范思洋
中国医学科学院阜外医院 心律失常中心
The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.
Journal of cardiovascular translational research 2023
BACKGROUND:Cardioneuroablation is an emerging therapy for refractory vasovagal syncope (VVS), but the standard enrollment criterion is undetermined. Mainstream studies empirically enroll patients with cardioinhibitory and mixed types of VVS on the basis of the head-up tilt (HUT). However, a variety of studies have shown that the results of HUT exhibit unpleasant reproducibility.OBJECTIVE:We aimed to investigate the prognostic value of baseline deceleration capacity in patients with refractory VVS after cardioneuroablation.METHODS:This study enrolled 123 patients (mean age 42.2±17.7 years; 54 males [43.9%]) with the diagnosis of VVS, of whom 16 patients had a negative result of HUT (13.0%), 8 (6.5%) had vasodepressive VVS, 32 (26.0%) cardioinhibitory VVS, and 67 (54.5%) mixed VVS. All patients underwent cardioneuroablation that was performed in the left atrium.RESULTS:After a mean follow-up of 4.0±1.1 years, 33 patients experienced syncope/presyncope events (26.8%). Patients with recurrent syncope/presyncope have a lower baseline deceleration capacity level than do those without (8.9±3.2 ms vs 11.3±3.7 ms; P < .001). Each 1-ms increase in deceleration capacity had a 34% (95% confidence interval [CI] 12%-50%) reduced risk of syncope/presyncope recurrence after cardioneuroablation. Nighttime deceleration capacity had the highest discrimination value (area under the curve 0.757; 95% confidence interval 0.657-0.858). At a high-risk threshold of 51% (nighttime deceleration capacity at a cutoff of 9.9 ms), the nighttime deceleration capacity enrollment strategy additionally benefited 18 per 100 patients after cardioneuroablation without syncope/presyncope recurrence as compared with the HUT strategy in decision curve analyses.CONCLUSION:Baseline nighttime deceleration capacity ≥ 10 ms may act as an indication for cardioneuroablation in patients with refractory VVS.
Heart rhythm 2022
Less is known about pregnancy in women with arrhythmogenic right ventricular cardiomyopathy (ARVC). From April 1995 to May 2018, 157 women with ARVC were retrospectively enrolled. Data on pregnancy and cardiac outcomes were analyzed. There were 224 pregnancies in 120 patients including 30 (13.4%) spontaneous and 2 (0.9%) medical abortions, 12 cardiac adverse events were recorded including new onset frequent premature ventricular contractions (PVC) in 3 (2.5%) patients, previous PVC numbers increased more than 100% in 5 (4.2%), syncope in 2 (1.7%), sustained ventricular tachycardia and heart failure required hospitalization each in one patient (0.8%). Women with cardiac events showed lower left ventricular ejection fraction (LVEF) (50.3 ± 2.7 vs 60.0 ± 7.3; p = 0.004). No significant change in cardiac structure and function was found at 1 year follow-up postpartum. At a median follow-up of 8 (1 to 32) years, 36 (22.9%) women died. Earlier symptom onset age (hazard ratio 1.046; 95% confidence interval 1.017 to 1.075; p = 0.002) and decreased LVEF (hazard ratio 1.127; 95% confidence interval 1.001 to 1.154; p = 0.041) increased the risk of all-cause mortality, pregnancy had no negative influence on survival. In all the 192 offsprings (mean age 26.3 ± 13.5 years), 2 died of sudden death, no definite ARVC was found. Pregnancy seemed to be acceptable in ARVC, decreased LVEF increased the risk of pregnancy and was associated with poorer long-term survival.
