The value of ripple mapping in the age of coherent mapping in scar-related atrial tachycardia.

BACKGROUND: An accurate display of scar-related atrial tachycardia (ATs) is a key determinant of ablation success. The efficacy of ripple mapping (RM) in identifying the mechanism and critical isthmus of scar-related ATs during coherent mapping is unknown. METHODS: A total of 97 patients with complex ATs who underwent radiofrequency catheter ablation at our center between October 2018 and September 2022 were included. ATs was mapped using a multielectrode mapping catheter on the CARTO3v7 CONFIDENCE module. Coherent and RM were used to identify the reentrant circuit. RESULTS: The mechanisms of 128 ATs were analyzed retrospectively (84 anatomic-reentrant ATs and 44 non-anatomic reentrant ATs). The median AT cycle length was 264 ± 25ms. The correct diagnosis was achieved in 83 ATs (68%) using only coherent mapping. Through coherent mapping plus RM, 114 ATs (84.2%) were correctly diagnosed (68% vs. 89%, p = .019). In non-anatomical reentrant ATs, 81% of the diagnostic rate was achieved by reviewing both coherent and ripple mapping compared to reviewing coherent mapping alone (81% vs. 52%, p = .03). Reviewing coherent mapping and ripple mapping showed a higher diagnostic rate in patients who underwent cardiac surgery than those with Coherent mapping alone (64% vs. 88%, p = .04). CONCLUSION: Coherent mapping combined with RM was superior to coherent mapping alone in identifying the mechanism of scar-related ATs post-cardiac surgery and non-anatomic reentrant ATs.

Sub-thermionic, ultra-high-gain organic transistors and circuits.

The development of organic thin-film transistors (OTFTs) with low power consumption and high gain will advance many flexible electronics. Here, by combining solution-processed monolayer organic crystal, ferroelectric HfZrOx gating and van der Waals fabrication, we realize flexible OTFTs that simultaneously deliver high transconductance and sub-60 mV/dec switching, under one-volt operating voltage. The overall optimization of transconductance, subthreshold swing and output resistance leads to transistor intrinsic gain and amplifier voltage gain over 5.3 × 104 and 1.1 × 104, respectively, which outperform existing technologies using organics, oxides and low-dimensional nanomaterials. We further demonstrate battery-powered, integrated wearable electrocardiogram (ECG) and pulse sensors that can amplify human physiological signal by 900 times with high fidelity. The sensors are capable of detecting weak ECG waves (undetectable even by clinical equipment) and diagnosing arrhythmia and atrial fibrillation. Our sub-thermionic OTFT is promising for battery/wireless powered yet performance demanding applications such as electronic skins and radio-frequency identification tags, among many others.

Ripple mapping-guided atrial tachycardia ablation following open-heart surgery.

Ripple mapping can make the visualization of activation conduction on a 3-dimensional voltage map and is useful tool for scar-related organized atrial tachycardia (AT). This study sought to assess the efficacy of ripple mapping for interpreting reentrant circuits and critical isthmus in postoperative ATs. 34 consecutive patients with a history of mitral valve surgery (mean age, 54.5 ± 12.4 years) underwent high density (HD) RM during ATs with CARTO3v4 CONFIDENSE system. The voltage activation threshold was determined by RM over a bipolar voltage map. The identification of underlying mechanisms and ablation setting was based on RM without reviewing activation mapping. A total of 41 ATs (35 spontaneous, 6 induced) were characterized. 39 reentry circuits were successfully mapped (cycle length, 256 ± 43 ms). Of the 41 ATs, 28 were confirmed by ripple mapping alone (68%), and 12 (29%) by ripple mapping and entrainment mapping. Of 12 ATs in the left atrium, 9 (75%) needed entrainment to confirm, compared with 5 (17.8%) in the right atrium. Primary endpoint after initial ablation set was achieved in 32 of the 34 patients (94.1%). Freedom from atrial arrhythmias was 79.4% after the follow-up of 12 ± 5 months. Of the seven patients with recurrence, three underwent the repeated catheter ablation. Ripple mapping precisely delineated reentrant circuits in post-cardiac surgery AT resulting in a high success rate of ablation. Entrainment maneuvers remain useful for elucidation of complex AT circuits.

