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.     

Efficacy of flecainide in pacing-induced sustained ventricular tachyarrhythmias: correlation to clinical parameters and tachycardia-characteristics

Seventy-two patients with sustained ventricular tachycardiaor syncope of unknown origin underwent electrophysiologic evaluationbefore and after therapy with flecainide (200–300 mg day^–1).In all patients, sustained ventricular tachycardia or ventricularfibrillation was inducible during control electrophysiologicstudy. During flecainide therapy, sustained ventricular tachycardia(VT) was no longer inducible in 18 patients (25%) whereas in54 patients, VT was still inducible. In five of the latter patients,VT became more difficult to induce (overall efficacy 32%). Therate of VT decreased from 214±49 beats min^–1 duringthe control electrophysiologic study to 178±48 beatsmin^–1 during flecainide (P<0.01). The ERP of the rightventricle increased from 251±27 ms during the controlstudy to 267±34 ms on flecainide (P<0.01). Mean ejectionfraction and mean LVEDP did not differ between responders andnon-responders, yet the presence of a left ventricular aneurysmcorrelated with a lack of antiarrhythmic response to flecainide.VT rate as well as VT morphology during the control study discriminatedbetween responders and non-responders; 11% of patients withVT-rate 230 beats min^–1 responded to oral flecainidecompared with 31% with a VT rate > 230 beats min^–1at control. 26% with induced monomorphic VT responded, comparedwith 100% with induced VF during the control study. 18 of 23responders were discharged on flecainide. During a mean follow-upof 26±18 months, two patients experienced a recurrenceof VT and in one patient, flecainide had to be discontinueddue to side-effects. Thus, the acute efficacy of flecainide, evaluated by serialdrug testing, correlates with haemodynamic parameters and thecharacteristics of tachycardia.     

A missense mutation in the CASQ2 gene is associated with autosomal-recessive catecholamine-induced polymorphic ventricular tachycardia

Catecholamine-induced polymorphic ventricular tachycardia (CPVT), a rare disease that occurs in subjects without obvious organic heart disease, is characterized by episodes of syncope, seizures, or sudden death in response to physiologic or emotional stress. This report reviews evidence that a missense mutation in the CASQ2 gene is associated with autosomal-recessive CPVT.     

Electrocardiogram in Andersen-Tawil Syndrome. New Electrocardiographic Criteria for Diagnosis of Type-1 Andersen-Tawil Syndrome

Andersen - Tawil syndrome (ATS) is an autosomal - dominant or sporadic disorder characterized by ventricular arrhythmias, periodic paralysis, and distinctive facial and skeletal dysmorphism. Mutations in KCNJ2, which encodes the α-subunit of the potassium channel Kir2.1, were identified in patients with ATS. This genotype has been designated as type-1 ATS (ATS1). KCNJ2 mutations are detectable in up to 60 % of patients with ATS. Cardiac manifestations of ATS include frequent premature ventricular contractions (PVC), Q-U interval prolongation, prominent U-waves, and a special type of polymorphic ventricular tachycardia (PMVT) called bidirectional ventricular tachycardia (BiVT). The presence of frequent PVCs at rest are helpful in distinguishing ATS from typical catecholaminergic polymorphic ventricular tachycardia (CPVT). In typical CPVT, rapid PMVT and BiVT usually manifest during or after exercising. Additionally, CPVT or torsade de pointes in LQTS are faster, very symptomatic causing syncope or often deteriorate into VF resulting in sudden cardiac death. PVCs at rest are quite frequent in ATS1 patients, however, in LQTS patients, PVCs and asymptomatic VT are uncommon which also contributes to differentiating them. The article describes the new electrocardiographic criteria proposed for diagnosis of type-1 Andersen-Tawil syndrome. A differential diagnosis between Andersen-Tawil syndrome, the catecholamine polymorphic ventiruclar tachycardia and long QT syndrome is depicted. Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1.     

