Electrocardiographic characteristics of patients with Ebstein's anomaly before and after ablation of an accessory atrioventricular pathway

UNLABELLED The abnormal development of the tricuspid valve in patients with Ebstein's anomaly results in several activation abnormalities including delayed intraatrial conduction, right bundle branch block (RBBB), and ventricular preexcitation. The aim of the present study was to define the ECG characteristics before and after ablation of an accessory A-V pathway (AP) in patients with Ebstein's anomaly. METHODS A series of 226 consecutive patients with Ebstein's anomaly was studied. Sixty-four patients (28%) had documented tachycardia. Thirty-three patients with recurrent tachycardia were found to have a single right-sided AP that was successfully ablated (study group). Thirty patients without tachycardia served as the control group. RESULTS Only 21 of 33 patients (62%) had a typical ECG pattern of preexcitation. In addition, none of the patients had an ECG pattern of RBBB during sinus rhythm. In contrast, 28 of 30 (93%) patients in the control group had RBBB (P < 0.001). Radiofrequency catheter ablation resulted in appearance of RBBB in 31 of 33 (94%) patients. The absence of RBBB in patients with Ebstein's anomaly and recurrent tachycardia had a 98% sensitivity and 92% specificity for the diagnosis of an AP. The positive predictive value was 91% (0.77, 0.97 CI 95%) and the negative predictive value was 98% (0.85, 0.99 CI 95%). CONCLUSION One-third of patients with Ebstein's anomaly and symptomatic tachyarrhythmias have minimal or absent ECG features of ventricular preexcitation. In these patients, the absence of RBBB pattern is a strong predictor of an AP.

Value of different follow-up strategies to assess the efficacy of circumferential pulmonary vein ablation for the curative treatment of atrial fibrillation.

BACKGROUND The objective of this study was to compare transtelephonic ECG every 2 days and serial 7-day Holter as two methods of follow-up after atrial fibrillation (AF) catheter ablation for the judgment of ablation success. Patients with highly symptomatic AF are increasingly treated with catheter ablation. Several methods of follow-up have been described, and judgment on ablation success often relies on patients' symptoms. However, the optimal follow-up strategy objectively detecting most of the AF recurrences is yet unclear. METHODS Thirty patients with highly symptomatic AF were selected for circumferential pulmonary vein ablation. During follow-up, a transtelephonic ECG was transmitted once every 2 days for half a year. Additionally, a 7-day Holter was recorded preablation, after ablation, after 3 and 6 months, respectively. With both, procedures symptoms and actual rhythm were correlated thoroughly. RESULTS A total of 2,600 transtelephonic ECGs were collected with 216 of them showing AF. 25% of those episodes were asymptomatic. On a Kaplan-Meier analysis 45% of the patients with paroxysmal AF were still in continuous SR after 6 months. Simulating a follow-up based on symptomatic recurrences only, that number would have increased to 70%. Using serial 7-day ECG, 113 Holter with over 18,900 hours of ECG recording were acquired. After 6 months the percentage of patients classified as free from AF was 50%. Of the patients with recurrences, 30-40% were completely asymptomatic. The percentage of asymptomatic AF episodes stepwise increased from 11% prior ablation to 53% 6 months after. CONCLUSIONS The success rate in terms of freedom from AF was 70% on a symptom-only-based follow-up; using serial 7-day Holter it decreased to 50% and on transtelephonic monitoring to 45%, respectively. Transtelephonic ECG and serial 7-day Holter were equally effective to objectively determine long-term success and to detect asymptomatic patients.

Topographic variability of the esophageal left atrial relation influencing ablation lines in patients with atrial fibrillation.

UNLABELLED Topography of the esophagus in atrial fibrillation ablation. INTRODUCTION The close anatomic relationship of the posterior wall of the left atrium (LA) and the thermosensitive esophagus creates a potential hazard in catheter ablation procedures. METHODS AND RESULTS In 30 patients (pts) with atrial fibrillation (AF) undergoing catheter ablation, we prospectively studied the course and contact of the esophagus in relation to LA and the topographic proximity to ablation lines encircling the right-sided and left-sided pulmonary veins (PV) as well as to the posterior line connecting the encircling lines using the electromagnetic mapping system for reconstruction of LA and for tagging of the esophagus. This new technique of anatomic tagging of the esophagus was validated against the CT scan as a standard imaging procedure. The esophageal course was highly variable, extending from courses in direct vicinity to the left- or right-sided PV as well as in the midportion of the posterior LA. In order to avoid energy application in direct proximity to the esophagus, adjustments of the left and right PV encircling lines were necessary in 14/30 pts (47%) and 3/30 (10%). In 30 pts (100%), the mid- to inferior areas of the posterior LA revealed contact with the esophagus. Therefore, posterior and inferior linear ablation lines were abandoned and shifted to superior in 29 pts (97%). CONCLUSIONS Anatomic tagging of esophagus revealed a highly variable proximity to different areas of the posterior LA suggesting individual adjustment of encircling and linear ablation lines in AF ablation procedures to avoid the life threatening complication of esophagus perforation.

Stable secondary arrhythmias late after intraoperative radiofrequency ablation of atrial fibrillation: incidence, mechanism, and treatment.

INTRODUCTION Intraoperative radiofrequency (RF) ablation is an effective treatment of atrial fibrillation (AF). However, secondary arrhythmias late after ablation may complicate the patient's course. We report on the incidence, mechanisms, and treatment of gap-related atrial flutter and other secondary arrhythmias during long-term follow-up. METHODS AND RESULTS In 129 patients who underwent intraoperative RF ablation with placement of left atrial linear lesions using minimally invasive surgical techniques, secondary arrhythmias were analyzed during long-term follow-up (20 +/- 6 months). Transient atrial arrhythmias during the first 3 postoperative months were excluded. In 8 (6.2%) of 129 patients, sustained stable secondary arrhythmias were documented. Left atrial, gap-related atrial flutter was observed in 4 patients (3.1%). The flutter was treated by percutaneous RF ablation in 3 patients (2.3%) and with drugs in 1 patient (0.8%). In 2 patients (1.6%), right atrial isthmus-dependent atrial flutter occurred and was treated successfully by percutaneous RF ablation. In 2 patients (1.6%), ectopic right atrial tachycardias occurred and were treated with percutaneous RF ablation. CONCLUSION Late after intraoperative RF ablation of atrial fibrillation, three types of stable secondary arrhythmias were observed in 6% of patients: left atrial gap-related atrial flutter, right atrial isthmus-dependent atrial flutter, and ectopic atrial tachycardia. Gaps after intraoperative RF ablation due to noncontinuous or nontransmural linear lesions may lead to stable left atrial macroreentrant tachycardias, requiring new interventional therapy.

Impact of cardiac computed tomography of the interatrial septum before pulmonary vein isolation

BACKGROUND Multidetector computed tomography (MDCT) may be useful to identify patients with patent foramen ovale (PFO). The aim of this study was to analyze whether a MDCT performed before pulmonary vein isolation reliably detects a PFO that may be used for access to the left atrium. METHODS AND RESULTS In 79 consecutive patients, who were referred for catheter ablation of symptomatic paroxysmal or persistent atrial fibrillation (AF), the presence of a PFO was explored by MDCT and transesophageal echocardiography (TEE). TEE was considered as the gold standard, and quality of TEE was good in all patients. In 16 patients (20.3%), MDCT could not be used for analysis because of artifacts, mainly because of AF. On TEE, a PFO was found in 15 (23.8%) of the 63 patients with usable MDCT. MDCT detected six PFO of which four were present on TEE. This corresponded to a sensitivity of 26.7%, a specificity of 95.8%, a negative predictive value of 80.7%, and a positive predictive value of 66.7%. The receiver operating characteristics curve of MDCT for the detection of PFO was 0.613 (95% confidence interval 0.493-0.732). CONCLUSIONS MDCT may detect a PFO before pulmonary isolation. However, presence of AF may lead to artifacts on MDCT impeding a meaningful analysis. Furthermore, in this study sensitivity and positive predictive value of MDCT were low and therefore MDCT was not a reliable screening tool for detection of PFO.

Positive Affect and Sleep in Spousal Alzheimer Caregivers: A Longitudinal Study.