Long-term and Temporal Outcomes of Transcatheter Versus Surgical Aortic-valve Replacement in Severe Aortic Stenosis: A Meta-analysis.

OBJECTIVE: To determine the 5-year and temporal performance of TAVR versus SAVR. BACKGROUND: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. METHODS: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. RESULTS: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03-1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79-1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14-1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. CONCLUSIONS: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted.

LBBAP in patients with normal intrinsic QRS duration: Electrical and mechanical characteristics.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an innovative pacing technology, which needs further study. METHODS: Seventy LBBAP patients with intrinsic QRS duration (QRSd) less than 120 ms were consecutively enrolled in our center. According to whether the left bundle branch potential (LBBp) was recorded or not, the patients were divided into the potential positive group (LBBAP+) and the potential negative group (LBBAP-). Electrocardiographic and echocardiographic parameters were used to evaluate electrical and mechanical characteristics. Lead parameters and complications were followed-up. RESULTS: There were 52 patients in LBBAP+ and 18 patients in LBBAP-. The QRSd and the left ventricular activation time (LVAT) were wider after LBBAP. QRSd showed no significant difference between LBBAP+ and LBBAP-. LVAT was significantly shorter in LBBAP+ than in LBBAP-. Frontal QRS axis shifted leftward and the V1 morphologies changed after LBBAP. QRS axis and V1 morphologies showed no significant differences between two groups. Paced R-wave transition moved forward compared with intrinsic R-wave transition in both groups. Peak systolic strain of left ventricle (LVPSS) increased, and peak systolic dispersion of left ventricle (LVPSD) did not change significantly after LBBAP. Systolic and diastolic function as well as mechanical synchronism had no significant differences between two groups. LBBAP had great pacing parameters. CONCLUSION: LBBAP changes electrical and mechanical characteristics and has good safety in patients with normal intrinsic QRSd. LBBAP+ and LBBAP- show no significant differences in mechanical synchronization and interventricular electrical synchronization. The LBBAP+ shows better left ventricular electrical synchronicity.

Next-generation sequencing identifies a novel heterozygous I229T mutation on LMNA associated with familial cardiac conduction disease.

LMNA gene encodes Lamin A and C (Lamin A/C), which are intermediate filament protein implicating in DNA replication and transcription. Mutations in LMNA are validated to cause cardiac conduction disease (CCD) and cardiomyopathy.In a Chinese family, we identified 5 members harboring the identical heterozygous LMNA (c.686T>C, I229T) disease-causing mutation, which was not found in the 535 healthy controls. In silico analysis, we revealed structural alteration in Lamin A/C I229T mutant. Furthermore, molecular docking identified human polycomb repressive complex 2 and Lamin A/C interact with higher affinity in the presence of I229T, thus may downregulate Nav1.5 channel expression.Our findings expanded the spectrum of mutations associated with CCD and were valuable in the genetic diagnosis and clinical screening for CCD. Molecular docking analysis provided useful information of increased binding affinity between mutant Lamin A/C and polycomb repressive complex 2. However, the concrete mechanism of LMNA mutation (I229T) remains undetermined in our study, future genetics and molecular studies are still needed.

Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing.

