Safety and Efficacy of Adenovirus Carrying Hepatocyte Growth Factor Gene by Percutaneous Endocardial Injection for Treating Post-infarct Heart Failure: A Phase IIa Clinical Trial.

OBJECTIVE: Our previous phase I clinical trial has confirmed the safety of Adenovirus carrying Hepatocyte Growth Factor gene (Ad-HGF) by intracoronary administration for treating severe coronary artery disease. This study was performed to evaluate the safety and efficacy of Ad-HGF by percutaneous endocardial injection for treating post-infarct heart failure. METHODS: A total of 30 patients (15 in the experimental group and 15 in the control group) with postinfarct heart failure who were not indicated to revascularization and had received the optimal standardized medication therapy were included in the study. Percutaneous endocardial Ad-HGF gene transfer was injected with a catheter-based intramyocardial delivery system in the experimental group. Safety parameters were measured and compared between baseline and follow-ups in the experimental group. The Mean Difference (MD) of efficacy parameters from baseline to 6-month follow-up was measured in both groups and compared with each other. RESULTS: No one suffered from serious adverse events in the experimental group during the 6-month follow-up. The experimental group revealed significant lower left ventricular end-diastolic dimension (LVDd) (68.5 vs. 65.8 MD: -2.69±1.08, P=0.03) and higher LVEF of both echocardiograph (35.2 vs. 39.3, MD: 4.05±0.86, P=0.0005) and single photon emission computed tomography (27.7 vs. 30.6, MD: 2.9±0.8, P=0.003) in the 6-month follow-up than that in the baseline, but the control group did not (P>0.05). Compared to the control group, the experimental group showed significant improvement ranges of lower LVDd (2.6 vs. -2.69, MD: -5.3±1.4, P=0.0009) and higher echocardiographic LVEF (-2 vs. 4.05, MD: 6.1±1.6, P=0.0008) from baseline to 6-month follow-up. CONCLUSION: Percutaneous endocardial administration of Ad-HGF is safe and potentially efficient in improving LVEF and lowering LVDd of patients with post-infarct heart failure.

Contribution of atrial activation to the segment of the typical atrial flutter wave: an electro-anatomic insight into the electrocardiogram morphology / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate how the intra-cardiac activation was translates into the characterized flutter wave in patients with cavatricuspid isthmus-dependent counter-clockwise atrial flutter (CTI-AFL).</p><p><b>METHODS</b>A total of 15 hospitalized CTI-AFL patients (mean age: (60 ± 14) years old, 1 female) from October 2012 to February 2014 were enrolled in the study. The activation map was re-constructed during AFL rhythm for left atrium and right atrium using 3-dimensional mapping system. The flutter wave in surface electrocardiogram was analyzed in combination with the intra-cardiac activation.</p><p><b>RESULTS</b>The mean left ventricular ejection fraction was (60.8 ± 6.6)%, and the left atrial diameter was (39.0 ± 3.4) mm. The mean tachycardia cycle length was (220 ± 24) ms. The activation map was completed in all cases. In inferior leads, the flutter wave was divided into three parts: slowly downward part, sharp downward part and the terminal positive part. The three parts corresponded to the fixed activation part of the macro-reentry.</p><p><b>CONCLUSION</b>The distinctive flutter wave of CTI-AFL was determined by the unique macro-reentry activation in the right atrium. The activation of left atrium contributes to the downward part of the wave.</p>

Reverse dedifferentiation of atrial cardiomyocytes after restoration of sinus rhythm from atrial fibrillation in goats / 老年心脏病学杂志（英文版）

Objective Chronic atrial fibrillation (AF) results in dedifferentiation of atrial cardiomyocytes that plays an important role in the perpetuation of AF.In this study,we aimed to investigate the changes of titin and α-smooth muscle actin (α-SMA) after long time of AF reversal.Methods Twenty-four goats were randomized into four groups:(1) sinus rhythm (SR),(2) 3 months AF (3-mo AF),(3) 3 months SR after 3 months AF (3-mo post AF),(4) 6 months SR after 3-mo AF (6-mo post AF),with 6 in each group.By pacing on the anterior bottom of left atria appendage (LAA),we established a goat model of chronic AF.Atria effective refractory period (AERP) was measured with electrophysiological methods.Ultra-structure was studied with echocardiography,light and electron microscopy.Titin and α-SMA protein expressions were determined by Western blot.Results The animals underwent high rate pacing on LAA for a mean of 42.23±21.70 days before presenting AF.Electrophysiological analysis revealed that AERP completely resumed in 3-mo post AF goats.Echocardiography displayed that the size of left atrium resumed almost in 6-mo post AF goats (P＜ 0.01).Pathological and electron microscopic examination revealed the disorder of myofibrils,augmentation of intercellular space,myolysis,accumulation of glycogen,and numerous bigger mitochondria among atrial cardiomyocytes in 3-mo AF goats.They recovered mostly in 6-mo post AF goats.Western blot showed that the band density of titin significantly reduced in 3-mo AF goats compared to SR ones [1826±319 vs 5012±854,P＜0.01].In 3-and 6-mo post AF goats,titin increased gradually and it reversed completely in 6-mo post AF goats (3841±601 and 4523±833 respectively,P ＜ 0.01).Conversely,the band density of α-SMA was significantly higher in 3-mo AF goats (5324±948) than in SR ones (1619± 271,P＜0.01).In 3-and 6-mo post-AF goats,α-SMA decreased gradually,and it recovered mostly in 6mo post AF goats (4437± 792 and 2205±540 respectively,P＜0.01,).Conclusions These data indicate that the reversal of dedifferentiation of atrial cardiomyocyts is a very slow process,and it is definitely essential for normal cardiac function.

Alterations of heart rate turbulence and immediate vagal reflex during left atrium circumferential pulmonary vein ablation / 中国介入心脏病学杂志

Objective To observe the alteration of heart rate turbulence(HRT) before and after left atrium circumferential ablation surrounding pulmonary veins(LACA) in patients with paroxysmal atrial fibrillation(PAF) in order to determine whether concealed vagal denervation occurred during the procedure.Methods Forty-four patients(26 male,aged 53?11 years) with paroxysmal atrial fibrillation who had received catheter ablation treatment from Mar 2006 to Dec 2006 were included in the study.The mean diameter of left atrium was 36?5 cm and the mean ejection fracion was 0.65?0.04 in these patients.The left atrium circumferential ablation surrounding pulmonary veins were performed in all the patients to achieve complete electrical isolation of both ipsilateral pulmonary veins.RS2 extrastimulus were delivered from right ventricular apex to obtain heart rate turbulence with 60% of basic sinus cycle length and at twice diastolic threshold before and after the procedure.Turbulence onset(TO)(%) and turbulence slope(TS)(msec/beat) were obtained using average five respective ventricular premature beats.Thirty-seven patients who had received catheter ablation of supraventricular tachycardia were included as control.Results There was no significant difference between AF and control group in HRT [TO:-0.021 6%?0.023 6% vs-0.023 6%?0.018 5%(P=0.67);TS: 7.331 8?6.983 5 vs 9.667 9?6.065 2(P=0.12)].TO and TS changed significantly after LACA [-0.021 6?0.023 6 to 0.000 9?0.013 3(P