorectal cancer and hepatic metastases is associated with malignant potential and might reflect carcinogenic exposure, particularly in the distal part of the large intestines.

Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma.

Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors.