Xiang-Fei Feng

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

Abstract: Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), −0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, −8.67; 95% CI, −11.86 to −5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Association of the angiotensinogen M235T polymorphism with recurrence after catheter ablation of acquired atrial fibrillation

Purpose: Previous studies showed that genetic variants of the angiotensinogen (AGT) gene conferred higher risk for acquired atrial fibrillation (AF). The present study investigated whether AGT variants correlate with the clinical outcome in patients with acquired AF after catheter ablation (CA). Methods: A total of 150 acquired symptomatic drug-refractory AF patients (mean age 63.7±11.0 years, 24.6% non-paroxysmal AF) with acquired AF underwent a single CA procedure in our department and were included in this retrospective analysis. Eight tagging single nucleotide polymorphisms (tSNPs) in the AGT gene were genotyped. Standard electrocardiographs (ECGs) and 24-hour Holter recordings were performed during a median follow-up period of 57.5 months to detect AF recurrence. Results: Sixty-one patients (40.7%) suffered AF recurrences after a single CA procedure during follow up. Of the eight tSNPs, the frequency of the M allele of M235T was significantly higher in the recurrence group (28%) compared to the non-recurrence group (18%) (p=0.042). The recurrence rates of patients with the TT, MT, and MM genotypes were 34.4%, 50%, and 55.6%, respectively (ptrend=0.049). After adjusting for age, sex, body mass index, hypertension, left atrial volume index (LAVI) and other covariates, M235T increased the risk of AF recurrence in additive and dominant models with odds ratios of 2.023 (95% confidence interval (CI): 1.034–3.926, p=0.033) and 2.601 (95% CI: 1.102–6.056, p=0.025), respectively. However, in multiple correction analyses, the p values of multiple comparisons were not statistically significant (pcorrect>0.05). Conclusions: The M allele of M235T might be associated with an increased risk of AF recurrence after CA. Genotyping may thus be helpful on identifying patients with higher risks of AF recurrence after CA and developing optimal follow-up strategies. These strategies may differ and should be individualized according to patients’ genotype. Future studies are warranted to validate the potential effect of AGT M235T on AF recurrence post CA.

Value of Combining Left Atrial Diameter and Amino-terminal Pro-brain Natriuretic Peptide to the CHA2DS2-VASc Score for Predicting Stroke and Death in Patients with Sick Sinus Syndrome after Pacemaker Implantation

Background: The CHA2DS2-VASc score is used clinically for stroke risk stratification in patients with atrial fibrillation (AF). We sought to investigate whether the CHA2DS2-VASc score predicts stroke and death in Chinese patients with sick sinus syndrome (SSS) after pacemaker implantation and to evaluate whether the predictive power of the CHA2DS2-VASc score could be improved by combining it with left atrial diameter (LAD) and amino-terminal pro-brain natriuretic peptide (NT-proBNP). Methods: A total of 481 consecutive patients with SSS who underwent pacemaker implantation from January 2004 to December 2014 in our department were included. The CHA2DS2-VASc scores were retrospectively calculated according to the hospital medical records before pacemaker implantation. The outcome data (stroke and death) were collected by pacemaker follow-up visits and telephonic follow-up until December 31, 2015. Results: During 2151 person-years of follow-up, 46 patients (9.6%) suffered stroke and 52 (10.8%) died. The CHA2DS2-VASc score showed a significant association with the development of stroke (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.20–1.75, P < 0.001) and death (HR 1.45, 95% CI 1.22–1.71, P < 0.001). The combination of increased LAD and the CHA2DS2-VASc score improved the predictive power for stroke (C-stat 0.69, 95% CI 0.61–0.77 vs. C-stat 0.66, 95% CI 0.57–0.74, P = 0.013), and the combination of increased NT-proBNP and the CHA2DS2-VASc score improved the predictive power for death (C-stat 0.70, 95% CI 0.64–0.77 vs. C-stat 0.67, 95% CI 0.60–-0.75, P = 0.023). Conclusions: CHA2DS2-VASc score is valuable for predicting stroke and death risk in patients with SSS after pacemaker implantation. The addition of LAD and NT-proBNP to the CHA2DS2-VASc score improved its predictive power for stroke and death, respectively, in this patient cohort. Future prospective studies are warranted to validate the benefit of adding LAD and NT-proBNP to the CHA2DS2-VASc score for predicting stroke and death risk in non-AF populations.