OBJECTIVES: The aim of this study was to assess the feasibility and efficacy of left bundle branch pacing (LBBP) using a novel intraseptal technique to deliver cardiac resynchronization therapy (CRT) in patients with left bundle branch block (LBBB) and nonischemic cardiomyopathy. BACKGROUND: His bundle pacing to correct LBBB is a viable alternative approach to achieve CRT but is limited by suboptimal lead delivery and high thresholds. METHODS: This was a prospective, multicenter study performed between June 2017 and August 2018 at 6 centers. Patients with nonischemic cardiomyopathy, complete LBBB, and left ventricular ejection fractions (LVEFs) ≤50% who had indications for CRT and/or ventricular pacing in whom LBBP was attempted were included. Success rates, QRS duration, LVEF, left ventricular end-systolic volume, and improvement in functional class were assessed. RESULTS: LBBP was successful in 61 of 63 patients (97%, mean age 68 ± 11 years, 52.4% men). During LBBP, QRS duration narrowed from 169 ± 16 to 118 ± 12 ms (p < 0.001). Pacing threshold and R-wave amplitude remained stable at 1-year follow-up compared with implantation values (0.5 ± 0.15 V/0.5 ms vs. 0.58 ± 0.14 V/0.5 ms and 11.1 ± 4.9 mV vs. 13.3 ± 5.3 mV, respectively). LVEF increased significantly (33 ± 8% vs. 55 ± 10%; p < 0.001), with a reduction in left ventricular end-systolic volume (123 ± 61 ml vs. 67 ± 39 ml; p < 0.001). LVEF had normalized (≥50%) in 75% of patients at 1 year. New York Heart Association functional class improved significantly from 2.8 ± 0.6 at baseline to 1.4 ± 0.6 at 1 year. No deaths or heart failure hospitalizations were observed during follow-up. CONCLUSIONS: LBBP is a feasible and effective method for achieving electric resynchronization of LBBB, with resultant improvements in left ventricular structure and function. Low and stable pacing thresholds may be advantageous over His bundle pacing for CRT in patients with LBBB and nonischemic cardiomyopathy.

Inhibition of RAGE by FPS-ZM1 alleviates renal injury in spontaneously hypertensive rats.

The current study was designed to examine the protection of RAGE-specific inhibitor FPS-ZM1 against renal injury in spontaneously hypertensive rats (SHR) and investigate the underlying mechanism. The adult male SHR were treated with FPS-ZM1 via oral gavages for 12 weeks, and age-matched male Wistar-Kyoto rats (WKY) were used as control. Treatment of SHR with FPS-ZM1 slightly reduced blood pressure, and significantly improved baroreflex sensitivity in SHR. Treatment of SHR with FPS-ZM1 improved renal function, evidenced by increased glomerular filtration rate and renal blood flow, and reduced plasma creatinine, blood urea nitrogen and urine albumin excretion rate. Histology results revealed that treatment of SHR with FPS-ZM1 alleviated renal injury and reduced tubulointerstitial fibrosis. Treatment of SHR with FPS-ZM1 suppressed activation of NF-κB and reduced expression of pro-inflammatory cytokines including Tnf, Il6, and Il1b. Treatment of SHR with FPS-ZM1 abated oxidative stress and downregulated mRNA levels of components of NADPH oxidase (Nox) including Cyba, Nox1, Nox2, Nox4 and Ncf1 in kidneys. In addition, treatment of SHR with FPS-ZM1 reduced renal AngII levels, downregulated mRNA expression of Ace and upregulated expression of Agtr2. In conclusion, treatment with FPS-ZM1 alleviated hypertension-related renal dysfunction, possibly by suppressing NF-κB-mediated inflammation, abating Nox-mediated oxidative stress, and improving local renal renin-angiotensin system (RAS).

PDK1-AKT signaling pathway regulates the expression and function of cardiac hyperpolarization-activated cyclic nucleotide-modulated channels.

