Atrial Septal Versus Atrial Appendage Pacing:

HERMIDA, J.-S., et al. : Atrial Septal Versus Atrial Appendage Pacing: Feasibility and Effects on Atrial Conduction, Interatrial Synchronization, and Atrioventricular Sequence. Atrial septal (Se-P) and atrial appendage pacing (Ap-P) were compared in a randomized, controlled study to assess the feasibility, the reliability, and the effects of Se-P on atrial conduction, interatrial synchronization, and the AV sequence. The main baseline characteristics of the patients were comparable in both groups. There was no difference in feasibility or reliability between the two techniques. Compared to Ap-P   (n = 28)   , Se-P   (n = 28)   decreased the P wave duration, left atrial electromechanical delay (LAEMD), and interatrial interval (−1.6% vs   +28%, P < 0.001; −3%   vs   + 30%, P < 0.001; −130%   vs   + 78%, P < 0.001   ); it induced a smaller increase of the right AEMD, a slight reversal of the timing of the atrial systoles and a shortening of the PR interval (−13% vs   + 25%, P < 0.001   ) and of the interval separating atrial systoles from ventricular activation. Finally, the shortening of the PR interval was smaller during high Se-P versus low Se-P. Se-P avoids the undesirable prolongation of the atrial, interatrial, and AV conductions observed during Ap-P. In addition, Se-P creates a slight reversal of the timing of the atrial systoles and induces a shortening of PR interval, the extent of which could depend on the height of the pacing site on the septum. (PACE 2003; 26[Pt. I]:26–35)     

Binding of factor VIIa to the endothelial cell protein C receptor reduces its coagulant activity

BACKGROUND: Endothelial cell protein C receptor (EPCR) binds protein C through its gamma-carboxyglutamic acid (Gla) domain and enhances its thrombin-thrombomodulin complex-dependent activation. So far, only protein C/activated protein C has been shown to interact with EPCR. Factor VII (FVII), the coagulation trigger upon tissue factor (TF) interaction, is a serine protease whose Gla domain is highly homologous to the Gla domain of protein C. OBJECTIVES: To characterize the binding of FVII/FVIIa to EPCR and its functional consequences. METHODS AND RESULTS: We demonstrated by surface plasmon resonance (SPR) that FVII/FVIIa binds to EPCR through its Gla domain. At therapeutic concentrations, FVIIa reduced the activation of protein C by 40%. Soluble EPCR (sEPCR) was also able to prolong dose-dependently the clotting time induced by the FVIIa-TF complex. SPR and amidolytic experiments showed that FVIIa is able to interact simultaneously with TF and EPCR, thus ruling out the possibility that the effect of EPCR on clotting time was due to the inhibition of the binding between FVIIa and TF. sEPCR inhibited dose-dependently the activation of FX by the FVIIa-TF complex. Notably, blocking the binding site of EPCR on the endothelial surface increased the generation of FXa 2-fold. CONCLUSIONS: EPCR binds to FVII/FVIIa and inhibits the procoagulant activity of the FVIIa-TF complex.     

The Anatomic Impact of Sequential,Additional, Ostial Radiofrequency Ablation Following Pulmonary Vein Cryo‐Isolation