Respective role of sympathetic tone and of cardiac pauses in the genesis of 62 cases of ventricular fibrillation recorded during Holter monitoring

Sixty-two Holter recordings of sudden death due to ventricularfibrillation (VF) were analysed by full disclosure and computerizedprocessing. Thirteen sudden deaths were due to torsades de pointesin non coronary subjects (11/13), related to quinidine-likedrugs and/or hypokalaemia: they were always initiated by a longRR cycle due to a post-extrasystolic pause, and announced bya progressive decrease of mean heart rate (from 77.5 ±2.5 to 60.6 ± 2.7 beats min^–1, P<0.001), inthe three preceding hours. The other cases occurred in coronarypatients (45/49), with acceleration of ventricular tachycardia( VT), monomorphic in 24 cases, polymorphic in 13, the ventricularrate increasing from 220.6 ±55 to 241.5 ±69 beatsmin^–1, rather than with primary VF (12 cases). A cardiacpause (RR cycle exceeding 125% of the mean five preceding cycles)was present in 22/49 cases immediately before the onset of VT/VF.The coupling interval of the extrasystole initiating VT/ VFwas shorter than the shortest value encountered before: 377.6±± 94.5 ms vs 421.4 ± 92.3. The prematurityindex (coupling interval/preceding RR cycle ratio) was lowerin primary VF than in VT leading to VF. In the last hour precedingVF, ST changes were unusual (five cases), whereas heart rateincreased from82.8±20 to 92.0 ± 26.7 beats min^–1,(P<0001).This acceleration was in fact present only in caseswithout pauses before the onset of VT/VF: from 85.0±22.8to 99.1 + 31.1 (n = 27, P<0.001) whereas no changeoccurredin cases with preceding pause: from 79.8 ±15.5 to 80.8±16.3 (n = 22, P = NS). As a result, VT/VF without apreceding pause occurs in the setting of a higher heart rate,most probably reflecting a higher sympathetic drive. Preventionof these two main determinants by pacing and beta-blocking therapyshould bemore efficient than the use of antianginal or antiarrhythmicdrugs.     

Distinct U wave changes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT)

Although catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with fatal ventricular arrhythmias and sudden death, the ECG findings are not fully understood. In this paper, we report on alterations in the U-wave. Seven patients from 6 families with CPVT in which bidirectional tachycardia and polymorphic VT were induced by exercise or isoproterenol infusion visited our hospitals. VT was not inducible by programmed electrical stimulation. A novel gene mutation of the ryanodine receptor 2 (RyR2) was confirmed in 2 families. In one of these patients, U-wave alternans was observed following ventricular pacing at 160 beats/min. In the other patient, U-wave alternans was observed during the recovery phase after the exercise stress test, which was terminated because of polymorphic VT. In both cases, leads V3-V5 were the leads showing alternans most clearly. In the third patient, a negative U-wave became positive following a pause from sinus arrest and a change in T-wave was also noted. Since such findings were not found in the other subjects who underwent electrophysiologic study, isoproterenol infusion or exercise stress testing, the phenomenon seems to be relevant to the underlying pathogenesis of CPVT. The genesis and significance of U-wave alteration need to be determined.     

Mechanism underlying catecholaminergic polymorphic ventricular tachycardia and approaches to therapy