AIM: The enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with cardiac and pathological remodeling and ion channel function regulation. However, whether it regulates hyperpolarization-activated cyclic nucleotide-modulated channels (HCNs) remains unclear. MAIN METHODS: In the atrial myocytes of heart-specific PDK1 "knockout" mouse model and neonatal mice, protein kinase B (AKT)-related inhibitors or agonists as well as knockdown or overexpression plasmids were used to study the relationship between PDK1 and HCNs. KEY FINDINGS: HCN1 expression and AKT phosphorylation at the Thr308 site were significantly decreased in atrial myocytes after PDK1 knockout or inhibition; in contrast, HCN2 and HCN4 levels were significantly increased. Also, a similar trend of HCNs expression has been observed in cultured atrial myocytes after PDK1 inhibition, as further demonstrated via immunofluorescence and patch-clamp experiments. Moreover, these results of PDK1 overexpression indicate an opposite trend compared with the previous experimental results. However, the results of PDK1 inhibition or overexpression could be reversed by activating or inhibiting AKT, respectively. SIGNIFICANCE: These results indicate that the PDK1-AKT signaling pathway is involved in the regulation of HCN mRNA transcription, protein expression, HCN current density, and cell membrane location.

Genetic Basis and Genotype-Phenotype Correlations in Han Chinese Patients with Idiopathic Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.

Meta-Analysis Comparing Results of Transcatheter Versus Surgical Aortic-Valve Replacement in Patients With Severe Aortic Stenosis.

Transcatheter aortic-valve replacement (TAVR) has emerged as a promising strategy for treating patients with severe aortic stenosis. We aimed to compare TAVR with surgical aortic-valve replacement (SAVR) and determine the performance of TAVR over time and within several subgroups. We included 8 randomized trials comparing TAVR versus SAVR. Compared with SAVR, TAVR was associated with a lower rate of all-cause mortality or disabling stroke at 30-day (odds ratio [OR], 0.72; p = 0.004), 1-year (OR, 0.83; p = 0.01), and 2-year (OR, 0.86; p = 0.02), but not at long-term follow-up (rate ratio [RR], 1.02 [confidence interval 0.92 to 1.13]; p = 0.67). Notably, 5-year data showed numerically higher incidence in TAVR (RR, 1.11 [confidence interval 0.97 to 1.27]; p = 0.12). The risks associated with TAVR versus SAVR increased over time, showing a significant interaction (p for interaction = 0.01), as were for new-onset atrial fibrillation and rehospitalization. Incidences of major bleeding, new-onset fibrillation, and acute kidney injury were lower in TAVR, whereas transient ischemic attack, major vascular complications, permanent pacemaker implantation, reintervention, and paravalvular leak were lower in SAVR. Incidences for all-cause and cardiovascular mortality, myocardial infarction, and stroke were not statistically different. TAVR with transfemoral approach and new-generation valve was associated with reduction in all-cause mortality or disabling stroke compared with corresponding comparators. In conclusion, TAVR was associated with a lower risk for all-cause mortality or disabling stroke within 2 years, but not at long-term follow-up compared with SAVR; the risks seems to increase over time. More data are needed to determine longer-term performance of TAVR.

Association Between Baseline, Achieved, and Reduction of CRP and Cardiovascular Outcomes After LDL Cholesterol Lowering with Statins or Ezetimibe: A Systematic Review and Meta-Analysis.

Background Several lipid-lowering therapies reduce CRP (C-reactive protein) independently of LDL-C (low-density lipoprotein cholesterol) reduction, but the association between CRP parameters and benefits from more-intensive LDL-C lowering is inconclusive. We aimed to determine whether the benefits of more- versus less-intensive LDL-C lowering on cardiovascular events related to baseline, achieved, or magnitude of reduction in CRP concentrations. Methods and Results PubMed, EMBASE, and Cochrane were searched through July 2, 2018. We included randomized controlled cardiovascular outcome trials of LDL-C lowering with statins or ezetimibe. Two reviewers independently extracted study data and rated study quality. Data were analyzed using meta-analysis and metaregression analysis. Rate ratios of mortality and cardiovascular outcomes associated with baseline, achieved, and magnitude reduction of CRP concentration were calculated. Twenty-four trials were included, with 171 250 patients randomly assigned to more- or less-intensive LDL-C-lowering treatments. Median follow-up duration was 4.2 years. More-intensive LDL-C lowering resulted in a significant reduction in incidences of all outcomes. Compared with less-intensive LDL-C lowering, more-intensive LDL-C lowering was associated with less reductions in myocardial infarction with a higher baseline CRP concentration (change in rate ratios per 1-mg/L increase in log-transformed CRP, 1.12 [95% CI, 1.04-1.22; P=0.007]), but not other outcomes. Similar risk reductions occurred for more- versus less-intensive LDL-C-lowering therapy regardless of the magnitude of CRP reduction or the achieved CRP level for all outcomes. Conclusions Baseline CRP concentrations might be associated with the benefits of LDL-C lowering on myocardial infarction, but no other outcomes, whereas the achieved and magnitude of reduction in CRP did not seem to have an important association.