The American journal of cardiology 2020
AIMS:The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.METHODS AND RESULTS:Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Activation, entrainment, pace and substrate mapping strategies were used with regional ablation applied. A total of 393 ablation procedures were performed including endocardial approach only (n = 377) and endo and epicardial combined (n = 16). Right ventricular basal free wall was accounted as the primary substrate of VT in 258 (65.6%) patients. There were 81 patients underwent redo ablation procedure (second time = 81; ≥3 times = 28). New targets were observed in 68.8% of redo procedures. There were 171 VT recurrences and 19 deaths occurred during the follow-up. Ventricular tachycardia-free survival rate of the first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%, respectively. Multivariate analysis showed ≥3 induced VTs in the procedure was correlated with rehospitalized VT recurrence [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052-2.046; P = 0.024]. For all-cause mortality, rehospitalized VT and ≥3 induced VTs were the independent risk factors (HR 2.954, 95% CI 1.8068.038; P = 0.034; HR 3.189, 95% CI 1.073-9.482; P = 0.037).CONCLUSION:Endocardial ablation is effective to ARVC VT though it may require repeated procedures. Induced multiple VTs was correlated with worse outcomes.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2020
Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters. Nifekalant prolonged the shortest preexcited R-R, the average preexcited R-R, and the average R-R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with preexcited AF (all P<0.001). Nifekalant also decreased the percentage of preexcited QRS complexes, heart rate, and increased systolic pressure (all P<0.001). Nifekalant terminated AF in 33 of 51 patients (65%). Similar effects were also observed in a subgroup of 12 patients with preexcited AF and impaired left ventricular function. In patients with paroxysmal supraventricular tachycardia, nifekalant significantly prolonged the effective refractory period, the block cycle length of the antegrade accessory pathway, and the atrial effective refractory period (all P<0.001). Nifekalant had no effect on the effective refractory period of the antegrade atrioventricular node. Finally, in patients with persistent AF without an accessory pathway, nifekalant did not significantly decrease the ventricular rate of AF . One patient developed Torsades de Pointes. No other adverse effects were observed. Conclusions Nifekalant prolongs the effective refractory period of the antegrade accessory pathway and atrium without blocking antegrade conduction through the atrioventricular node, leading to slowing and/or to termination of preexcited AF . Thus, nifekalant might be an effective and a relatively safe drug in patients with preexcited AF .
Journal of the American Heart Association 2019
Less is known about bradyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). This cross-sectional study aimed to assess the prevalence and clinical significance of bradyarrhythmias in ARVC. From May 1995 to December 2017, bradyarrhythmias including sick sinus syndrome, atrioventricular block, and intraventricular conductional block (ICB) were investigated in 522 ARVC patients. A total of 169 patients (32.4%) presented with bradyarrhythmias including sick sinus syndrome in18 (3.5%), atrioventricular block in 56 (10.7%), and ICB in 118 patients (22.6%). Multivariate analysis showed right atrial dilation increased the risk of bradyarrhythmias (odds ratio [OR] 1.641, 95% confidence interval [CI] 1.081 to 2.492, p= 0.020). Bradyarrhythmias were not associated with death and heart transplantation. In patients with bradyarrhythmias, female gender, left atrial diameter >40 mm, and New York Heart Association Ⅲ/Ⅳ increased the risk of death and heart transplantation (hazards ratio [HR] = 2.790, 95% CI 1.220 to 6.377, p = 0.015; HR = 4.913, 95% CI 2.058 to 11.730, p <0.001; HR = 3.223, 95% CI 1.246 to 8.340, p = 0.016). Among the 23 patients who underwent device implantation, left atrial diameter >40mm was associated with death and heart transplantation (HR = 9.523, 95% CI 1.587 to 57.126, p = 0.014). In conclusion, bradyarrhythmias were commonly seen in ARVC, and ICB was the most common type. Female, left atrial diameter >40 mm, and NYHA class were associated with death and heart transplantation.
The American journal of cardiology 2019
Left atrial appendage (LAA) morphology is considered to be associated with ischemic stroke, non-Chicken Wing LAA morphology increases the risk of thromboembolic events. However, existing classification of LAA morphology remains not well quantifiable and therefore may leave room for substantial subjective interpretation. This study aimed to assess interobserver and intraobserver agreements in LAA morphology and its real value in stroke prediction. A total of 2,264 atrial fibrillation patients who underwent computed tomography to explore the LAA anatomy were enrolled. All computed tomography images were given to 3 reviewers to judge the LAA morphology independently. A consensus between all 3 reviewers was only reached in 655 cases (28.9%). In which, 86 patients had previous stroke. Poor intraobserver consistency was observed between 2 times of reading in all the 3 reviewers (Kappa = 0.368, p = 0.014; Kappa = 0.350, p = 0.014; Kappa = 0.333, p = 0.015). Multivariate analysis showed that persistent atrial fibrillation (odds ratio [OR] 1.679; 95% confidence interval [CI] 1.031 to 2.736; p = 0.037), female gender (OR 1.761; 95% CI 1.037 to 2.994; p = 0.036) and age (OR 1.029; 95% CI 1.004 to 1.056; p = 0.025) were associated with previous stroke. LAA morphology was not associated with previous stroke and non-Chicken Wing LAA morphology did not increase the risk of stroke (OR 1.392; 95% CI 0.847 to 2.288; p = 0.192). In conclusion, high interobserver and intraobserver variabilities suggested that existing classification of LAA morphology was unreliable, the interpretation of the relation between LAA morphology and stroke needs caution.