Background : Although pulmonary vein (PV) stenosis is a serious complication of radiofrequency PV isolation, the anatomical impact of a combination of two energy sources on PV diameter has not been evaluated. The aim of this study was to evaluate the impact of supplementary point‐by‐point radiofrequency applications (following PV cryoablation) on the PV orifice diameter. Methods : Forty‐nine patients having undergone PV isolation for drug‐refractory atrial fibrillation were included. All had undergone cardiac computed tomography before ablation and again at least 3 months afterwards. When isolation with the cryoballoon was not complete, a conventional irrigated‐tip radiofrequency catheter was used for point‐by‐point applications. Results : Of the 189 target PVs, 117 were isolated with cryotherapy alone (cryo PVs) and 72 required additional radiofrequency (hybrid PVs). The second scan (performed an average of 11.4 ± 5.4 months after) showed a decrease in diameter for all the hybrid PVs (17.2 ± 2.6 to 16.3 ± 3.4 mm; P = 0.037) but no change for the cryo PVs. This change was associated with a decrease in left superior pulmonary vein (LSPV) diameter (19.2 ± 3.0 to 17.8 ± 4.9 mm, P = 0.014). There were no changes in other veins. A subgroup analysis for the LSPV revealed a decrease for the hybrid PVs (18.8 ± 3.6 to 15.9 ± 7.1 mm, P = 0.046) but not for the cryo PVs. Significant PV stenosis was observed in three hybrid PVs (two severe stenosis of the LSPV and one moderate stenosis of the right inferior pulmonary vein) but not in cryo PVs (4.1% vs 0%, respectively; P = 0.023). Conclusions : Cryoballoon ablation of the PV with adjunct, focal, irrigated ostial RF applications may be associated with a higher risk of PV stenosis. (PACE 2012;35:1420–1427)     

Ropinirole-Induced Symptomatic Sinus Node Dysfunction

Restless legs syndrome is a neurological disorder that can be treated with ropinirole. We report the case of a patient who presented with syncope during treatment with ropinirole due to prolonged sinus pauses. The treatment was discontinued and the patient remained asymptomatic. Ropinirole may induce symptomatic sinus pauses in patients without organic sinus node dysfunction.     

Autoantibodies against the endothelial receptor of protein C are associated with acute myocardial infarction in young women

BACKGROUND: Acute myocardial infarction (AMI) is rare among young women. The search for unknown risk factors is warranted. Endothelial protein C receptor (EPCR) is largely present at the endothelial surface of large arteries. No studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are available. METHODS: Plasma IgA, IgM and IgG anti-EPCR levels were measured by enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived a first AMI and 165 healthy women, matched by age and geographical origin. RESULTS: Using the 90th percentile of IgA anti-EPCR in the control group, IgA anti-EPCR were independently associated with AMI after adjustment for cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant increase in the risk was found when women above the 90th percentile were compared with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti-EPCR were similar in patients and controls. A total of 145 patients underwent coronary arteriography. IgA or IgM anti-EPCR were not different among patients with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24, respectively). CONCLUSIONS: High levels of IgA and, to a lesser extent, IgM anti-EPCR, are associated with AMI in young women.     

Association of increased fibrinogen concentration with impaired activation of anticoagulant protein C

BACKGROUND: Low levels of activated protein C (APC) are a risk factor for venous thrombosis. The mechanisms leading to interindividual differences in APC are not totally elucidated. Protein C is activated by the thrombin-thrombomodulin complex. As thrombin binds to fibrinogen and thrombomodulin through a common region, it is conceivable that fibrinogen influences the activation of protein C. This would help to explain the association between high levels of fibrinogen and an increased thrombotic risk. METHODS: We analyzed the association between circulating APC levels and fibrinogen concentration in 382 healthy subjects. Subsequently, we studied the effect of increasing fibrinogen concentrations on the APC generation on cultured endothelial cells. RESULTS: An independent inverse association between circulating APC levels and fibrinogen was found [betacoefficient, -0.16; 95% confidence interval (95% CI) -0.26, -0.06; P = 0.001]. For each 100 mg dL(-1) increase in fibrinogen, the independent risk of having low APC levels (<0.7 ng mL(-1)) was almost three times higher (OR 2.8; 95% CI 1.1, 7.2; P = 0.04). Accordingly, a notable association between increasing fibrinogen concentrations and the reduction in the thrombin-thrombomodulin dependent activation of protein C on endothelial cells was found (r = -0.57; P = 0.002). CONCLUSIONS: We present evidence of an inverse association between circulating APC and fibrinogen levels. According to this finding together with the results of our in vitro experiments, we propose that the impairment in the generation of APC on endothelial cells constitutes a new prothrombotic mechanism of fibrinogen.     

Circadian occurrence of variceal bleeding in patients with liver cirrhosis

Abstract  Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light-dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strategies.