Fever and neck pain after pacemaker lead extraction: A case report.

BACKGROUND: Venous thrombosis (VT) is one of the minor complications of pacemaker lead extraction. It is often found due to the swelling of the limbs after the extraction. It is easy to be neglected or even misdiagnosed in the absence of typical clinical symptoms. The incidence, risk factors, and long-term impact of this complication are still unclear. Herein, we report a case of deep VT caused by transvenous lead extraction, which is easily misdiagnosed. CASE SUMMARY: A 66-year-old woman underwent a pacemaker lead extraction at our hospital because of a pacemaker pocket infection. After the extraction, she began to experience intermittent fever accompanied by sweating. The highest body temperature recorded was 37.9 °C. Additionally, she reported migratory pain that made her uncomfortable. The pain was mistakenly thought to be caused by operation trauma. At first, the pain radiated from the left chest to the mandible. Then, the pain in the left chest was alleviated, but pain in the left neck and throat appeared. Finally, the pain was confined to the mandible and a submandibular mass was palpated with no other abnormalities upon physical examination. Computed tomography venography and angiography finally indicated that the fever and pain were the symptoms of thrombophlebitis caused by lead extraction. The patient was then treated with rivaroxaban for more than three months and has shown no symptoms since she left the hospital. CONCLUSION: The possibility of thrombosis should be considered when pain and recurrent fever occur after pacemaker lead extraction.

AMPK-mediated degradation of Nav1.5 through autophagy.

The voltage-gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down-regulated by AMPK-mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.-Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK-mediated degradation of Nav1.5 through autophagy.

Functional promoter -1816C>G variant of RANKL predicts risk and prognosis of lone atrial fibrillation.

Receptor activator of nuclear factor-κB ligand (RANKL) had been confirmed contributing to the development and progression of AF by regulating atrial structural remodeling. But the involved genetic mechanism is unknown. We intended to explore the association between the polymorphism RANKL -1816C>G (rs7984870) and susceptibility and prognosis of lone AF. RANKL rs7984870 was genotyped in a case-control study of 828 patients and 834 controls in Chinese population. The CG and/or CC genotypes had an increased lone AF risk [adjusted odds ratio (OR) 1.20 for CG, OR 2.16 for CC, and OR 1.55 for CG/CC], compared with the GG genotype. Moreover, patients carrying CG/CC genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying GG genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial RANKL expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CG and GG genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -1816 C/C allele than that of the -1816 G/G allele. These results suggested that RANKL rs7984870 is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of RANKL in AF.

Sex-specific mortality differences in heart failure patients with ischemia receiving cardiac resynchronization therapy.

BACKGROUND: Recent studies have reported prognosis differences between male and female heart failure patients following cardiac resynchronization therapy (CRT). However, the potential clinical factors that underpin these differences remain to be elucidated. METHODS: A meta-analysis was performed to investigate the factors that characterize sex-specific differences following CRT. This analysis involved searching the Medline (Pubmed source) and Embase databases in the period from January 1980 to September 2016. RESULTS: Fifty-eight studies involving 33445 patients (23.08% of whom were women) were analyzed as part of this study. Only patients receiving CRT with follow-up greater than six months were included in our analysis. Compared with males, females exhibited a reduction of 33% (hazard ratio, 0.67; 95% confidence interval, 0.62-0.73; P < 0.0001) and 42% (hazard ratio, 0.58; 95% confidence interval, 0.46-0.74; P = 0.003) in all-cause mortality and heart failure hospitalization or heart failure, respectively. Following a stratified analysis of all-cause mortality, we observed that ischemic causes (p = 0.03) were likely to account for most of the sex-specific differences in relation to CRT. CONCLUSION: These data suggest that women have a reduced risk of all-cause mortality and heart failure hospitalization or heart failure following CRT. Based on the results from the stratified analysis, we observed more optimal outcomes for females with ischemic heart disease. Thus, ischemia are likely to play a role in sex-related differences associated with CRT in heart failure patients. Further studies are required to determine other indications and the potential mechanisms that might be associated with sex-specific CRT outcomes.

