Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, polymorphic VT, and ventricular fibrillation. Catecholaminergic polymorphic VT is caused by enhanced Ca2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial and endocardial optical mapping, chemical subendocardial ablation with Lugol's solution, and patch clamping in a knockin (RyR2/RyR2(R4496C)) mouse model to investigate the arrhythmogenic mechanisms in catecholaminergic polymorphic VT. In isolated hearts, spontaneous ventricular arrhythmias occurred in 54% of 13 RyR2/RyR2(R4496C) and in 9% of 11 wild-type (P=0.03) littermates perfused with Ca2+and isoproterenol; 66% of 12 RyR2/RyR2(R4496C) and 20% of 10 wild-type hearts perfused with caffeine and epinephrine showed arrhythmias (P=0.04). Epicardial mapping showed that monomorphic VT, bidirectional VT, and polymorphic VT manifested as concentric epicardial breakthrough patterns, suggesting a focal origin in the His-Purkinje networks of either or both ventricles. Monomorphic VT was clearly unifocal, whereas bidirectional VT was bifocal. Polymorphic VT was initially multifocal but eventually became reentrant and degenerated into ventricular fibrillation. Endocardial mapping confirmed the Purkinje fiber origin of the focal arrhythmias. Chemical ablation of the right ventricular endocardial cavity with Lugol's solution induced complete right bundle branch block and converted the bidirectional VT into monomorphic VT in 4 anesthetized RyR2/RyR2(R4496C) mice. Under current clamp, single Purkinje cells from RyR2/RyR2(R4496C) mouse hearts generated delayed afterdepolarization-induced triggered activity at lower frequencies and level of adrenergic stimulation than wild-type. Overall, the data demonstrate that the His-Purkinje system is an important source of focal arrhythmias in catecholaminergic polymorphic VT.     

Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR(R4496C)) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR(R4496C) mice (P=0.02). Twenty-one mice (8 WT, 8 RyR(R4496C), and 5 RyR(R4496C) pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR(R4496C) mice but none of the WT developed VT (P=0.02); 4/5 RyR(R4496C) mice pretreated with propranolol developed VT (P=0.56 nonsignificant versus RyR(R4496C) mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.     

Arrhythmogenic right ventricular dysplasia

Abstract A 23-year-old man presented with recurrent exercise-induced ventricular tachycardia (VT), complicated by systemic embolisation. Catecholamine - sensitive VT was reproduced on exercise testing and programmed electrical stimulation, displaying features suggestive of enhanced automaticity as well as re-entry. Both 2D-echocardiography and gated heart pool scan showed localised dyskinetic bulging in the right ventricle. A diagnosis of arrhythmogenic right ventricular dysplasia was made. This condition should be excluded in all young patients with otherwise unexplained ventricular arrhythmias. (Aust NZ J Med 1991; 21: 451–453.)     

Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulation; (2) decreased affinity of mutant RyR2 for FKBP12.6 causes CPVT; (3) K201 prevent arrhythmias by normalizing the FKBP12.6-RyR2 binding. We studied ventricular myocytes isolated from wild-type (WT) and knock-in mice harboring the R4496C mutation (RyR2(R4496C+/-)). Pacing protocols did not elicit delayed afterdepolarizations (DADs) (n=20) in WT but induced DADs in 21 of 33 (63%) RyR2(R4496C+/-) myocytes (P=0.001). Superfusion with isoproterenol (30 nmol/L) induced small DADs (45%) and no triggered activity in WT myocytes, whereas it elicited DADs in 87% and triggered activity in 60% of RyR2(R4496C+/-) myocytes (P=0.001). DADs and triggered activity were abolished by ryanodine (10 micromol/L) but not by K201 (1 micromol/L or 10 micromol/L). In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2(R4496C+/-) mice. Measurement of the FKBP12.6/RyR2 ratio in the heavy sarcoplasmic reticulum membrane showed normal RyR2-FKBP12.6 interaction both in WT and RyR2(R4496C+/-) either before and after treatment with caffeine and epinephrine. We suggest that (1) triggered activity is the likely arrhythmogenic mechanism of CPVT; (2) K201 fails to prevent DADs in RyR2(R4496C+/-) myocytes and ventricular arrhythmias in RyR2(R4496C+/-) mice; and (3) RyR2-FKBP12.6 interaction in RyR2(R4496C+/-) is identical to that of WT both before and after epinephrine and caffeine, thus suggesting that it is unlikely that the R4496C mutation interferes with the RyR2/FKBP12.6 complex.     

