Jingru Bao

Endocardial Autonomic Denervation of the Left Atrium to Treat Vasovagal Syncope An Early Experience in Humans

Background— Vasovagal syncope (VVS) is the most common cause of recurrent syncope that can be debilitating despite optimal conventional therapy. The aim of this study was to evaluate the feasibility and efficacy of selective endocardial autonomic denervation in left atrium (LA) as an alternative treatment strategy in patients with highly symptomatic VVS. Methods and Results— Ten consecutive patients (mean age, 50.4±6.4 years; 7 women) with a medium of 3.5 (range, 2–20) recurrent episodes of VVS during the preceding year and positive head-up tilt testing in whom standard therapies were ineffective or poorly tolerated were enrolled. Ganglionated plexi (GP) in the LA, identified by high-frequency stimulation, was targeted by radiofrequency catheter ablation. The patients were then followed up at 3, 6, 12, 24, and 36 months, including repeated head-up tilt testing and Holter at 3 and 12 months. Radiofrequency energy was applied at the left superior GP in 10 patients, right anterior GP in 5, and left inferior GP in 3, using an 8-mm ablation catheter. Vagal response, defined as transient ventricular asystole, atrioventricular block, or an increase in R-R interval by 50%, was observed during ablation in all GP sites. The end point of procedure was the inhibition of the vagal response at target sites. At 30±16 (range, 13–55) months of follow-up, no patient had any recurrence of syncope and all patients had significant improvement in symptoms, but 5 of 10 patients reported transient prodromes. No complications occurred. Conclusions— Comprehensive endocardial autonomic denervation of the LA demonstrates the feasibility of treating VVS in medium-term follow-up.

Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.

Background—Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics. Methods and Results—Ninety subjects diagnosed with ARVC who underwent electrophysiological study were recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations were identified in 57 (63%) subjects. Mutation carriers had more frequent clinical ventricular tachycardia (VT; 89% versus 55%; P<0.001) and negative T waves in V1 to V3 (61% versus 33%; P=0.016). Subjects with plakophilin-2 (PKP2) mutations also had more frequent VT than those without mutations in PKP2. Comparison between subjects with multiple and single mutations showed that syncope occurred more often in the former group (58% versus 24%; P=0.018). VT was significantly more often induced in mutation carriers compared with noncarriers (75% versus 39%; P=0.001), as well as in PKP2 mutation carriers compared with subjects without PKP2 mutations (80% versus 48%; P=0.002). Induced VT with a rate ≥200 bpm was more often documented in mutation carriers (88% versus 54%; P=0.013), as well as in PKP2 mutation carriers (91% versus 67%; P=0.041). Conclusions—Pathogenic gene mutations were found in nearly two thirds of subjects diagnosed with ARVC. Mutation carriers, especially PKP2, had a higher proportion of a history of VT and more inducible fast VT.

Clinical Profile and Prognostic Significance of Atrial Fibrillation in Hypertrophic Cardiomyopathy

Objectives: The clinical outcomes of hypertrophic cardiomyopathy (HCM) are largely unpredictable. This study aimed to investigate the relationship between atrial fibrillation (AF) and its prognostic implications in Chinese patients with HCM. Methods: From 1999 to 2011, 654 unrelated HCM patients were consecutively recruited at Fuwai Hospital. Medical history, including electrocardiographic and echocardiographic data, was analyzed. Results: AF was documented in 158 patients (24%). During follow-up of 4.2 ± 2.8 years, Kaplan-Meier analysis revealed that the presence of AF was associated with an increased risk for all-cause death (p = 0.001), cardiovascular death (p < 0.001), severe heart failure (p < 0.001) and ischemic stroke (p < 0.001). Multivariate analysis identified AF as an independent predictor of stroke-related death (HR 6.71, 95% CI 1.23-38.58, p = 0.03), advanced heart failure (HR 1.83, 95% CI 1.04-3.22, p = 0.04) and ischemic stroke (HR 9.98, 95% CI 4.06-24.53, p < 0.001). Furthermore, enlarged left atrial diameter was positively related to all-cause death (HR 1.09, 95% CI 1.05-1.13, p < 0.001), cardiovascular death (HR 1.08, 95% CI 1.04-1.20, p < 0.001) and development of advanced heart failure (HR 1.05, 95% CI 1.01-1.10, p = 0.01). Conclusions: AF predicts poor outcomes for patients with HCM. Left atrial dilation is also related to an adverse prognosis and provides additional prognostic information.

