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Objective:To investigate the alteration of right ventricular function after catheter ablation in patients with persistent atrial fibrillation(PAF) and concomitant heart failure with preserved ejection fraction (HFpEF).Methods:The prospective observational study was performed in patients with HFpEF-PAF and undergoing first-time radiofrequency ablation procedures in the First Affiliated Hospital of Nanjing University between May to December 2019. Right ventricular functional parameters were measured before and 5 days, 1, 3, 6 and 12 months after the ablation by transthoracic echocardiography, respectively, including the right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion(TAPSE), tricuspid annular diameter (TVAD), tricuspid annular peak systolic speed(TDI-S′) and longitudinal strain of right ventricular free wall (RVFLS). Meanwhile, routine ECG and Holter recordings were performed at each follow-up time point.Results:In this study, atrial fibrillation (AF) recurrence occurred in 4 patients at the 3rd month after ablation, and 7 patients failed to follow up due to the Covid-19. Finally, 19 patients were followed up for the evaluation of cardiac function after catheter ablation. Compared with pre-ablation, right ventricular structural and functional paramters(RVFAC, TAPSE, TVAD, TDI-S′, RVFLS) improved significantly at all stages of follow-up( all P<0.05). Patients with atrial fibrillation recurrence had lower RVFLS and TDI-S′ at the baseline( P=0.039, P=0.019). Conclusions:Right ventricular function could improve in HFpEF-PAF patients who maintain sinus rhythm after radiofrequency ablation.
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Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.
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<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>
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Aged , Female , Humans , Male , Middle Aged , Atrial Appendage , Atrial Fibrillation , Atrial Flutter , Electrocardiography , Heart Atria , Ventricular Function, LeftABSTRACT
Objective To evaluate left ventricular(LV)myocardial contraction patterns and function when pacing in different right ventricular(RV)sites and discuss echocardiogarphic method to evaluate physiologcal pacing mode.Methods This study included 26 patients with paroxysmal supraventricular tachycardia without organic heart disease.Four pacing modes including right atrium pacing(AAI),RV apex pacing(VVI-RVA),RV septal pacing(VVI-IVS)and RV outflow tract pacing(VVI-RVOT)were performed on the patients in a random order after succussful radiofrequency ablation.The parameters measured in each pacing mode included(1)LV systolic function parameters:LV twist angle(Twist),aortic systolic velocity-time integral(VTIAo)and LV global strain(Gε)；(2)LV contracting pattern:segmental peak systolic strain(Sε),the time to peak value(TPε),and the distribution of segmental Sε,TPε in each layer or wall.The relationship between Sε,TPε of each wall was analyzed.[Results]Pacing from RV sites showed lower Twist,VTIAO and Gε than AAI mode.Gε demonstrated significant difference in three RV sites pacing mode(VVI-RVOT＞VVI-IVS＞VVI-RVA,P＜0.05).Compared with the AAI mode,the distribution of segmental Sε,TPε in the each layer or wall alerted significantly in three RV sites pacing mode,especially in VV1-RVA.The distribution pattern was similar in VVI-RVOT and VVI-IVS.Furthermore,the wall Sε collated negtively with wall TPε(r =-0.51,P＜0.001).[Conclusions]Compared with AAI mode,RV pacing,especially the VVI-RVA induced the alternation of LV contraction patterns and reduction of systolic function.Longitudinal strain parameters can be used to assess the myocardial contraction patterns and function in different pacing mode.
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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.