Nonischemic sustained ventricular tachycardia: clinical outcome in 12 patients with arrhythmogenic right ventricular dysplasia

The clinical course and long-term follow-up of 12 patients with arrhythmogenic right ventricular dysplasia causing ventricular tachycardia are presented. No patient had a history of congestive heart failure and the cardiothoracic ratio measured less than or equal to 0.5 in all patients. All 12 patients were symptomatic during ventricular tachycardia; syncope occurred in 4. Exercise-related symptoms were present in 8 (73%) of 11 patients. The mean right ventricular ejection fraction was 31% (range 20% to 54%), and the mean left ventricular ejection fraction was 68% (range 44% to 88%). Signal averaging of the rest electrocardiogram (ECG) revealed late potentials in five of eight patients. During programmed electrical stimulation, sustained or nonsustained ventricular tachycardia showing a left bundle branch block configuration was induced in all patients. One patient underwent right ventricular disconnection and died 1 week after operation of low cardiac output failure. The remaining 11 patients were all treated medically and are alive at a mean follow-up time of 7.9 years after the onset of symptoms. Recurrence of symptomatic and documented sustained monomorphic ventricular tachycardia occurred in eight patients and could not be predicted by results of long-term ECG monitoring, treadmill exercise testing or programmed stimulation. In conclusion, despite recurrence of ventricular tachycardia, patients with arrhythmogenic right ventricular dysplasia have a favorable outcome when treated medically. Noninvasive studies (imaging techniques, ambulatory ECG monitoring and exercise testing) provide data that may be sufficient in diagnosing arrhythmogenic right ventricular dysplasia.     

Treatment by endocavitary fulguration of recurrent ventricular tachycardia caused by right ventricular dysplasia

A 27 year old man had recurrent ventricular tachycardia since the age of 16. Different antiarrhythmic drugs were used successively without success (mexiletine, amiodarone, acebutolol, propafenone, sotalol). The diagnosis of VT due to arrhythmogenic right ventricular dysplasia was suggested by the morphology of the tachycardia (left-sided delay), surface ECG appearances (right bundle branch block and potential after the QRS in right precordial leads) and the presence of delayed potentials on right ventricular endocavitary recordings. However, there were no obvious RV changes on echo or angiographic examination. The arrhythmogenic zone was localised in the postero-basal zone of the RV using three electrophysiological criteria: the recording of delayed systolic potential in sinus rhythm which overlapped into diastole during tachycardia, mapping of ventricular depolarisation during VT and results of RV "pacemapping" reproducing the appearances of the spontaneous tachycardia. VT was reproducible on stress testing (non-sustained VT at the beginning of the recovery phase) and on endocavitary stimulation. One 250 joule electric discharge between the endocavitary electrodes and a large dorsal surface electrode prevented any further attacks without antiarrhythmic therapy (follow-up: one year). Control electrophysiological investigation after 4 months showed another potentially arrhythmogenic zone which is quiescent at present.     

Effects of oral flecainide treatment of refractory tachyarrhythmias

Oral flecainide treatment was given to five patients who were refractory to conventional antiarrhythmic agents. The five patients included one with atrioventricular reentrant tachycardia (AVRT), one with non-sustained ventricular tachycardia (nsVT) and three with sustained VT (sVT). Flecainide produced favorable responses in patients of AVRT, nsVT and sVT with arrhythmogenic right ventricular dysplasia (ARVD). In the case of AVRT, flecainide exhibited a preventive effect on tachycardia induced by programmed electrical stimulation (PES). In the case of nsVT, flecainide markedly reduced the number of VPC and abolished the VT on the Holter ECG. In the case of sVT with ARVD, sVT was not induced by PES after the flecainide. Long-term treatment with flecainide on these three cases produced complete prevention of tachycardias. As an adverse effect of flecainide, an aggravation of congestive heart failure was recognized in one case with cardiac sarcoidosis. PQ interval and QRS interval in all the cases were prolonged after flecainide. The results indicate that flecainide is a useful antiarrhythmic agent for tachyarrhythmias refractory to treatment with conventional drugs.     

Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (CASQ2). We engineered and characterized a homozygous CASQ2(R33Q/R33Q) mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2(R33Q/R33Q) mice develop bidirectional VT on exposure to environmental stress whereas CASQ2(R33Q/R33Q) myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2(R33Q/R33Q) hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2(R33Q/R33Q) CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.     

致心律失常性右室发育不良症的室性心动过速的低能量电消融治疗

本文报告4例致心律失常性右室发育不良患者,因为反复出现室性心动过速药物治疗无效,而经心内膜起搏标测,在右室心尖部(3例)与右室流出道(1例)找出室性心动过速起源灶,用70～100J直流电进行经导管电消融。术中无心包填塞及肺水肿等并发症。术后不再能诱发出临床型室性心动过速。随访半年,其中2例无心律失常出现,另2例分别在1周与3个月后复发。     

Influence of right ventricular site of stimulation and infarct location on the inducibility of ventricular tachycardia in patients with coronary artery disease

No prior studies have evaluated the relationship between the site of right ventricular stimulation, the site of prior infarction, and the inducibility of ventricular tachycardia (VT). This study was performed to determine if the location of pathologic Q waves influences the inducibility of VT at various right ventricular sites in patients with coronary artery disease (CAD) and a history of myocardial infarction (MI). In 30 patients with a history of sustained, monomorphic VT, CAD, prior MI, and pathologic Q waves, programmed ventricular stimulation was performed at the right ventricular apex, septum, and outflow tract, in random order. There was electrocardiographic evidence of an MI that was inferior in 11 patients, anterior in 10 patients, and both inferior and anterior in 9 patients. Sustained, monomorphic VT was induced in 27 of 30 patients (90%). There were no significant differences among the three sites in the rate of inducibility of VT. The rate of inducible VT at each of the three right ventricular sites was not affected by the location of prior infarction. In conclusion, among patients with sustained, monomorphic VT, CAD, and a history of MI, the incidence of inducible sustained, monomorphic VT is not influenced by the location of prior infarction, regardless of whether programmed ventricular stimulation is performed at the right ventricular apex, septum, or outflow tract.     

Unusual presentation of cardiac sarcoidosis

A 46-year-old white woman presented to the emergency department with hemodynamically stable sustained ventricular tachycardia (VT). She was chemically cardioverted with lidocaine. Her electrocardiogram, showing sinus rhythm, was unremarkable, and serial cardiac enzyme tests excluded myocardial infarction. A signal-averaged electrocardiogram was abnormal, with a filtered QRS duration of 187 milliseconds. Echocardiography showed normal left and right ventricular systolic function but revealed diastolic dysfunction of the left ventricle. Electrophysiologic testing revealed easily inducible sustained VT of 4 distinct morphologies. A diagnosis of possible arrhythmogenic right ventricular dysplasia was made based on the signal-averaged electrocardiographic and electrophysiologic findings. Cardiac magnetic resonance imaging showed no evidence of arrhythmogenic right ventricular dysplasia, however. An endomyocardial biopsy revealed noncaseating granulomas consistent with sarcoidosis. This case illustrates the importance of complete testing, including invasive studies such as endomyocardial biopsy, in patients presenting with life-threatening ventricular arrhythmias to establish a correct diagnosis.     

Role of electrophysiologic techniques in the selection of antiarrhythmic drug regimens for ventricular arrhythmias

Programmed electrical stimulation of the heart provides a useful new technique for guiding the selection of antiarrhythmic drug regimens in selected patients with ventricular tachycardia (VT) or ventricular fibrillation. The technique of programmed electrical stimulation has been applied successfully in patients with recurrent sustained VT, out-of-hospital ventricular fibrillation and unexplained syncope in the presence of structural heart disease. The complete suppression of VT induced by programmed electrical stimulation by a drug regimen is highly predictive of freedom from both recurrent VT and sudden death. In addition, this technique may hold promise as a means of assessing the arrhythmogenic effects of antiarrhythmic drugs in selected patients.     

