An evaluation of the clinical efficacy of the application of 28mm cryoballoon for linear ablation of left atrial apex combined with enlarged pulmonary vein vestibule ablation for persistent atrial fibrillation.

OBJECTIVE: to retrospectively investigate the efficacy and safety of the application of 28 mm cryoballoon for pulmonary vein electrical isolation (PVI) combined with top left atrial linear ablation and pulmonary vein vestibular expansion ablation for persistent atrial fibrillation. METHODS: From July 2016 to December 2020, 413 patients diagnosed with persistent atrial fibrillation were evaluated, including 230 (55.7%) in the PVI group (PVI only) and 183 (44.3%) in the PVIPLUS group (PVI plus ablation of the left atrial apex and pulmonary vein vestibule). The safety and efficacy of the two groups were retrospectively analyzed. RESULTS: The AF/AT/AFL-free survival rates at 6, 12, 18, 24 and 30 months after procedure was 86.6%, 72.6%, 70.0%, 61.1% and 56.3% in the PVI group and 94.5%, 87.0%, 84.1%, 75.0% and 67.9% in the PVIPLUS group, respectively. At 30 months after procedure, the AF/AT/AFL-free survival rate was significantly higher in the PVIPLUS group than in the PVI group (P = 0.036; HR:0.63; 95% CI:0.42 to 0.95). CONCLUSION: The application of 28-mm cryoballoon for pulmonary vein electrical isolation combined with linear ablation of the left atrial apex and expanded ablation of the pulmonary vein vestibule improves the outcome of persistent atrial fibrillation.

[Relationship between atrial fibroblast proliferation/fibrosis and atrial fibrillation in patients with rheumatic heart disease].

OBJECTIVE: To investigate the association between gene expressions of basic fibroblast growth factor (bFGF), smooth muscle alpha-actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) and atrial fibrosis in patients with atrial fibrillation (AF). METHODS: The right atrial tissue samples were taken from 75 patients with rheumatic heart disease underwent heart valve replacement surgery (34 patients with sinus rhythm, 11 patients with paroxysmal AF and 30 patients with persistent AF) and stained with picrosirius red for quantitative analysis of collagen accumulation. The mRNA and protein levels of bFGF, alpha-SMA and PCNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. RESULTS: The percent volume fraction of collagen (CVF) was the highest in persistent AF group and the lowest in the sinus rhythm group (all P < 0.01). CVF significantly correlated with AF duration (r = 0.390, P = 0.010) and left atria (LA) dimension (r = 0.320, P = 0.005). The mRNA and protein levels of bFGF, alpha-SMA and PCNA were significantly higher in the persistent AF group than those in the paroxysmal AF group (all P < 0.05) and significantly higher in both AF groups than those in the sinus rhythm group (P < 0.05-0.01). The mRNA and protein levels of bFGF were positively correlated with CVF (r = 0.330, P = 0.004 and r = 0.292, P = 0.013, respectively), AF duration (r = 0.330, P = 0.005 and r = 0.299, P = 0.010, respectively) and left atrial dimension (r = 0.342, P = 0.003 and r = 0.285, P = 0.015, respectively). CONCLUSION: The increased gene expressions of bFGF, alpha-SMA and PCNA in atrium during AF may contribute to atrial fibrosis by promoting fibroblast proliferation in AF patients.

[Collagen type I and interleukin-1 beta gene expression in human atria during atrial fibrillation].

OBJECTIVE: To determine whether gene expression of collagen type I and interleukin-1 beta (IL-1beta) is altered in patients with atrial fibrillation (AF). METHODS: Right atrial tissue samples were taken from 75 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF, 11 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I and IL-1beta was measured with semi-quantitative RT-PCR. RESULTS: The mRNA content of collagen type I was significantly increased in the persistent AF group (P < 0.001) and increased in the paroxysmal AF group (P < 0.05) as compared with that in the sinus rhythm group. The mRNA content of IL-1beta was up-regulated in the persistent AF group (P < 0.05), but the trend of increase did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA content of IL-1beta was significantly correlated with the mRNA content of collagen type I (r = 0.295, P = 0.011), left atrial dimension (r = 0.385, P = 0.001) and AF duration (r = 0.326, P = 0.004). CONCLUSION: The upregulation of IL-1beta gene expression in atrium may contribute to the atrial fibrosis during AF through influencing collagen metabolism.

[Changes in gelatinases expression and activity in human atria during atrial fibrillation].

OBJECTIVE: To determine whether expression and activity of atrial gelatinases are altered in patients with atrial fibrillation (AF). METHODS: The right atrial tissue samples were taken from 75 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients were in sinus rhythm, 11 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA and protein level of MMP-2, MMP-9, TIMP-1, TIMP-2 were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western-blotting analysis respectively. The activity of MMP-2 and MMP-9 was measured by zymographic analysis. RESULTS: (1) The mRNA level of MMP-2 increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group (P < 0.01, respectively). MMP-9 mRNA expression remained compatible within groups (P > 0.05). MMP-2 and MMP-9 protein expression was prominent in the persistent AF group compared with the sinus rhythm and paroxysmal AF groups (P < 0.01), the significant difference was also observed between the paroxysmal AF and sinus groups (P < 0.05). (2) TIMP-1 and TIMP-2 expression at mRNA and protein level were all down-regulated in the persistent AF group compared with the sinus rhythm group (P < 0.05), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05) except that of the mRNA level of TIMP-2 (P < 0.05). (3) The activity of MMP-2 and MMP-9 significantly increased in both paroxysmal AF and persistent AF groups compared with the sinus rhythm group (P < 0.05). The significant difference in MMP-9 was also observed between the persistent AF and paroxysmal AF groups (P < 0.01). (4) MMP-2 and MMP-9 expression at mRNA and protein level were positively correlated with left atrial dimension and AF duration (P < 0.05) and were negatively correlated with the mRNA and protein level of TIMP-2 and TIMP-1 respectively (P < 0.01). CONCLUSIONS: The upregulation of MMP-2,9 gene expression and activity, along with the selective downregulation of TIMP-1,2 may have contributed to the atrial structural remodeling during AF through influencing collagen metabolism.

[Clinical on molecular basis of atrial fibrosis in patients with atrial fibrillation investigation].

OBJECTIVE: To determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF. METHODS: The right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I, collagen type III, MMP-2, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to beta-actin or GAPDH. RESULTS: Compared to sinus rhythm group, the mRNA of collagen type I and MMP-2 increased significantly in the persistent AF group (all, P < 0.01), followed by the paroxysmal AF group (all, P < 0.05). The mRNA of collagen type III was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P > 0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all, P < 0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type I was significantly correlated with left atrial dimension (r = 0.336, P = 0.004) and AF duration (r = 0.339, P = 0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r = -0.326, P = 0.006), the mRNA of collagen type I (r = 0.322, P = 0.006), left atrial dimension (r = 0.300, P = 0.011) and AF duration (r = 0.300, P = 0.010). CONCLUSION: The increased level of collagen type I associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.