This article examines the longitudinal relation between positive affect (PA) and sleep in 126 spousal Alzheimer's disease caregivers. Caregivers underwent 4 yearly assessments for the Positive and Negative Affect Schedule, the self-rated Pittsburgh Sleep Quality Index, and actigraphy to objectify nighttime total sleep time, wake after sleep onset, and percentage of sleep. Increased levels of PA and a greater positivity (i.e., positive-to-negative affect) ratio were significantly associated with better subjective sleep over the entire study period. Yearly increases in PA-even when controlling for negative affect (NA)-and in the positivity ratio were also associated with better subjective sleep. PA and actigraphy measures showed no significant relations. Increased PA is longitudinally associated with better sleep in dementia caregivers largely independent of NA.

Presencia y latencia del diablo en tres comedias de Agustín Moreto

In this paper, we analyze the dramatic configuration of the devil in three plays by Agustín Moreto, Los siete durmientes (1651) El más ilustre francés, San Bernardo (1657) y El azote de su patria (1669). The main prospect is not only the study of the stage power of a character with such a wide range of theatrical and artistic possibilities, but also his structural role in the conflict and his decisive influence on the action even when he is not actually present.

Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.

The development of lymph nodes (LNs) and formation of LN stromal cell microenvironments is dependent on lymphotoxin-β receptor (LTβR) signaling. In particular, the LTβR-dependent crosstalk between mesenchymal lymphoid tissue organizer and hematopoietic lymphoid tissue inducer cells has been regarded as critical for these processes. Here, we assessed whether endothelial cell (EC)-restricted LTβR signaling impacts on LN development and the vascular LN microenvironment. Using EC-specific ablation of LTβR in mice, we found that conditionally LTβR-deficient animals failed to develop a significant proportion of their peripheral LNs. However, remnant LNs showed impaired formation of high endothelial venules (HEVs). Venules had lost their cuboidal shape, showed reduced segment length and branching points, and reduced adhesion molecule and constitutive chemokine expression. Due to the altered EC-lymphocyte interaction, homing of lymphocytes to peripheral LNs was significantly impaired. Thus, this study identifies ECs as an important LTβR-dependent lymphoid tissue organizer cell population and indicates that continuous triggering of the LTβR on LN ECs is critical for lymphocyte homeostasis.

Placing unprecedented recent fir growth in a European-wide and Holocene-long context

Forest decline played a pivotal role in motivating Europe's political focus on sustainability around 35 years ago. Silver fir (Abies alba) exhibited a particularly severe dieback in the mid-1970s, but disentangling biotic from abiotic drivers remained challenging because both spatial and temporal data were lacking. Here, we analyze 14 136 samples from living trees and historical timbers, together with 356 pollen records, to evaluate recent fir growth from a continent-wide and Holocene-long perspective. Land use and climate change influenced forest growth over the past millennium, whereas anthropogenic emissions of acidic sulfates and nitrates became important after about 1850. Pollution control since the 1980s, together with a warmer but not drier climate, has facilitated an unprecedented surge in productivity across Central European fir stands. Restricted fir distribution prior to the Mesolithic and again in the Modern Era, separated by a peak in abundance during the Bronze Age, is indicative of the long-term interplay of changing temperatures, shifts in the hydrological cycle, and human impacts that have shaped forest structure and productivity.

Evidence of species-specific neighborhood effects in the dipterocarpaceae of a Bornean rain forest

Although accumulating evidence indicates that local intraspecific density-dependent effects are not as rare in species-rich communities as previously suspected, there are still very few detailed and systematic neighborhood analyses of species-rich communities. Here, we provide such an analysis with the overall goal of quantifying the relative importance of inter- and intraspecific interaction strength in a primary, lowland dipterocarp forest located at Danum, Sabah, Malaysia. Using data on 10 abundant overstory dipterocarp species from two 4-ha permanent plots, we evaluated the effects of neighbors on the absolute growth rate of focal trees (from 1986 to 1996) over increasing neighborhood radii (from 1 to 20 m) with multiple regressions. Only trees 10 cm to < 100 cm girth at breast height in 1986 were considered as focal trees. Among neighborhood models with one neighbor term, models including only conspecific larger trees performed best in five out of 10 species. Negative effects of conspecific larger neighbors were most apparent in large overstory species such as those of the genus Shorea. However, neighborhood models with separate terms and radii for heterospecific and conspecific neighbors accounted for more variability in absolute growth rates than did neighborhood models with one neighbor term. The conspecific term was significant for nine out of 10 species. Moreover, in five out of 10 species, trees without conspecific neighbors had significantly higher absolute growth rates than trees with conspecific neighbors. Averaged over the 10 species, trees without conspecific neighbors grew 32.4 cm(2) in basal area from 1986 to 1996, whereas trees with conspecific neighbors only grew 14.7 cm(2) in basal area, although there was no difference in initial basal area between trees in the two groups. Averaged across the six species of the genus Shorea, negative effects of conspecific larger trees were significantly stronger than for heterospecific larger neighbors. Thus, high local densities within neighborhoods of 20 m may lead to strong intraspecific negative and, hence, density-dependent, effects even in species rich communities with low overall densities at larger spatial scales. We conjecture that the strength of conspecific effects may be correlated with the degree of host specificity of ectomycorrhizae.