Atrial Premature Contractions Arising from the Right Atrial Appendage

A 73‐year‐old man with a three months history of palpitations was referred for curative treatment of drug‐resistant frequent APCs or paroxysmal episodes of ATs in February 2017. The result of 24‐h Holter monitoring before admission showed that SV ectopics totaled 40,785, with 409 SV‐runs. Electrogram showed that the morphology of APC was negative in lead V1 and positive in the inferior leads [Figure 1]. Echocardiogram (ECG) data (left atrial [LA], 31.6 mm, left ventricular ejection fraction, 0.64), chest radiogram, and laboratory tests, including thyroid function, were all unremarkable.

Atrial Fibrillation Arising from the Left Atrial Appendage.

A 63-year-old patient presented for curative treatment of drug-resistant paroxysmal atrial fibrillation (AF). After pulmonary vein antrum isolation was achieved, AF could be still induced and persisted, while rapid activation at the left atrial appendage was conducted to the left atrium in a decremental conduction manner. A step-wise incremental discrete radiofrequency energy application at the ostium of left atrial appendage completely eliminated the AF. Neither AF nor atrial tachyarrhythmias reappeared, even under isoproterenol infusion and vigorous rapid atrial stimulations. The patient has experienced no symptoms or exhibited ECG evidence of AF during a 6-month follow-up.

Risk factors responsible for atrial fibrillation development between symptomatic patients with concealed or manifest atrioventricular accessory pathways

Background Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular accessory pathways (cAPs). However, the risk factors of developing AF in patients with various atrioventricular accessory pathways (APs) are not clear. Methods This retrospective study included 460 symptomatic patients with either cAPs (n = 246) or mAPs (n = 214) who underwent electrophysiological study and successful radiofrequency catheter ablation of APs. Clinical and electrophysiological characteristics were compared between cAPs and mAPs and between AF and non-AF groups with cAPs or mAPs. Independent risk factors of AF were analyzed using multivariate logistic regression. Results AF was more frequent in mAPs group than in cAPs group (23.4% vs 9.8%, p < 0.01). Clinical features were similar between cAPs and mAPs. Anterograde conduction properties served as the major electrophysiological feature of mAPs. Multivariate analysis indicated that mAPs, hypertension, post-ablation P wave dispersion (Pd), N-terminal proB-type natriuretic peptide (NT-proBNP) and creatinine were independent risk factors of AF in the complete cohort. Hypertension, post-ablation Pd and high-sensitivity C-reactive protein (hsCRP) were independent risk factors of AF in cAPs group. Post-ablation Pd, NT-proBNP, creatinine and shorter effective refractory period of anterograde accessory pathways (AAP ERP) were independent risk factors of AF in mAPs group. Conclusions Results from this study demonstrate that the risk factors of AF are not homogenous between concealed and manifest APs, which might suggest heterogeneous pathogenesis of AF in these two types of APs.

Non-response to Implantable Cardioverter Defibrillator in a Post-Infarction Patient with Recurrent Ventricular Tachycardia After Catheter Ablation