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Objective Previous investigations have shown that N-aeetylcysteine (NAC) could regulate diverse cell type's apoptosis. The purpose of this study was to evaluate the mechanism of NAC reversed apoptosis ofcardiomyocytes induced by hypoxia-reoxygenation (H/R). Methods Cardiomyocytes were treated with hypoxia 6 h and reoxygenation 72 h in the absence and presence of NAC (100 μmol/ L). The ROS was assayed by using Image-iTTM LIVE green reactive oxygen species detection kit. The viability of cell was assayed with trypan blue. Early stages ofapoptosis were assessed by flow cytometry using Annexin V, and late stages ofapoptosis were assessed using TUNEL system. Bcl2 and bax mRNA levels were determincd by real-time quantitative PCR. Bcl2, bax, p38 and pp38 protein levels were determined by western blot. Results We found that H/R could markedly increase ROS generation and induce the apoptosis of cardiomyocytes (P<0.01). NAC (100 p tool/L) significantly reduced the generation of ROS and apoptosis (P all <0.01). NAC also significantly reduced the protein ratio of pp38 and p38 and increased the RNA and protein ratio of bcl2 and bax (P all <0.01). Conclusion The results showed that NAC significantly reduced apoptosis through inhibiting the phosphorylation of p38 signal pathway, which has potential value for clinical cardiac diseases.
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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
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Objective To study the mode and clinical implications of onset of spontaneous tosade de pointes in the congenital long QT syndrome. Methods We reviewed electrocardiograms (ECGs) of 55 patients with congenital QT syndrome for syncope. Documentation of the onset of tosade de pointes was available for 16 patients. All these patients had "definitive long QT syndrome" by accepted clinical and ECG criteria. Results One hundren and forty-nine runs of tosade de pointes were documented in 16 patients,of whom,there were 130 runs of pause-dependent tosade de pointes. Conclusion Our results show that the pause-dependent tosade de pointes,which has been recognized as a hallmark of tosade de pointes in the acquired long QT syndrome,plays a major role in the genesis of tosade de pointes in the congenital long QT syndrome.
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<p><b>OBJECTIVE</b>To describe a new noncontact balloon catheter mapping system and to assess the clinical utility of this system for guiding endocardial mapping and ablation of tachycardia.</p><p><b>METHODS</b>Five patients with tachycardia underwent endocardial mapping and radiofrequency ablation using the noncontact balloon catheter mapping system. A 9 French, 64-electrode balloon catheter and a conventional 7 French electrode catheter for mapping and ablation were positioned in the same ventricular chamber. Ventricular three-dimensional geometry was established by the computerized mapping system. Using a boundary element inverse solution, 3360 virtual endocardial electrograms were computerized and used to derive isopotential maps. The earliest endocardial activation site, the exit site and the activation sequence of tachycardia or the critical isthmus of the reentry circuit were identified. Radiofrequency ablation with circular or linear lesion was performed at the target sites guided by the locator system.</p><p><b>RESULTS</b>Six clinical types of tachycardia, 5 of which were ventricular tachycardia and one was concealed fasciculoventricular fiber mediated tachycardia, were induced by programmed stimulation. The mean cycle length of these tachycardias was 336.6 +/- 42.69 msec. The earliest activation site and the exit site of 5 mapped tachycardias were all identified using the system. One type of ventricular tachycardia was hemodynamically unstable and difficult to terminate, and could not be mapped. Among the 6 types of tachycardias, radiofrequency ablation was successful in 4. There was no complication during and after the procedure. During the mean follow-up of 6 months, no tachycardia recurred in the patients with a successful ablation.</p><p><b>CONCLUSIONS</b>The noncontact mapping system described in this study has advantage over conventional mapping techniques for refractory tachycardia. It is not only helpful for understanding the electrophysiologic mechanism of a complex case, but also suitable for mapping hemodynamically intolerated and nonsustained ventricular tachycardia.</p>
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Adult , Humans , Male , Middle Aged , Body Surface Potential Mapping , Methods , Cardiac Catheterization , Catheter Ablation , Methods , Catheterization , Methods , Tachycardia, Ventricular , General SurgeryABSTRACT
Objective To describe the new cognition of mapping, ablation and mechanism of typical atrial flutter using non-contact mapping system. Methods In 9 patients with typital AFL, the bi-directional conduction properties of isthmus, atrial activation sequence and reentrant circuit of AFL were mapped using the non-contact mapping system. Linear isthmus radiofrequency ablation was guided by navigation system without fluoroscopy, and isthmus bi-directional block was verified. Results A clockwise moving reentrant activation wavefront in 1 of the 9 patients was observed and a counter-clockwise rotating wavefront in 7 of the 9 patients, respectively. AFL was not inducible in one patient. The mean cycle length of AFL was (215?36) ms. The whole reentrant way and its relation with anatomical structure of right atrium (RA) were displayed by non-contact mapping. In each mapped AFL, the wavefront conducted through the crista terminalis (CT) and propagated slowly, which that indicated the smooth part of RA was involved in the reentrant circuit. In patients with recurrences, the gap in the line of block in the isthmus was identified and ablated, which was navigated by the system. Complete isthmus bi-directional conduction block was achieved at the end of the procedure except in two patients. No recurrences of AFL occurred during the follow-up of 12-36 months. Conclusion The whole activation circuit and its relation with RA anatomical structure of typical AFL can be directly visualized and its reentry mechanism was verified by non-contact mapping system. In recurred cases ,the gap of isthmus block was identified and ablated accurately. CT, which was previously supposed to be a complete posterior conduction barrier, was now proved to be of transverse slow conduction by non-contact mapping.