Female Sex Is Associated with Worse Prognosis in Patients with Hypertrophic Cardiomyopathy in China

Background Sex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM). Methods and Results A total of 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 to 2011. Compared to male patients, at baseline female patients were older at diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), and had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year follow-up period (range 2–7 years), survival analysis showed that the incidences of mortality from all causes, cardiovascular death and progression to chronic heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21–3.95, P = 0.010; HR 2.19, 95% CI 1.17–4.09, P = 0.014; HR 1.73, 95% CI 1.12–2.69, P = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was identified only in patients younger than 50 years old (P = 0.011, 0.011 and 0.009, respectively), but not for those 50 years or older. Conclusion Our results suggest that female sex is associated with worse survival and heart failure in HCM patients. Further studies are required to determine whether female hormones modify the clinical expression and prognosis of HCM.

The training and learning process of transseptal puncture using a modified technique

AIMS As the transseptal (TS) puncture has become an integral part of many types of cardiac interventional procedures, its technique that was initial reported for measurement of left atrial pressure in 1950s, continue to evolve. Our laboratory adopted a modified technique which uses only coronary sinus catheter as the landmark to accomplishing TS punctures under fluoroscopy. The aim of this study is prospectively to evaluate the training and learning process for TS puncture guided by this modified technique. METHODS AND RESULTS Guided by the training protocol, TS puncture was performed in 120 consecutive patients by three trainees without previous personal experience in TS catheterization and one experienced trainer as a controller. We analysed the following parameters: one puncture success rate, total procedure time, fluoroscopic time, and radiation dose. The learning curve was analysed using curve-fitting methodology. The first attempt at TS crossing was successful in 74 (82%), a second attempt was successful in 11 (12%), and 5 patients failed to puncture the interatrial septal finally. The average starting process time was 4.1 ± 0.8 min, and the estimated mean learning plateau was 1.2 ± 0.2 min. The estimated mean learning rate for process time was 25 ± 3 cases. Important aspects of learning curve can be estimated by fitting inverse curves for TS puncture. CONCLUSIONS The study demonstrated that this technique was a simple, safe, economic, and effective approach for learning of TS puncture. Base on the statistical analysis, approximately 29 TS punctures will be needed for trainee to pass the steepest area of learning curve.

Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy

BACKGROUND Cardiac remodeling is one of major pathological process in hypertrophic cardiomyopathy (HCM). Endothelin-1 has been linked to cardiac remodeling. Big endothelin-1 is the precursor of endothelin-1. METHODS A total of 245 patients with HCM were enrolled from 1999 to 2011 and partitioned to low, middle and high level groups according to their plasma big endothelin-1 levels. RESULTS At baseline, significant associations were found between high level of big endothelin-1 and left atrium size, heart function and atrial fibrillation. Big endothelin-1 was positively correlated with N-terminal B-type natriuretic peptide (r=0.291, p<0.001) and late gadolinium enhancement (LGE) on magnetic resonance imaging (r=0.222, p=0.016). During a follow-up of 3 (range, 2-5) years, big endothelin-1 level was positively associated with the risks of all-cause mortality, cardiovascular death and progression to NYHA class 3 or 4 (p=0.020, 0.044 and 0.032, respectively). The rate of above events in the highest tertile were 18.1%, 15.7%, 24.2%, respectively. After adjusting for multiple factors related to survival and cardiac function, the significance remained in the association of big endothelin-1 with the risk of all-cause mortality (hazard ratio (HR)=4.94, 95% confidence interval (CI) 1.07-22.88; p=0.041) and progression to NYHA class 3 or 4 (HR=4.10, 95%CI 1.32-12.75, p=0.015). CONCLUSION Our study showed that high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk.