To the Editor: A 73-year-old man presented to Department of Cardiology at Xinhua Hospital, Shanghai Jiaotong University School of Medicine with a history of anterior wall myocardial infarction (MI) and multimorphic ventricular tachycardia (VT) in approximately September 2013. His VT burden became progressive increase despite treatment with percutaneous coronary intervention (PCI) and multiple antiarrhythmic medications such as beta blockers, amiodarone, magnesium sulfate, and so on. One month after PCI, the patient received an implantable cardioverter defibrillator (ICD) (Marquis, Medtronic, USA) implantation due to complex ventricular arrhythmias and depressed left ventricular ejection fraction (36%). The detection and therapy programming of the device included 2 zones: ventricular fibrillation (VF) zone (rate > 188 beats/min) and VT zone (rate 150–188 beats/min to VF zone). Later, the patient started to experience palpitations and shocks during physical activity. One month after the ICD implanted, the patient had to have the first radiofrequency catheter ablation (RFCA). Electroanatomic substrate mapping demonstrated a large area (53 cm2) of low amplitude electrograms (<0.5 mv) consistent with scar extending forward from the septum over to the lateral aspect of the heart [Figure 1]. Programmed stimulation induced two types of VT, VT1 (cycle-length (CL) 380 ms) “nonclinical” and the remaining VT2 (CL 430 ms) “clinical” as determined predominantly from the intracardiac electrogram morphology and CL analysis. A limited activation map demonstrated early activation at the apex and the lateral aspect of the scar, with a local electrogram preceding the onset of the QRS by approximately 70 ms. Entrainment mapping near these locations demonstrated concealed entrainment with a postpacing interval minus tachycardia CL of 15 ms. Ablation at these sites resulted in immediate VT termination. Figure 1 The electroanatomic map (right anterior oblique view) and ventricular tachycardia morphology. The top panel: electroanatomic map of the initial ablation procedure in a patient with recurrent ventricular tachycardia (VT). Brown tags indicated sites with ... Two weeks after the first RFCA, incessant, tolerated, slow (120–150 betas/min) VTs were detected by electrocardiogram monitoring, and these VTs were neither identified by ICD nor responded to multiple anti-arrhythmic medications. The ICD device was reprogrammed and new antitachycardia pacing (ATP) algorithms (VT zone: rate 130–188 beats/min) were performed, but this adjustment was failed and ended with shock therapy. To reduce the risk of receiving an inappropriate shock, the patient had a second RFCA treatment 1-month later. The area of second scarring had a larger scar (69 cm2) as assessed by electroanatomic mapping compared with the first, and the VT3 (CL 500 ms) critical isthmus was limited to the new region, which was “adjacent” to prior ablation lesions [Figure 1]. Radiofrequency lesions were placed at the new scar site and extended to the sites of late potentials in order to consolidate the lesions. Following ablation, VTs could no longer be induced. The procedure went well and there were no evidences of recurrent VTs and shock during 6 months postoperative follow-up. Several factors influence the termination of VT by ATP. The distance between the pacing site and the VT circuit may critically affect the ATP effectiveness.[1] Small changes in the VT CL were useful in predicting the ATP success.[2] In the present case, although an episode of VT had initiated, as the R-R intervals fluctuated beyond the detection threshold of ATP therapy, the device did not perceive these VT events, consequently ATP therapy was withheld. Little is known about the reason for recurrent VT after acutely “successful” catheter ablation.[3] Progressive fibrosis and remodeling may lead to the development of VT after the index event. Continued infarct remodeling may lead to the formation of new VT circuits that were not present during the initial ablation session.[3,4] In this case, the present patient had recurrent VTs that were resistant to treatment with antiarrhythmic drugs and ICD. The coexistence of three conditions is rare, and it is a challenge to treat. Some VTs failed to ATP therapy can lead to a delay in appropriate therapy, even contribute to a negative consequence. Thus, RFCA has become an important tool for the successful management of these VTs. It could result in the prevention of future VTs by ablating regions of slow conduction,[3] and all late potentials.[5] Hence, it is possible and effective for us to finish a linear pattern of lesions through sites of late potentials and good pace-maps.

Adenosine Sensitivity is Associated with Ablation Success Rate and Recurrence Rate with Nonirrigated Catheters in Patients with Ventricular Premature Contractions/Tachycardia from the Ventricular Outflow Tract

Background: A high ablation success rate for ventricular arrhythmia (VA) from outflow tract has been achieved, but some of them cannot be eliminated from endocardium. We investigated the association between adenosine sensitivity and ablation success/recurrence rates with a nonirrigated or an irrigated catheter. Methods: According to adenosine test, all patients were divided into a sensitive group (S group) or an insensitive group (I group). The patients of each group were randomized into a nonirrigated catheter (NA) subgroup or an irrigated catheter (IA) subgroup with a 2:1 ratio. Results: In S group of 122 patients (84 in NA subgroup), the ablation success rate was similar between two subgroups (94.7% vs. 90.5%, P > 0.05), but in I group of 94 patients (60 in NA subgroup), it was higher in IA subgroup (94.1%) than that in NA subgroup (73.3%, P < 0.05). The success rate using nonirrigated catheter was significantly higher in S group (90.5%) than that in I group (73.3%, P < 0.01), and the recurrence rate was lower in S group than that in I group (1.3%, vs. 13.6%, P < 0.05). On the contrary, the success rate and the recurrence rate using irrigated catheter were similar between S group and I group (94.7%, 94.1%, P > 0.05, vs. 2.8%, 6.3%, P > 0.05). Conclusions: Adenosine insensitivity is associated with a lower success rate and a higher recurrence rate for VA patients undergoing nonirrigated catheter ablation. Thus, irrigated catheters should be the first choice for VA ablation in adenosine insensitive patients.