Clinical significance of the timing of early recurrence of atrial arrhythmia after pulmonary vein isolation: a two-institution clinical study.

Early recurrence of atrial arrhythmia (ERAA) after ablation frequently occurs, but there is limited evidence about ERAA-timing. This study aimed to investigate the association between ERAA-timing and late recurrence. We retrospectively investigated 332 patients who underwent PVI for paroxysmal atrial fibrillation at Nagoya University Hospital and Komaki City Hospital. Seventy-six patients (23%) had ERAA. The cutoff value of the first ERAA for late recurrence was set as 3 days, with a specificity of 77% and sensitivity of 43%. On multivariate analysis, first ERAA beyond 3 days (hazard ratio, 2.477; 95% confidence interval, 1.168-5.25; p = 0.018) and large left atrial diameter (LAD) (hazard ratio, 1.101; 95% confidence interval, 1.024-1.184; p = 0.009) were independent predictors for late recurrence. Patients who had first ERAA within 3 days and no ERAA beyond 3 days showed a significantly higher recurrence-free rate than those who had first ERAA beyond 3 days and those who had ERAA both within 3 days and beyond 3 days (89% versus 39%, 44%; p < 0.001). Moreover, the patients with ERAA within 3 days and LAD ≤ 37.7 mm showed a significantly higher recurrence-free rate than those with ERAA beyond 3 days and LAD > 37.7 mm, and as compared with the other patients (100% versus 26% and 60%, respectively; p < 0.001). ERAA beyond 3 days after ablation was a predictor for late recurrence. Among patients with ERAA, those with ERAA within 3 days and smaller LAD showed favorable prognosis after ablation.

Mechanisms with clinical implications for atrial fibrillation-associated remodeling: cathepsin K expression, regulation, and therapeutic target and biomarker.

BACKGROUND: The cysteine protease cathepsin K (CatK) has been implicated in the pathogenesis of cardiovascular disease. We sought to determine the link between atrial fibrillation (AF) and plasma CatK levels and to investigate the expression of and therapeutic target for CatK in vivo and in vitro. METHODS AND RESULTS: Plasma CatK and extracellular matrix protein peptides (intact procollagen type I of N-terminal propeptide; carboxyl-terminal telopeptide of type I collagen [ICTP]) were measured in 209 consecutive patients with AF (paroxysmal AF, 146; persistent AF, 63) and 112 control subjects. In addition, the regulation of CatK expression was investigated in vivo and vitro. Patients with AF had higher plasma CatK and ICTP levels than did control subjects. Patients with persistent AF had higher levels of plasma CatK and ICTP than did patients with paroxysmal AF. CatK was correlated with ICTP concentration and left atrial diameter in all subjects. In rabbits, superoxide production, CatK activity, fibrosis, and the levels of atrial tissue angiotensin II, angiotensin type 1 receptor, gp91phox, phospho-p38 mitogen-activated protein kinase, and CatK were greater in those with tachypacing-induced AF than in controls, and these changes were reversed with angiotensin type 1 receptor antagonist. Olmesartan and mitogen-activated protein kinase inhibitor decreased the CatK expression induced by angiotensin II in rat neonatal myocytes. CONCLUSIONS: These data indicated that increased plasma CatK levels are linked with the presence of AF. Angiotensin type 1 receptor antagonist appears to be effective in alleviating atrial fibrosis in a rabbit AF model, partly reducing angiotensin type 1 receptor-p38mitogen-activated protein kinase-dependent and -independent CatK activation, thus preventing AF.