Recurrences of Atrial Fibrillation Despite Durable Pulmonary Vein Isolation: The PARTY-PVI Study.

BACKGROUND: Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are mainly due to pulmonary vein reconnection. However, a growing number of patients have AF recurrences despite durable PVI. The optimal ablative strategy for these patients is unknown. We analyzed the impact of current ablation strategies in a large multicenter study. METHODS: Patients undergoing a redo ablation for AF and presenting durable PVI were included. The freedom from atrial arrhythmia after pulmonary vein-based, linear-based, electrogram-based, and trigger-based ablation strategies were compared. RESULTS: Between 2010 and 2020, 367 patients (67% men, 63±10 years, 44% paroxysmal) underwent a redo ablation for AF recurrences despite durable PVI at 39 centers. After durable PVI was confirmed, linear-based ablation was performed in 219 (60%) patients, electrogram-based ablation in 168 (45%) patients, trigger-based ablation in 101 (27%) patients, and pulmonary vein-based ablation in 56 (15%) patients. Seven patients (2%) did not undergo any additional ablation during the redo procedure. After 22±19 months of follow-up, 122 (33%) and 159 (43%) patients had a recurrence of atrial arrhythmia at 12 and 24 months, respectively. No significant difference in arrhythmia-free survival was observed between the different ablation strategies. Left atrial dilatation was the only independent factor associated with arrhythmia-free survival (HR, 1.59 [95% CI, 1.13-2.23]; P=0.006). CONCLUSIONS: In patients with recurrent AF despite durable PVI, no ablation strategy used alone or in combination during the redo procedure appears to be superior in improving arrhythmia-free survival. Left atrial size is a significant predictor of ablation outcome in this population.

Significance of membrane microparticles in solid graft and cellular transplantation.

Microparticles (MPs) are submicron vesicles released from stimulated or apoptotic cells after plasma membrane remodeling. In body fluids, they constitute relevant hallmarks of cell damage. Having long been considered inert debris reflecting cellular activation or damage, MPs are now considered as cellular effectors involved in cell-cell crosstalk. This review focuses on the pathophysiologic significance of MPs in the particular setting of solid graft and cellular transplantation.

Outcome of patients aged over 75 years who received a pacemaker to treat sinus node dysfunction.

BACKGROUND: The prognosis for patients aged over 75 years who receive a pacemaker in the context of sinus node dysfunction is unclear. AIMS: We sought to evaluate the incidences of atrial fibrillation, heart failure and death in such patients, and the role of the pacing mode in their prognosis. METHODS: This was a retrospective study of 102 patients aged over 75 years (mean 82.2 ± 4.4 years) who received a pacemaker in the context of sinus node dysfunction. RESULTS: During the follow-up period (mean 806 days), 36 patients (35.3%) experienced heart failure, 47 patients (46.1%) had an episode of paroxysmal atrial fibrillation, 19 patients (18.6%) progressed to chronic atrial fibrillation and 29 (28.4%) died, the fatal event being sudden death or of cardiac origin in almost half of these patients (44.8%). Patients assigned to dual-chamber minimal ventricular pacing showed significantly lower rates of heart failure episodes (P=0.023) and all-cause mortality (P<0.001) than those assigned to conventional dual-chamber pacing. In contrast, the two groups did not differ with regard to either paroxysmal or chronic atrial fibrillation. CONCLUSION: In patients aged over 75 years, the use of dual-chamber pacemakers incorporating an algorithm minimizing ventricular pacing for sinus node dysfunction seems to decrease the number of heart failure episodes and mortality. On the basis of this finding, the implantation of such devices seems justifiable, even in this age group.

Endothelial cell activation contributes to the release of procoagulant microparticles during acute cardiac allograft rejection.

BACKGROUND: Circulating procoagulant microparticles are reliable markers of vascular damage. The microparticle phenotypes provide additional information reflecting the nature of cell injury. This study assessed procoagulant microparticle levels and phenotypes in the diagnosis of acute allograft rejection after heart transplantation. METHODS: Microparticles were prospectively investigated in the venous blood of 64 heart transplant patients, 23 with allograft rejection mainly of low score, and 41 without a rejection episode. Plasma concentrations of cytokines, cytoadhesins, and platelet activation markers were determined. RESULTS: By univariate analysis, the mean time elapsed from heart transplant, cold ischemia time, E-selectin-, Fas- and tissue factor-bearing microparticles were associated with allograft rejection. By multivariate analysis, E-selectin-microparticle levels appeared independently associated with allograft rejection, even when other significant variables were included in the model (odds ratio, 9.8; 95% confidence interval, 1.36-71.4; p = 0.023). CONCLUSION: The pattern of procoagulant microparticles released during acute allograft rejection suggests endothelial cell activation and Fas-mediated apoptosis. E-selectin-bearing microparticles appeared as an independent marker of acute allograft rejection that was still informative after adjustment for graft characteristics.

Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.

RATIONALE: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors. OBJECTIVES: We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH). METHODS: Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined. MEASUREMENTS AND MAIN RESULTS: Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test. CONCLUSIONS: Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.

Procoagulant microparticles: disrupting the vascular homeostasis equation?

Apoptosis and vascular cell activation are main contributors to the release of procoagulant microparticles (MPs), deleterious partners in atherothrombosis. Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are associated with most of the cardiovascular risk factors and appear indicative of poor clinical outcome. In addition to being a valuable hallmark of vascular cell damage, MPs are at the crossroad of atherothrombosis processes by exerting direct effects on vascular or blood cells. Under pathological circumstances, circulating MPs would support cellular cross-talk leading to vascular inflammation and tissue remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant entities conveyed by circulating MPs. At sites of vascular injury, P-selectin exposure by activated endothelial cells or platelets leads to the rapid recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne TF, thereby triggering coagulation. Within the atherosclerotic plaque, sequestered MPs constitute the main reservoir of TF activity, promoting coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually harboring proteolytic and angiogenic effectors are additional actors in plaque vulnerability. Pharmacological strategies aimed at modulating the release of procoagulant MPs appear a promising therapeutic approach of both thrombotic processes and bleeding disorders.

Procoagulant microparticles: 'criminal partners' in atherothrombosis and deleterious cellular exchanges.

Procoagulant microparticles (MP) constitute valuable hallmarks of vascular cell damage at the crossroad of atherothrombosis processes. Detectable at low concentrations in the blood flow of healthy individuals, elevated levels of procoagulant microparticles are characteristic features of most cardiovascular risk factors. Circulating MP support cellular cross-talk leading to vascular inflammation, endothelial dysfunction, leukocyte adhesion and recruitment possibly contributing to plaque growth with consecutive development of local thrombosis and altered vasomotion. Within the plaque, MP shed by apoptotic monocytes and smooth muscle cells are major determinant of plaque thrombogenicity mainly through the presence of tissue factor (TF) activity. Besides this procoagulant potential, trapped MP could contribute to plaque vulnerability through multiple pathways including angiogenesis, extracellular matrix proteolysis, recruitment of inflammatory cells, smooth muscle cell and endothelial apoptosis. Having long been considered sufficient to initiate coagulation following plaque disruption, the role assigned to plaque-bound TF does not appear physically realistic at a macroscopic scale, the swift growth of the thrombus probably involving blood-borne TF conveyed by circulating MP. As participants in crucial steps of atherosclerotic disease, MP can now be viewed as "partners in crime" in acute ischemic syndromes.