What Makes a Family Firm Innovative? CEO Risk-Taking Propensity and the Organizational Context of Family Firms

Investigating the new product portfolio innovativeness of family firms connects two important topics that have recently received considerable attention in innovation and family firm research. First, new product portfolio innovativeness has been identified as a critical determinant of firm performance. Second, research on family firms has focused on the questions of if and why family firms are more or less innovative than other organizational forms. Research investigating the innovativeness of family firms has often applied a risk-oriented perspective by identifying socioemotional wealth (SEW) as the main reference that determines firm behavior. Thus, prior research has mainly focused on the organizational context to predict innovation-related family firm behavior and neglected the impact of preferences and the behavior of the chief executive officer (CEO), which have both been shown to affect firm outcomes. Hence, this study aims to extend the previous research by introducing the CEO's disposition to organizational context variables to explain the new product portfolio innovativeness of small and medium-sized family firms. Specifically, this study explores how the organizational context (i.e., ownership by top management team [TMT] family members and generation in charge of the family firm) of family firms interacts with CEO risk-taking propensity to affect new product portfolio innovativeness. Using a sample of 114 German CEOs of small and medium-sized family firms operating in manufacturing industries, the results show that CEO risk-taking propensity has a positive effect on new product portfolio innovativeness. Moreover, the analyses show that the organizational context of family firms impacts the relationship between CEO risk-taking propensity and new product portfolio innovativeness. Specifically, the relationship between CEO risk-taking propensity and new product portfolio innovativeness is weaker if levels of ownership by TMT family members are high (high SEW). Additionally, the effect of CEO risk-taking propensity on new product portfolio innovativeness is stronger in family firms at earlier generational stages (high SEW). This result suggests that if SEW is a strong reference, family firm-specific characteristics can affect individual dispositions and, in turn, the behaviors of executives. Therefore, this study helps extend the knowledge on the determinants of new product portfolio innovativeness of family firms by considering an individual CEO preference and the organizational context variables of family firms simultaneously.

Epithelial NAIPs protect against colonic tumorigenesis.

NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6(Δ/Δ)), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6(Δ/Δ) mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6(Δ/Δ) mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6(Δ/Δ) mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6(Δ/Δ) mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis.

Thromboxane A2 acts as tonic immunoregulator by preferential disruption of low-avidity CD4+ T cell-dendritic cell interactions

Interactions between dendritic cells (DCs) and T cells control the decision between activation and tolerance induction. Thromboxane A2 (TXA2) and its receptor TP have been suggested to regulate adaptive immune responses through control of T cell-DC interactions. Here, we show that this control is achieved by selectively reducing expansion of low-avidity CD4(+) T cells. During inflammation, weak tetramer-binding TP-deficient CD4(+) T cells were preferentially expanded compared with TP-proficient CD4(+) T cells. Using intravital imaging of cellular interactions in reactive peripheral lymph nodes (PLNs), we found that TXA2 led to disruption of low- but not high-avidity interactions between DCs and CD4(+) T cells. Lack of TP correlated with higher expression of activation markers on stimulated CD4(+) T cells and with augmented accumulation of follicular helper T cells (TFH), which correlated with increased low-avidity IgG responses. In sum, our data suggest that tonic suppression of weak CD4(+) T cell-DC interactions by TXA2-TP signaling improves the overall quality of adaptive immune responses.