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.

Efficacy of extended antrum ablation based on substrate mapping plus pulmonary vein isolation in the treatment of atrial fibrillation.

INTRODUCTION AND OBJECTIVES: Pulmonary vein isolation (PVI) technique has become the cornerstone of atrial fibrillation (AF) catheter ablation. The objective of this study was to assess the efficacy and safety of extended antrum ablation based on electrophysiological substrate mapping plus PVI in AF patients who underwent cryoballoon ablation. METHODS: In this observational study, a total of 121 paroxysmal AF patients and 80 persistent AF patients who did not achieve the procedure endpoint after cryoballoon ablation received extra extended antrum ablation (EAA) based on electrophysiological substrate mapping via radiofrequency ablation (EAA group). As a control group (PVI group), among paroxysmal AF and persistent AF patients, we conducted a propensity score-matched cohort, in whom only PVI was completed. RESULTS: The average follow-up time was 15.27±7.34 months. Compared with PVI group, paroxysmal AF patients in the EAA group had a significantly higher rate of AF-free survival (90.1% vs. 80.2%, p=0.027) and AF, atrial flutter, or atrial tachycardia (AFLAT) -free rate survival (89.3% vs. 79.3%, p=0.031). Persistent AF patients in the EAA group also had a significantly higher rate of AF-free survival (90.0% vs. 75.0%, p=0.016) and AFLAT-free survival (88.8% vs. 75.0%, p=0.029) than PVI group. Complication rates did not significantly differ between both groups, in either paroxysmal AF or persistent AF patients. CONCLUSION: Our findings demonstrate that extra extended antrum ablation based on electrophysiological substrate mapping is effective and safe. Moreover, the strategy can improve the outcome of AF cryoablation.

[Efficacy of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm post cardioverter-defibrillators implantation].

OBJECTIVE: To evaluate the acute and long-term effects of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm (VAS) post implantable cardioverter-defibrillators (ICD) implantation. METHODS: Acute and long-term effects of catheter radiofrequency ablation for the treatment of VAS post ICD implantation were retrospectively assessed in 11 patients from September 2008 to August 2011. RESULTS: A total of 15 ablation procedures were performed in 11 patients. Six ablation procedures were performed through epicardial approach. In 9 patients, 20 types of ventricular tachycardia (VT) (including 20% hemodynamically unstable VT) were induced during the procedures [mean cycle length (384 ± 141) ms] and polymorphic ventricular tachycardia were induced in 7 patients. The average X-ray fluoroscopy time and procedural time were (26 ± 17) min and (189 ± 60) min, respectively. Complete success, partial success, and failure rates immediately post catheter radiofrequency ablation were 46.7% (7/15), 26.7% (4/15) and 26.7% (4/15), respectively. All patients are alive at follow-up[(2.45 ± 9.6) months after the last catheter ablation] and the complete success, partial success, and failure rates during follow-up were 72.7% (8/11), 9.1% (1/11) and 18.2% (2/11), respectively. CONCLUSION: VAS can be effectively treated by catheter radiofrequency ablation in patients post ICD implantation.

[Effect of hepatocyte growth factor and transforming growth factor-ß(1) on atrial fibroblasts fibrosis].

OBJECTIVE: To investigate the effect of hepatocyte growth factor (HGF) and transforming growth factor-ß(1) (TGFß(1)) on the expression of α-smooth muscle actin (α-SMA) and collagen I in human atrial fibroblast in vitro, and to explore the possible molecular mechanism of atrial fibrosis in patients with atrial fibrillation (AF). METHODS: Human atrial fibroblast, isolated from aseptic right atrial appendage tissues of 10 sinus rhythm (SR) and 10 chronic atrial fibrillation (CAF) patients, were cultured with HGF and TGFß(1). mRNA expressions of collagen I and α-SMA were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), the protein expression of α-SMA was determined by immunofluorescence and Western blot. RESULTS: (1) Compared with SR group, left atrium was significantly dilated in CAF group (t = 2.692, P < 0.05), the mRNA expression of collagen I and α-SMA of atrial fibroblasts were significantly upregulated (all P < 0.01), mRNA expression of collagen I was positively correlated with left atrial dimension (LAD) (r = 0.836, P = 0.014), AF duration (r = 0.739, P = 0.045) and α-SMA mRNA level (r = 0.886, P = 0.012). (2) Compared with SR group, the expression of α-SMA protein in CAF atrial fibroblasts were significantly increased (P < 0.01). (3) TGFß(1) further stimulated while HGF significantly attenuated the expression of collagen I and α-SMA in CAF atrial fibroblasts (all P < 0.01). CONCLUSIONS: Increasing expression of collagen I and α-SMA in human atrial fibroblasts might promote atria remodeling leading to the development and sustaining of AF. HGF is involved in the negative regulation on the expression of α-SMA and collagen I.

[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.

[Effects of tetramethylpyrazine on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure induced by ventricular tachypacing].

OBJECTIVE: To explore the effects of tetramethylpyrazine (TMP) on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure (CHF) induced by ventricular tachypacing. METHODS: Twenty-one healthy mongrel dogs were randomly divided into three groups, which were normal control group, untreated group and TMP-treated group. Atrial fibrillation (AF) was induced by burst of atrial pacing, after the canine model of CHF was established. The atrial tissues were sampled and stained with Mallory's trichromic stains, then the fibrosis in the atrial tissues was analyzed. The left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The levels of angiotensin II (AngII), aldosterone (ALD), amino-terminal peptide of type III procollagen (PIIINP)ìlaminin (LN) and hyaluronic acid (HA) in peripheral blood were examined by radioimmunoassay. RESULTS: The LVEF was significantly decreased in the untreated group as compared with that in the normal control group (P<0.01), while the frequencies of AF and sustaining AF were significantly increased and the AF duration was obviously prolonged in the untreated group as compared with those in the normal control group (P<0.01). The fibrosis degree in the left or right atrial tissue in the untreated group was more serious than that in the normal control group (P<0.01). The AF duration was positively correlated with the fibrosis degree in the left atrial tissue (r=0.84, P=0.018). The levels of AngII, ALD, PIIINP and HA in peripheral blood were significantly higher in the untreated group than those in the normal control group (P<0.05 or P<0.01). The level of AngII was positively correlated with the level of ALD in peripheral blood (r=0.759, P=0.048). The LVEF and the frequency of sustaining AF were both significantly improved in the TMP-treated group as compared with those in the untreated group (P<0.05). The fibrosis in the left or right atrial tissue in the untreated group was more serious than that in the untreated group (P<0.01). The levels of AngII and PIIINP in peripheral blood were also markedly higher in the TMP-treated group than those in the untreated group (P=0.05, P=0.01). CONCLUSION: Tetramethylpyrazine has the effect of reducing the fibrosis degree of atrial tissue in dogs with CHF, and this efficacy may be related to the mechanism of decreasing the frequency of AF and shortening the AF duration.

[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.