Total disconnection of the right ventricular free wall: surgical treatment of right ventricular tachycardia associated with right ventricular dysplasia

Arrhythmogenic right ventricular dysplasia is a myopathy that affects the right ventricular free wall (RVFW) and gives rise to recurrent reentrant ventricular tachycardia (VT). Because the entire right ventricle is potentially arrhythmogenic, ablating a single site of VT may not eliminate the arrhythmia. We developed an operation to confine any arrhythmic activity arising from the right ventricle to that chamber: total disconnection of the RVFW from the left ventricle. We performed RVFW disconnection in two patients with refractory VT associated with arrhythmogenic right ventricular dysplasia. At least two sites or origin of morphologically distinct VT were identified in the RVFW in each patient. RVFW disconnection was carried out under normothermic cardiopulmonary bypass. An encircling incision was made along the attachment of the RVFW to the aortoventricular unit and the tricuspid annulus; the right coronary artery and its RVFW branches were left intact. Electrical activity of the two chambers became dissociated, and VT arising from the RVFW was confined to that chamber. Postoperatively, there was no clinical evidence of hemodynamic impairment (follow-up 4 months and 3 months). Left ventricular function was unchanged and right ventricular flow was maintained by atrial contraction and motion of the septum toward the RVFW during left ventricular systole. One patient had incessant right ventricular tachycardia confined to the RVFW for 3 weeks. We conclude that RVFW disconnection is feasible and applicable to patients with refractory VT originating in the diffusely diseased RVFW.     

Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes

Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction. RyR2 mutations suggested to cause defective Ca2+ channel function have recently been identified in catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia (ARVD) affected individuals. We report expression of three CPVT-linked human RyR2 (hRyR2) mutations (S2246L, N4104K, and R4497C) in HL-1 cardiomyocytes displaying correct targeting to the endoplasmic reticulum. N4104K also localized to the Golgi apparatus. Phenotypic characteristics including intracellular Ca2+ handling, proliferation, viability, RyR2:FKBP12.6 interaction, and beat rate in resting HL-1 cells expressing mutant hRyR2 were indistinguishable from wild-type (WT) hRyR2. However, Ca2+ release was augmented in cells expressing mutant hRyR2 after RyR activation (caffeine and 4-chloro-m-cresol) or beta-adrenergic stimulation (isoproterenol). RyR2:FKBP12.6 interaction remained intact after caffeine or 4-CMC activation, but was dramatically disrupted by isoproterenol or forskolin, an activator of adenylate cyclase. Isoproterenol and forskolin elevated cyclic-AMP to similar magnitudes in all cells and were associated with equivalent hyperphosphorylation of mutant and WT hRyR2. CPVT-linked mutations in hRyR2 did not alter resting cardiomyocyte phenotype but mediated augmented Ca2+ release on RyR-agonist or beta-AR stimulation. Furthermore, equivalent interaction between mutant and WT hRyR2 and FKBP12.6 was demonstrated.     

Clinical spectrum of ventricular tachycardia with left bundle branch morphology

Twenty-nine patients with apparent ventricular tachycardia (VT) of left bundle branch block (LBBB) morphology were evaluated. Tachycardia was associated with an organic basis in 24 of 29 patients: 7 had Mahaim fibers of the nodoventricular type, 7 had arrhythmogenic right ventricular dysplasia, 5 had coronary heart disease, 3 had biventricular cardiomyopathy, and 2 had associated congenital heart disease. In many patients the underlying cardiac disease was not readily apparent. In the patients with a Mahaim fiber, the electrocardiogram taken during sinus rhythm was frequently normal. A reentry tachycardia with anterograde conduction over the nodoventricular fiber could mimic VT as diagnosed by the usual criteria; nodoventricular fibers were, therefore, often unsuspected before electrophysiologic evaluation. In patients with arrhythmogenic right ventricular dysplasia, cineangiography demonstrated abnormalities of the right ventricle, but only minor or no abnormalities of the left ventricle. Clinical and electrocardiographic features were not distinctive. Of the 29 patients, 22 had serious symptoms accompanying the tachyarrhythmia or had required cardioversion. Patients were followed up for an average of 20 months: 4 patients died. Thus, VT exhibiting an LBBB morphology is not uncommon and is frequently associated with organic heart disease, serious symptoms, and significant mortality. Right ventricular angiography and electrophysiologic study may clarify the diagnosis in these patients.     