The American journal of cardiology 2019
BACKGROUND:The association between thyroid-stimulating-hormone (TSH) and prognosis of nonischemic dilated cardiomyopathy (NIDCM) in patients with normal thyroid function remains unclear.HYPOTHESIS:Our aim was to investigate the association between TSH and major adverse cardiovascular events in euthyroid NIDCM patients.METHODS:The original cohort consisted of 216 consecutive euthyroid NIDCM patients, with left ventricular ejection fraction (LVEF) ≤35%, who were observed from 2010 to 2013. Patients with persistent ventricular arrhythmia (VA) histories, amiodarone taken for VA prevention, or on heart transplant list within 1 year were excluded. A follow-up evaluation was performed, and VA events, heart failure (HF) exacerbation/heart transplant, cardiac death, or death from any cause were separately evaluated.RESULTS:A total of 184 patients were enrolled, and 97.8% (180/184) ultimately received follow-up evaluations. During the median 4.6-year follow-up, 24 VA events, 28 cardiac deaths, 30 all-cause deaths, 40 HF exacerbations, and 11 heart transplant events occurred. Serum TSH levels showed good predictive efficacies for VA events (area under the curve [AUC] = 0.702, 95% confidence interval [CI]: 0.629-0.767), and the risk of VA events increased, according to serum TSH quarters, as determined by Kaplan-Meier analysis (2.2% vs 13.4% vs 21.0% vs 30.0%, Q1-Q4, P = 0.011). Multivariable Cox analysis showed that patients at the Q4 level of serum TSH (>2.67 mIU/L) suffered an increased risk of VA events, compared with those at the Q1 level of TSH (hazard ratio [HR] = 15.88, 95% CI: 2.01-65.15) or those at the other three quarters (HR = 3.17, 95% CI: 1.38-7.26). However, the Q4 TSH level was not associated with other adverse cardiac events.CONCLUSION:An association between TSH levels and the risk of VA events may exist in euthyroid NIDCM patients.
Clinical cardiology 2019
BACKGROUND: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.METHODS:The incidence, characterization and predictors of atrial involvement were investigated. Nine known ARVC-causing genes were screened and the correlation between genotype and atrial involvement was assessed.RESULTS:Right atrium (RA) dilation, left atrium (LA) dilation, and sustained atrial tachyarrhythmias (ATa) were found in 45, 16 and 3 patients, respectively. Gene mutations were identified in 64 (64.0%) patients. Mutation carriers showed more RA dilation than noncarriers (54.7% vs. 27.8%, P = 0.009), and no difference in LA dilation and ATa. Multivariate analysis showed tricuspid regurgitation (OR: 18.867; 95% CI: 1.466-250.000; P = 0.024) increased the risk of RA dilation and decreased left ventricular ejection fraction (LVEF) (OR: 1.134; 95% CI: 1.002-1.272; P = 0.031) correlated with LA dilation, whereas genotype showed no significant effect. At a median follow-up time of 91 months, 7 patients died and 1 patient accepted heart transplantation. New-onset RA dilation, LA dilation, and sustained ATa were found in 8, 7, and 6 patients, respectively. Atrial involvement was not associated with the long-term survival. Despite mutation carriers showing more RA dilation, Kaplan-Meier analysis showed genotype was not associated with atrial involvement.CONCLUSION:Atrial involvement was common in ARVC. Tricuspid regurgitation and decreased LVEF increased the risk for atrial dilation. Genotype was not associated with atrial involvement.
Journal of cardiovascular electrophysiology 2018