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Objective To explore the mechanism of macro-reentry atrial tachycardia and to guide catheter ablation using electroanatomic mapping system in 3 patients.Methods Three patients(two females),aged 51?12 years,with atrial tachycardia were included.The mean history of symptom was 19?11 years.Conventional electrophysiological study was performed to determine the location of atrial tachycardia before the three dimensional geometry reconstruction.After voltage and activation maps were constructed,the mechanism of tachycardia was analyzed and the slow conduction areas(critical isthmus) were verified.Radiofrequency energy was delivered using irrigated-tip catheter.Results Though there was no evidence to suggest structural heart diseases,scar areas were found in the mapped atria in all the three cases.The mechanism of atrial tachycardia was found to be counter-clockwise macro-reentry around tricuspid valve,counter-clockwise macro-reentry around superior vena cava,and figure "8" reentry in left atria in the 3 patients respectively.The respective critical isthmus was found to be between the lateral scar and tricuspid valve,the lateral scar and superior vena cava,and two scars on the left atria roof.Ablation in the critical isthmus terminated all tachycardia.There were no atrial tachycardia recurrence during a follow-up of 9-10 months.Conclusion The substrate and electrophysiological mechanism of macro-reentry atrial tachycardia could be identified clearly,and navigation ablation could be performed effectively under the guidence of electroanatomic mapping.
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Objective To evaluate the effect of radiofrequency catheter ablation treament of supraventricular tachyarrhythmias on spontaneous attack of atrial fibrillation (AF) and to further discuss the electrophysiological mechanisms of AF. Methods Thirty-one patients (20 men, 11 women; mean age 54?12 years, age range 24-69 years) with supraventricular tachyarrhythmias coexisting with AF were included in the study. The mean history of the study group was 9?5 (range 1-19) years and the mean number of AF attack was 6?5 times (range 2-18). Of the 31 cases, 5 supraventricular tachyarrhythmias were electrophysiologically proven to be typical atrial flutter (AFL), 17 atrioventricular reentrant tachycardia (AVRT), 9 atrioventricular nodal reentrant tachycardia (AVNRT). Linear lesions to make bi-directional block were done in cavo-tricuspid isthmus in AFL patients, slow pathway modification in AVNRT and accessory pathway ablation in AVRT. Results After mean follow-up of 39?19 months (range 12-72), of the 31 patients, 23 had no occurrence of AF. In 3 of the 5 AFL patients, no AF occurred after ablation, but 2 still had AF occurrence, of whom one had frequent atrial premature contractions (APCs) and short runs of AF. In 26 patients with supraventricular tachycardia, 20 had no occurrence of AF after ablation. In the remaining 6, 2 had less frequent occurrence, and 4 remained the same, of whom one had hypertention with enlarged left atrium, and another had frequent APCs and short runs of atrial tachycardia. Conclusion AFL may share the same substrate with AF or may be the trigger factor of AF, and AVNRT and AVRT are only trigger factors of AF. So after successful ablation treatment of these tachycardias, no AF occurs. But in some cases, AF substrate still exists, and AF can be triggered by other trigger factors besides tachycardias mentioned above.