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients.

Atrial involvement in arrhythmogenic right ventricular cardiomyopathy patients referred for ventricular arrhythmias ablation

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable myocardium disorder that predominantly affects the ventricle. Little is known about atrial involvement. This study aimed to assess atrial involvement, especially the role of genotype on atrium in ARVC.

Fast rate （≥ 250 beats/min） right ventricular burst stimulation is useful for ventricular tachycardia induction in arrhythmogenic right ventricular cardiomyopathy

Background One of the major challenges in arrhythmogenic right ventricular cardiomyopathy (ARVC) ablation is ventricular tachycardia (VT) non-inducibility. The study aimed to assess whether fast rate (≥ 250 beats/min) right ventricular burst stimulation was useful for VT induction in patients with ARVC. Methods Ninety-one consecutive ARVC patients with clinical sustained VT that underwent electrophysiological study were enrolled. The stimulation protocol was implemented at both right ventricular apex and outflow tract as follows: Step A, up to double extra-stimuli; Step B, incremental stimulation with low rate (< 250 beats/min); Step C, burst stimulation with fast rate (≥ 250 beats/min); Step D, repeated all steps above with intravenous infusion of isoproterenol. Results A total of 76 patients had inducible VT (83.5%), among which 49 were induced by Step C, 15 were induced by Step B, 8 and 4 by Step A and D, respectively. Clinical VTs were induced in 60 patients (65.9%). Only two spontaneously ceased ventricular fibrillations were induced by Step C. Multivariate analysis showed that a narrower baseline QRS duration under sinus rhythm was independently associated with VT non-inducibility (OR: 1.1; 95% CI: 1.0–1.1; P = 0.019). Conclusion Fast rate (≥ 250 beats/min) right ventricular burst stimulation provides a useful supplemental method for VT induction in ARVC patients.

Endocardial Autonomic Denervation of the Left Atrium to Treat Vasovagal SyncopeClinical Perspective: An Early Experience in Humans

Background— Vasovagal syncope (VVS) is the most common cause of recurrent syncope that can be debilitating despite optimal conventional therapy. The aim of this study was to evaluate the feasibility and efficacy of selective endocardial autonomic denervation in left atrium (LA) as an alternative treatment strategy in patients with highly symptomatic VVS. Methods and Results— Ten consecutive patients (mean age, 50.4±6.4 years; 7 women) with a medium of 3.5 (range, 2–20) recurrent episodes of VVS during the preceding year and positive head-up tilt testing in whom standard therapies were ineffective or poorly tolerated were enrolled. Ganglionated plexi (GP) in the LA, identified by high-frequency stimulation, was targeted by radiofrequency catheter ablation. The patients were then followed up at 3, 6, 12, 24, and 36 months, including repeated head-up tilt testing and Holter at 3 and 12 months. Radiofrequency energy was applied at the left superior GP in 10 patients, right anterior GP in 5, and left inferior GP in 3, using an 8-mm ablation catheter. Vagal response, defined as transient ventricular asystole, atrioventricular block, or an increase in R-R interval by 50%, was observed during ablation in all GP sites. The end point of procedure was the inhibition of the vagal response at target sites. At 30±16 (range, 13–55) months of follow-up, no patient had any recurrence of syncope and all patients had significant improvement in symptoms, but 5 of 10 patients reported transient prodromes. No complications occurred. Conclusions— Comprehensive endocardial autonomic denervation of the LA demonstrates the feasibility of treating VVS in medium-term follow-up.