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. The diagnosis is made based on reproducible ventricular tachyarrhythmias including bidirectional VT and polymorphic VT during exercise testings. Two causative genes of CPVT have been identified: RYR2, encoding the cardiac ryanodine receptor (RyR2) Ca²⁺ release channel, and CASQ2, encoding cardiac calsequestrin. A mutation in RYR2 or CASQ2 is identified in approximately 60% of patients with CPVT. Mutations in these two genes destabilize the RyR2 Ca²⁺ release channel complex in sarcoplasmic reticulum and result in spontaneous Ca²⁺ release through RyR2 channels leading to delayed after depolarization, triggered activity, and bidirectional/polymorphic VT. Implantable cardioverter defibrillators (ICDs) are recommended for prevention of sudden death in patients with CPVT.1. A.E. Epstein, J.P. DiMarco, K.A. Ellenbogen, et al., ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008;117:e350 However, painful shocks can trigger further adrenergic stress and arrhythmias, and deaths have occurred despite appropriate ICD shocks. Treatment with β-adrenergic blockers reduces arrhythmia burden and mortality, but is not completely effective. The beneficial effects of Ca²⁺ channel blocker verapamil in combination with β-blocker have been reported, but the role of verapamil has not been well assessed. Because Ca²⁺ leakage through ryanodine channel is a common mechanism of CPVT, ryanodine channel block may have a therapeutic effect. We discovered that flecainide directly inhibits RyR2 channels and prevent CPVT. Left cardiac sympathetic denervation may be an effective alternative treatment in combination with ICD, especially for patients whose arrhythmias are not controlled by drug therapies.     

Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant form of arrhythmogenic disorder characterized by exercise- or emotional-induced polymorphic ventricular tachycardia in the absence of detectable structural heart disease. Because of the typical pattern of arrhythmias (bidirectional ventricular tachycardia and the occurrence and severity of arrhythmia correlated well with exercise workload) during exercise stress test, CPVT can be identified promptly. Molecular genetic screening of the genes encoding the cardiac ryanodine receptor and calsequestrin is critical to confirm uncertain diagnosis of CPVT. With the exception of beta-blockers, no pharmacologic therapy of proven effectiveness is available: although beta-blockers reduce the occurrence of ventricular tachycardia, 30% of patients treated with beta-blockers still experience cardiac arrhythmias and eventually require implantable cardioverter defibrillator implantation to prevent cardiac arrest.     

Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal form of inherited arrhythmogenic disease characterized by adrenergically mediated polymorphic ventricular tachycardia. The mutations in cardiac ryanodine receptor and calsequestrin genes are responsible for the autosomal dominant and recessive variants of CPVT, respectively. The clinical presentation encompasses exercise- or emotion-induced syncopal events and a distinctive pattern of reproducible, stress-related, bidirectional ventricular tachycardia in the absence of both structural heart disease and a prolonged QT interval. The mortality rate in untreated individuals is 30-50% by age 40. Clinical evaluation by exercise stress testing and holter monitoring and genetic screening can facilitate early diagnosis. beta-adrenergic blockers are the most effective pharmacological treatment in controlling arrhythmias in CPVT patients, yet about 30% of patients still experience cardiac arrhythmias and eventually require an implantable cardioverter defibrillator.     

Ventricular tachycardia in myocardial infarction: Relation to heart rate and premature ventricular contractions

Analysis of monitored electrocardiograms, recorded in 77 patientsduring the first 48 hours following the onset of myocardialinfarction, revealed 492 episodes of ventricular tachycardiawith rates of 90–220 min^–1. Characteristics of theventricular tachycardia episodes were correlated with heartrate and with the rate and complexity of ventricular arrhythmiasin the 10-min period preceding ventricular tachycardia. Ventriculartachycardia with rates of 140–180 min^–1 and witha QS configuration was the most frequent event. The first ectopiccomplex of VT was R-on-Tin only 17.2%. Sinus tachycardia wasassociated with significantly fewer episodes of VT with ratesof 110–140min^–1 than when the sinus rate was normal.However episodes of ventricular tachycardia with rates of 181to 220 beats min^–1 were more frequent during sinus tachycardia.Analysis of the frequency of premature ventricular contractionsin the 10-min period immediately preceding ventricular tachycardiarevealed no premature ventricular contractions in 24.4% of cases.Multiple premature ventricular contractions with a frequencyof >5 min^-1 were observed in 8.4% of cases, multifocal in30.3%, couplets in 24% and early PVCs in 12.2%. In the minutebefore ventricular tachycardia, only 40.2% of cases displayedpremature ventricular contractions. In that minute, complexpremature ventricular contractions were distributed as follows:multifocal in 10%, couplets in 8.7% and early PVCs in 2.6% ofcases. Out of the total of 492 runs of ventricular tachycardia,5 cases (1%) resulted in ventricular fibrillation. The frequencyand complexity of premature ventricular contractions as wellas the characteristics of ventricular tachycardia were foundto be of little predictive value for the immediate developmentof ventricular fibrillation in patients with acute myocardialinfarction.     

Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing

BACKGROUND: Mutations in the RyR2-encoded cardiac ryanodine receptor/calcium release channel and in CASQ2-encoded calsequestrin cause catecholaminergic polymorphic ventricular tachycardia (CPVT1 and CPVT2, respectively). OBJECTIVES: The purpose of this study was to evaluate the extent of genotypic and phenotypic heterogeneity among referrals for CPVT genetic testing. METHODS: Using denaturing high-performance liquid chromatography and DNA sequencing, mutational analysis of 23 RyR2 exons previously implicated in CPVT1, comprehensive analysis of all translated exons in CASQ2 (CPVT2), KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), KCNE2 (LQT6), and KCNJ2 (Andersen-Tawil syndrome [ATS1], also annotated LQT7), and analysis of 10 ANK2 exons implicated in LQT4 were performed on genomic DNA from 11 unrelated patients (8 females) referred to Mayo Clinic's Sudden Death Genomics Laboratory explicitly for CPVT genetic testing. RESULTS: Overall, putative disease causing mutations were identified in 8 patients (72%). Only 4 patients (3 males) hosted CPVT1-associated RyR2 mutations: P164S, V186M, S3938R, and T4196A. Interestingly, 4 females instead possessed either ATS1- or LQT5-associated mutations. Mutations were absent in >400 reference alleles. CONCLUSION: Putative CPVT1-causing mutations in RyR2 were seen in <40% of unrelated patients referred with a diagnosis of CPVT and preferentially in males. Phenotypic mimicry is evident with the identification of ATS1- and LQT5-associated mutations in females displaying a normal QT interval and exercise-induced bidirectional VT, suggesting that observed exercise-induced polymorphic VT in patients may reflect disorders other than CPVT. Clinical consideration for either Andersen-Tawil syndrome or long QT syndrome and appropriate genetic testing may be warranted for individuals with RyR2 mutation-negative CPVT, particularly females.     

Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia

BACKGROUND: The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade. OBJECTIVE: The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload. METHODS: Five patients with CPVT and one with polymorphic VT (PVT) and hypertrophic cardiomyopathy who had exercise-induced ventricular ectopy despite beta-blocker therapy were studied. Symptom-limited exercise was first performed during maximal beta-blocker therapy and repeated after addition of oral verapamil. RESULTS: When comparing exercise during beta-blockers with exercise during beta-blockers + verapamil, exercise-induced arrhythmias were reduced: (1) Three patients had nonsustained VT on beta-blockers, and none of them had VT on combination therapy. (2) The number of ventricular ectopics during the whole exercise test went down from 78 +/- 59 beats to 6 +/- 8 beats; the ratio of ventricular ectopic to sinus beats during the 10-second period recorded at the time of the worst ventricular arrhythmia went down from 0.9 +/- 0.4 to 0.2 +/- 0.2. One patient with recurrent spontaneous VT leading to multiple shocks from her implanted cardioverter-defibrillator (ICD) despite maximal beta-blocker therapy (14 ICD shocks over 6 months while on beta-blockers) has remained free of arrhythmias (for 7 months) since the addition of verapamil therapy. CONCLUSIONS: This preliminary evidence suggests that beta-blockers and calcium blockers could be better than beta-blockers alone for preventing exercise-induced arrhythmias in CPVT.     

Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice

Repolarization Lability in Casq2?/? Mice . Background: Calsequestrin‐2 (CASQ2) is a Ca²⁺ buffering protein of myocardial sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated in Casq2 ?/? mice. Repolarization lability (RL)—beat‐to‐beat variability in the T wave morphology—has been reported in long‐QT syndrome, but has not been evaluated in CPVT. Methods and Results: ECG from Casq2 ?/? mice was evaluated with respect to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT) to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice (3‐month‐old males, 5 animals of each genotype) and ECG before and after isoproterenol administration in anesthetized mice was analyzed. Average HR in sinus rhythm (SR), occurrence of nonsinus rhythm and RL were quantified. HR was slower in Casq2 ?/? animals. Accelerated junctional rhythm (JR) occurred more frequently in Casq2 ?/? mice and often preceded VT. In Casq2 ?/? mice, HR increased prior to VT onset, prior to onset of JR and on transition from JR to VT. RL increased during progression from SR to VT and after isoproterenol administration in Casq2 ?/?, but not in Casq2+/+ animals. Isoproterenol did not increase repolarization alternans in either genotype. Conclusions: Accelerated JR, likely caused by triggered activity in His/Purkinje system, occurs frequently in Casq2 ?/? mice. The absence of CASQ2 results in increased RL. The increase in HR and in RL precede onset of arrhythmias in this CPVT model. Nonalternans RL precedes ventricular arrhythmia in wider range of conditions than previously appreciated. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1355‐1363, December 2012)     

Perioperative correlates of malignant ventricular tachyarrhythmias complicating coronary surgery

Summary Sustained ventricular tachyarrhythmias (VT), such as monomorphic or polymorphic ventricular tachycardia, and ventricular fibrillation, represent the most serious arrhythmic events that can complicate the postoperative course of coronary artery bypass grafting (CABG). The perioperative factors potentially associated with post-CABG sustained VT onset have not been thoroughly investigated. As a consequence, the aim of our study was to identify which perioperative variables might predict post-CABG VT occurrence. One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institute were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). Univariate analysis revealed that VT patients were significantly younger (54.8 ± 6.6 vs 60.1 ± 8.8,P = 0.038), exhibited more severe coronary artery disease (CAD) (no. of diseased vessels, 2.92 ± 0.3 vs 2.45 ± 0.7,P = 0.023; and percentage of patients with three-vessel CAD, 91.7 vs 57.3%,P = 0.043), and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs, 76.9 vs 38.8%,P = 0.018) Moreover, VT patients more frequently developed intra- or postoperative myocardial infarction (total CK > 1000, 76.9 vs 38%,P = 0.016; and MB-CK > normal range, 72.7 vs 30.7%,P = 0.014), electrolyte derangement (84.6 vs 45.6%,P = 0.017), and a severe hemodynamic impairment (need for intra-aortic balloon pump (IABP), 23 vs 2.9%,P = 0.009). On multivariate analysis, total CK > 1000, postoperative electrolyte imbalance, the need for three or more CABGs, and for IABP all were independent correlates for VT. In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors, such as acute ischemia, electrolytic disorders, and sudden hemodynamic impairment. This paper is supported by Dottorato di Ricerca in Cardio Chirurgia — Seconda Universita' Napoli     

儿茶酚胺敏感性多形性室性心动过速基因特异性管理

儿茶酚胺敏感性多形性室性心动过速(catecholaminergic polymorphic ventricular tachycardia，CPVT)是一种罕见的遗传性疾病，与基因突变导致的心肌细胞内钙稳态的失衡有关，运动或情绪激动可诱发致命性的室性心律失常。CPVT的诊断基于肾上腺素引起的双向性或多形性室性心动过速，部分患者通过基因检测确诊。在治疗上可通过内、外科方法，抑制或阻断肾上腺素对心肌钙稳态的影响。未正规治疗的患者死亡率高，且猝死常为首发症状。文章阐述CPVT的遗传学新发现及其对临床管理的影响，同时阐述基因检测的局限性和级联筛查的最佳应用。     