致心律失常性右室发育不良室性心动过速的电生理检查和外科治疗（附一例报告）

报告药物治疗无效、射频导管消融失败的致心律失常性右室发育不良（ＡＲＶＤ）顽固性室性心动过速（简称室速）１例患者，在电生理导引下行右室前游离壁隔离术治疗成功。术后随访７个月无室速发作，左室收缩功能正常。提示部分右室隔离术对有生命危险和药物治疗无效及射频导管消融失败的ＡＲＶＤ室速患者是安全、有效的     

Human cardiac ryanodine receptor mutations in ion channel disorders in Japan

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergic induced bidirectional or polymorphic ventricular tachycardias. Some of CPVT families were reported to be associated with cardiac ryanodine receptor gene (RyR2) mutations. However, association between RyR2 and other arrhythmogenic disorders is not clarified. In this study, we analyzed 83 Japanese patients including patients with long-QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, arrhythmogenic right ventricular cardiomyopathy and CPVT. Genetic screening of RyR2 revealed 3 distinct mutations among 4 families with CPVT (75% of incidence). However, no mutation was found in other groups. This is the first report to demonstrate prevalence of RyR2 mutations in various arrhythmogenic disorders in Japan. RyR2 mutations were detected frequently in CPVT but not in other diseases.     

Ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical presentation, risk stratification and results of long-term follow-up

BACKGROUND: Not all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are at risk for sudden cardiac death. The aim of the study was to evaluate the risk stratification in patients with ARVD/C. METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 34 ARVD/C patients. Twenty-two, 7 and 4 patients had documented sustained monomorphic ventricular tachycardia (smVT), non-smVT and ventricular fibrillation, respectively. One patient experienced syncope only. An implantable cardioverter defibrillator (ICD) was implanted in 11 patients inducible in smVT with hemodynamic compromise, in 4 patients with documented ventricular fibrillation and in one patient with non-smVT (194 ms tachycardia cycle length) (ICD group, n = 16). Ten patients were left without any antiarrhythmic therapy, 5 patients received antiarrhythmic drugs and 3 patients underwent successful VT ablation (non-ICD group, n = 18). Thirteen patients had an abnormal signal averaged ECG. During 6.5 +/- 2.4 years 69% of ICD patients received appropriate discharges and one non-ICD patient had a hemodynamically tolerated smVT recurrence (no sudden cardiac death in both groups). Comparison between the cycle lengths of clinical VT, induced VT and follow-up VT revealed a strong relationship (R = 0.62-0.88). On multivariate analysis abnormal signal averaged ECG and decreased left ventricular ejection fraction were statistically significant predictors for VT recurrence. CONCLUSIONS: In ARVD/C the tachycardia cycle length of clinical VT, PVS-induced VT and follow-up VT correlate well implicating that a PVS-guided approach does not provide additional information. Spontaneous arrhythmia in combination with clinical presentation allows identification of patients in need for an ICD.     

The Use of Fontaine Leads in the Diagnosis of Arrhythmogenic Right Ventricular Dysplasia

We report a case of a 68‐year‐old man admitted to the emergency department with syncope preceded by rapid palpitations. His admission ECG demonstrated a sustained ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). This report highlights the importance of distinguishing ventricular tachycardia caused by arrhythmogenic right ventricular dysplasia (ARVD) from the more benign idiopathic RVOT‐VT. Furthermore, we demonstrate the utility of the Fontaine leads placement in increasing the sensitivity for uncovering epsilon waves, a highly specific electrocardiographic feature that increases diagnostic accuracy in patients with ARVD.     

不同病因和不同类型室性心动过速心室晚电位检测

本文对63例不同病因和不同类型室性心动过速(简称室速)病人的晚电位(late potential,LP)检测结果表明,陈旧性心肌梗塞(OMI)伴单形持续性室速组LP检出率75％,与致心律失常性右室发育不良伴单形持续性室速组(100％)无显著性差异(P>0.05);而显著高于OMI伴非持续性室速组(31.5％,P<0.05)和特发性室速组(6.1％,P<0.001)。对不同组的部分病人进行了心脏电程序刺激,不同组的室速诱发率和诱发的刺激部位也不相同。本研究提示临床不同病因和不同类型室速的机制可能不同。