Baseline serum globulin as a predictor of the recurrence of lone atrial fibrillation after radiofrequency catheter ablation.

OBJECTIVE: Inflammation and autoimmune responses play an important role in recurrence of atrial fibrillation (AF). Serum globulin levels are a commonly used clinical index that represents inflammation and autoimmune response. This study aimed to determine the relationship between baseline serum globulin levels and the risk of recurrence after ablation in lone AF patients. METHODS: We enrolled 348 lone AF patients undergoing radiofrequency catheter ablation for the first time for whom complete follow-up data were available. Pre-ablation peripheral venous blood samples were obtained for measurement of serum globulin levels. RESULTS: During the follow-up period of 22 months (range, 6-62), AF recurred in 129 patients (37.1%). Recurrence was associated with a low level of pre-ablation serum globulins. Multiple Cox proportional hazard regression analysis showed that persistent AF, AF duration, left atrial diameter, no amiodarone after ablation, and the serum globulin level in particular were independent predictors of AF recurrence. According to receiver operating characteristic curve analysis, the best diagnostic cut-off serum globulin level was 25.4 g/L, which showed 74.4% sensitivity, 71.3% specificity, and 73.3% accuracy. CONCLUSION: The baseline low serum globulin level is associated with AF recurrence after first-time ablation in lone AF patients. Therefore, it may be used as a predictor of AF recurrence in these patients.

A functional polymorphism C-509T in TGFß-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

Transforming growth factor-ß1 (TGF-ß1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-ß1 C-509 T polymorphism (rs1800469) was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR) = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-ß1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-ß1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509 T allele than that of the -509 C allele. In conclusion, the TGF-ß1 C-509 T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-ß1 in AF.

[Gene transfer of CD151 enhanced myocardial angiogenesis and improved cardiac function in rats with experimental myocardial infarction].

OBJECTIVE: To investigate the effects of in vivo CD151 gene transfer on angiogenesis and heart function in rats with myocardial infarction. METHODS: Acute myocardial infarction (AMI) was induced in male Sprague-Dawley (SD) rats by left anterior descending coronary artery ligation. The surviving rats randomly received myocardial injection of saline (MI control), pAAV-CD151 and pAAV-GFP (n = 12/group). Sham-operated rats without myocardial injection (n = 12) were taken as normal control. Four weeks later, heart function and the expression of CD151 were measured. Micro vessels density (MVD) in infarct myocardium was observed by factor VIII related antigen immunochemical staining. RESULTS: The expression of CD151 (1.98 +/- 0.23 vs. 0.91 +/- 0.09, P < 0.01) and MVD counting [(385.4 +/- 79.9) vs. (252.5 +/- 43.0) n/mm(2), P < 0.01] in pAAV-CD151 treated MI rats were significantly higher than that in MI control group, similarly, EF (64.0 +/- 8.7)% vs. (41.5 +/- 5.0)%, P < 0.01] and dp/dt(max) (6620.2 +/- 884.6 vs. 5545.5 +/- 693.0, P < 0.01) were also significantly increased post pAAV-CD151 treatment. These parameters were not affected by pAAV-GFP treatment. CONCLUSION: CD151 in vivo gene transfer for rats with acute myocardial infarction enhanced myocardial angiogenesis and improved left ventricular function.