Ventricular tachycardia. Diagnostic spectrum and therapeutic measures

The origin of ventricular tachycardia lies in the ventricular tissue and includes a variety of symptoms such as monomorphic and polymorphic ventricular tachyarrhythmia (VT), ventricular flutter and ventricular fibrillation. Due to transitions of one form of VT to another, any form of VT incurs in principal the risk of cardiac failure. Apart from different electrophysiologic mechanisms such as reentry or triggered activity, any occurrence of VT has to be considered in an individual context: VT can be caused by structural heart disease such as coronary artery disease or dilative cardiomyopathy, or primary electrical disease such as long or short QT syndromes or can even occur without any detectable cause (idiopathic VT). Correct identification of the underlying cause of the arrhythmia is essential for the prognosis, differential therapy and long-term treatment of patients.     

Ventrikuläre Tachykardien

The origin of ventricular tachycardia lies in the ventricular tissue and includes a variety of symptoms such as monomorphic and polymorphic ventricular tachyarrhythmia (VT), ventricular flutter and ventricular fibrillation. Due to transitions of one form of VT to another, any form of VT incurs in principal the risk of cardiac failure. Apart from different electrophysiologic mechanisms such as reentry or triggered activity, any occurrence of VT has to be considered in an individual context: VT can be caused by structural heart disease such as coronary artery disease or dilative cardiomyopathy, or primary electrical disease such as long or short QT syndromes or can even occur without any detectable cause (idiopathic VT). Correct identification of the underlying cause of the arrhythmia is essential for the prognosis, differential therapy and long-term treatment of patients.     

Morphological findings in apparently idiopathic ventricular tachycardia. An echocardiographic haemodynamic and histologic study

In order to investigate the anatomic substrate of ‘idiopathic’ventricular tachycardia (VT) 10 patients with chronic recurrentVT and no apparent sign of heart disease underwent an echocardiographic,haemodynamic and histologic study (5 males, 5 females: meanage=40±11 years). In the patients with a left bundle branch block morphology ofVT (7 cases), four showed findings compatible with an arrhythmogenicright ventricular dysplasia or a right ventricular cardiomyopathy.In the other three all examinations were normal with the exceptionof endomyocardial biopsy, which showed slight non specific changesin two. Of the remaining 3 cases (characterized by a right bundlebranch block morphology of VT or by the presence of polymorphicVT) one had histologic evidence of myocarditis while anotherdeveloped dilated cardiomyopathy. Macroscopic and/or microscopic ventricular abnormalities arefrequently found in patients with VT which appears idiopathic.In these cases myocardial disease is frequently progressive,despite optimal control of VT.     

Peripartum management of a patient with catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal cardiac channelopathy characterized by episodes of ventricular tachycardia (VT) during exercise or in stressful situations. As the peripartum period creates a stressful environment, we describe our approach of this rare condition in a very common situation, child birth.     

儿茶酚胺介导的多形性室速研究进展

儿茶酚胺介导的多形性室速是一种少见却严重的遗传性心律失常,表现为无器质性心脏病的个体在运动或激动时发生双向性、多形性室速导致发作性晕厥及进展为心室颤动导致猝死。心肌细胞肌浆网异常释放钙离子使细胞内钙离子超载引起的延迟后除极可能是儿茶酚胺介导的多形性室速发生的机制。目前已知的和儿茶酚胺介导的多形性室速相关的基因为常染色体显性遗传的RyR2（位于1q42.1-q43）和常染色体隐性遗传的CASQ2（位于1p13.3-p11）。治疗：β-阻断剂适用于所有临床症状的个体和可能有RyR2突变而没有心脏事件（晕厥）或运动试验诱发的室性心律失常等病史的个体。反复心脏骤停患者需植入式心律转复除颤器。每6至12个月随访以监测疗效。患者所有的一级亲属,都应予心脏评估。