Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

The Effect of Accessory Pathway Location on Cardiac Function in Adult Patients with Wolff-Parkinson-White Syndrome.

INTRODUCTION: The relationship between ventricular pre-excitation and left ventricular dysfunction has been described in the absence of sustained supraventricular tachycardia in a series of case reports. However, there have been no systematic studies about the effect of ventricular pre-excitation on cardiac function in adult patients with different accessory pathway locations. METHODS AND RESULTS: Patients were divided into four groups based on the type and location of their accessory pathway: septal, right free wall, left free wall, and concealed. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, electrocardiogram recordings, electrophysiological properties, and transthoracic echocardiographic data (septal-to-posterior wall motion delay (SPWMD) and interventricular mechanical delay (IVMD) indicating intraventricular and interventricular dyssynchrony) were compared before and after successful ablation. Before radiofrequency catheter ablation, left ventricular ejection fraction (LVEF) was significantly lower in patients with septal and right free wall accessory pathways. Within three months after radiofrequency catheter ablation, NT-proBNP levels decreased, left ventricular function improved, and intraventricular left ventricular dyssynchrony disappeared. There was a negative correlation between initial LVEF with initial QRS duration and initial SPWMD. Notably, SPWMD had a stronger correlation with LVEF than initial QRS duration. CONCLUSIONS: Anterograde conduction with a septal or right free wall accessory pathway may cause left ventricular dyssynchrony and impair left ventricular function. Intraventricular left ventricular dyssynchrony seems to be responsible for the pathogenesis of left ventricular dysfunction. Radiofrequency catheter ablation results in decreased NT-proBNP levels, normalized QRS duration, mechanical resynchronization, and improved left ventricular function.

Electrophysiological manifestations of rare supra-ventricular tachycardias with concealed nodo-ventricular fibers.

PURPOSE: To clarify the electrophysiological mechanism of supra-ventricular tachycardias (SVT) with concealed nodo-ventricular (NV) fibers. METHODS: We studied the intra-cardiac electrograms during electrophysiological study (EPS) of three cases of SVT which concerned concealed NV fibers. Electrophysiological maneuvers including right ventricular apex entrainments, RS2 stimuli, adenosine triphosphate injection and so on were done for differential diagnosis before ablation. RESULTS: Among these patients, one had atrio-ventricular nodal reentrant tachycardia (AVNRT) with a bystander NV fiber; the other 2 had NV fiber mediated orthodromic reentrant tachycardias (NVRT). VA dissociation was observed during SVT in all 3 cases with an antegrade His bundle conduction sequence. Ventricular stimulation at His refractory period reset the H-H intervals and the V-V intervals sequentially, suggesting the existence of a retrogradely conductive accessory pathway. Adenosine injection could terminate these tachycardias. The cycle length of an NVRT prolonged during the status of functional right bundle branch block, suggesting that the fiber located on the right side. Multiple QRS fusion morphologies during ventricular entrainments or ventricular stimulation at His refractory period at a fixed position could be observed in these cases. CONCLUSIONS: Concealed NV fibers can either mediate orthodromic reentrant tachycardia or be a bystander of AVNRT. V-A dissociation usually occur during such SVTs. Dissociation of H and V due to entrainment of right ventricular apex is a newly discovered maneuver to differentiate AVNRT from NVRT.

The association of metabolic syndrome components and chronic kidney disease in patients with hypertension.

BACKGROUND: Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. METHODS: We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. RESULTS: A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28-2.57, p < 0.01), elevated fasting blood glucose (FBG) (OR = 1.43, 95% CI 1.00-2.07, p = 0.05) and hypertension grades (OR = 1.20, 95% CI 1.00-1.44, p = 0.05) were associated with the prevalence of CKD. In sub-group analysis, elevated TG remained strongly associated with CKD in both diabetes (OR = 2.10, 95%CI 1.22-3.61, p < 0.01) and non-diabetes (OR = 1.53, 95% CI 1.09-2.16, p = 0.01). In sub-group analysis of hypertension grades, there was also a graded trend between elevated TG and CKD from controlled blood pressure (BP) to hypertension grade 2 (OR = 1.81, 95%CI 1.06-3.11, p = 0.03; OR = 1.85, 95%CI 1.00-3.43, p = 0.05; OR = 2.81, 95% CI 1.09-7.28, p = 0.03, respectively). CONCLUSION: Elevated TG, elevated FBG and hypertension grades were significantly associated with the prevalence of CKD in patients with hypertension. Particularly, elevated TG was strongly associated with CKD, independent of diabetes and hypertension grades.

Recombinant leptin attenuates abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.

Vascular disease can manifest as stenotic plaques or ectatic aneurysms. Human abdominal aortic aneurysms (AAA) comprise an inflammatory disease characterized by the predominance of T helper type 2 (Th2) cytokine expression. Leptin has been clearly demonstrated to play an important role in regulating Th0 cell to Th1. So, we hypothesize that leptin has a protective effect on aneurysm formation. In this study, we demonstrated that intraperitoneal injection of leptin attenuated Ang II-induced AAA formation in ApoE-/- mice with no effect on serum lipids and systolic blood pressure. To investigate the mechanisms involved, we found that leptin pretreatment exhibited decreased protein expression of matrix metalloproteinase 2 (MMP-2) and MMP-9 and increased transforming growth factor-ß1 (TGF-ß1). We also examined potential mechanism of leptin as a modulator of the immune response. Our results proved that pretreatment with leptin downregulated protein expression of Th2 cytokine IL-4 and mRNA levels of GATA-3, the key transcription factor for Th2 polarization, and upregulated Th1 cytokine INF-γ and T-bet, the key transcription factor for Th1 polarization. Taken together, leptin, with the effect of regulation of Th1/Th2 cytokines, may have therapeutic potential for the treatment of AAA. Leptin may constitute a novel therapeutic strategy to prevent AAA formation.

PPAR-γ activation by rosiglitazone suppresses angiotensin II-mediated proliferation and phenotypictransition in cardiac fibroblasts via inhibition of activation of activator protein 1.

Cardiac fibroblasts play an important role in myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix proteins. Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands have been reported to have a number of cardioprotective properties. However, the mechanism underlying this protective effect has not yet been elucidated. The purpose of the present study was to investigate the effect of rosiglitazone on angiotensin II-induced cardiac fibroblast proliferation and differentiation. Cardiac fibroblasts were stimulated with angiotensin II (10(-7)M) in the presence or absence of rosiglitazone (10(-5)nM). Pretreatment of cardiac fibroblasts with rosiglitazone significantly inhibited angiotensin II-induced cardiac fibroblast proliferation and profibrotic phenotypes differentiation and, thus, reduced the overall production of collagen components. PPAR-γ antagonist GW9662 significantly inhibited these effects of rosiglitazone, suggesting that these effects of rosiglitazone were PPAR-γ-dependent. To investigate the mechanisms involved, we found that PPAR-γ activation by rosiglitazone inhibited the formation of c-fos/c-jun heterodimers and expression of activator protein 1 induced by ANG II and thus inhibited transcription of the downstream genes involved in CFs proliferation and differentiation. Our data suggests PPAR-γ activation could have an anti-fibrotic effect through limiting cardiac fibroblast proliferation and differentiation, which are the critical steps in the pathogenesis of cardiac fibrosis.