Short-coupled Variant Research Articles

Mechanisms of torsades de pointes: an update.

Torsades de Pointes (TdP) refers to a polymorphic ventricular tachycardia (VT) with undulating QRS axis that occurs in long QT syndrome (LQTS), although the term has been used to describe polymorphic ventricular tachyarrhythmias in which QT intervals are not prolonged, such as short-coupled variant of TdP currently known as short-coupled ventricular fibrillation (VF) and Brugada syndrome. Extensive works on LQTS-related TdP over more than 50 years since it was first recognized by Dessertennes who coined the French term meaning "twisting of the points", have led to current understanding of the electrophysiological mechanism that TdP is initiated by triggered activity due to early afterdepolarization (EAD) and maintained by reentry within a substrate of inhomogeneous repolarization. While a recently emerging notion that steep voltage gradients rather than EADs are crucial to generate premature ventricular contractions provides additions to the initiation mode, the research to elucidate the maintenance mechanism hasn't made much progress. The reentrant activity that produces the specific form of VT is not well characterized. We have conducted optical mapping in a rabbit model of electrical storm by electrical remodeling (QT prolongation) due to chronic complete atrioventricular block and demonstrated that a tissue-island with prolonged refractoriness due to enhanced late Na+ current (INa-L) contributes to the generation of drifting rotors in a unique manner, which may explain the ECG characteristic of TdP. Moreover, we have proposed that the neural Na+ channel NaV1.8-mediated INa-L may be a new player to form the substrate for TdP. Here we discuss TdP mechanisms by comparing the findings in electrical storm rabbits with recently published studies by others in simulation models and human and animal models of LQTS.

Loss-of-function mutations in cardiac ryanodine receptor channel cause various types of arrhythmias including long QT syndrome.

Gain-of-function mutations in RYR2, encoding the cardiac ryanodine receptor channel (RyR2), cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Whereas, genotype-phenotype correlations of loss-of-function mutations remains unknown, due to a small number of analysed mutations. In this study, we aimed to investigate their genotype-phenotype correlations in patients with loss-of-function RYR2 mutations. We performed targeted gene sequencing for 710 probands younger than 16-year-old with inherited primary arrhythmia syndromes (IPAS). RYR2 mutations were identified in 63 probands, and 3 probands displayed clinical features different from CPVT. A proband with p.E4146D developed ventricular fibrillation (VF) and QT prolongation whereas that with p.S4168P showed QT prolongation and bradycardia. Another proband with p.S4938F showed short-coupled variant of torsade de pointes (scTdP). To evaluate the functional alterations in these three mutant RyR2s and p.K4594Q previously reported in a long QT syndrome (LQTS), we measured Ca2+ signals in HEK293 cells and HL-1 cardiomyocytes as well as Ca2+-dependent [3H]ryanodine binding. All mutant RyR2s demonstrated a reduced Ca2+ release, an increased endoplasmic reticulum Ca2+, and a reduced [3H]ryanodine binding, indicating loss-of-functions. In HL-1 cells, the exogenous expression of S4168P and K4594Q reduced amplitude of Ca2+ transients without inducing Ca2+ waves, whereas that of E4146D and S4938F evoked frequent localized Ca2+ waves. Loss-of-function RYR2 mutations may be implicated in various types of arrhythmias including LQTS, VF, and scTdP, depending on alteration of the channel activity. Search of RYR2 mutations in IPAS patients clinically different from CPVT will be a useful strategy to effectively discover loss-of-function RYR2 mutations.

Successful bailout of refractory ventricular fibrillation originating from the moderator band using bipolar ablation in a patient with short-coupled variant of torsade de pointes.

Successful bailout of refractory ventricular fibrillation originating from the moderator band using bipolar ablation in a patient with short-coupled variant of torsade de pointes.

Catheter ablation of short-coupled variant of torsade de pointes

BackgroundThe short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping.Methods and resultsWe retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up.Conclusion3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.Graphic abstract

Idiopathic Ventricular Fibrillation: Diagnosis, Ablation of Triggers, Gaps in Knowledge, and Future Directions.

Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion made when no underlying cause is identified in a cardiac arrest survivor. Although the frequency of this diagnosis has declined over time due to advances in diagnostic techniques, it remains a substantial cause of sudden cardiac arrest. Further, IVF tends to recur. This article reviews the criteria for diagnosis, patient characteristics, the two primary arrhythmic phenotypes—short-coupled variant of torsades de pointes and recurrent paroxysmal IVF—and the electrophysiologic features, treatment, and ablation of premature ventricular complexes that can trigger IVF.

A TRIGGER FOR AN ARRHYTHMIC STORM: SHORT-COUPLED VARIANT TORSADE DE POINTES

Short-coupled variant of torsade de pointes (SCV-TdP) is an uncommon type of polymorphic ventricular tachycardia with unknown etiology. It is triggered by premature ventricular complexes with remarkably short coupling interval (<300 ms), in the absence of QT prolongation and structural heart disease

Cardiac Arrest Secondary to Short-Coupled TdP: A Case Report

Background: The short-coupled variant of Torsade de Pointes (Sc-TdP) is rare and causes Torsade-like polymorphic ventricular tachycardia (VT) without the classical QT-prolongation. It is initiated by a remarkably short coupling interval (<300 ms). The arrhythmia is important to identify as the treatment differs from another traditional polymorphic VT.

Cardiac Arrest Secondary to Short-Coupled TdP: A Case Report

Background: The short-coupled variant of Torsade de Pointes (Sc-TdP) is rare and causes Torsade-like polymorphic ventricular tachycardia (VT) without the classical QT-prolongation. It is initiated by a remarkably short coupling interval (<300 ms). The arrhythmia is important to identify as the treatment differs from another traditional polymorphic VT.

Successful catheter ablation of premature ventricular contractions triggering torsade de pointes in a small infant with histiocytoid cardiomyopathy: a case report.

BackgroundA short-coupled variant of torsade de pointes (ScTdP) is rare and resistant to medical treatment. There has not been a reported catheter ablation (CA) of a short-coupled premature ventricular contraction (PVC) triggering ScTdP in an infant.Case summaryA neonate was referred to our hospital on the day of birth for Wolff–Parkinson–White syndrome, repeated episodes of supraventricular tachycardia, and a left ventricular non-compaction. She underwent CA of an accessory pathway at 72 days of age. On the 5th day after ablation, she had recurrent TdP episodes resistant to various antiarrhythmic drugs and received extracorporeal membrane oxygenation at 86 days of age. She underwent CA of PVCs triggering TdP at 122 days of age and a weight of 3.4 kg. Two types of PVCs triggering TdP were successfully ablated, which originated from the right ventricle (RV). Pre-potentials were recorded at the earliest ventricular activation sites of the targeted PVCs. After the ablation, she had no TdP episodes and the cardiac assist device was removed. However, she died of uncontrolled heart failure at 6 months of age. The histological findings were compatible with histiocytoid cardiomyopathy and abnormal cells were distributed throughout both ventricles. At the ablation site, fibrotic transmural lesions were noted in the RV wall.DiscussionThe PVCs triggering TdP were successfully ablated in a 4-month-old girl with histiocytoid cardiomyopathy. The PVCs were likely caused by triggered activity and associated with abnormal Purkinje cells.

Short-coupled variant of torsade de pointesに対しベプリジルが有効であった1例

Short-coupled variant of torsade de pointesに対しベプリジルが有効であった1例

An RyR2 mutation found in a family with a short-coupled variant of torsade de pointes

An RyR2 mutation found in a family with a short-coupled variant of torsade de pointes

A type 2 ryanodine receptor variant associated with reduced Ca2+ release and short-coupled torsades de pointes ventricular arrhythmia

Ventricular fibrillation may be caused by premature ventricular contractions (PVCs) whose coupling intervals are <300 ms, a characteristic of the short-coupled variant of torsades de pointes (scTdP). The purpose of this study was to analyze the underlying cardiac ryanodine receptor (RyR2) variants in patients with scTdP. Seven patients with scTdP (mean age 34 ± 12 years; 4 men and 3 women) were enrolled in this study. The RyR2 gene was screened by targeted gene sequencing methods; variant minor allele frequency was confirmed in 3 databases; and the pathogenicity was investigated in silico analysis using multiple tools. The activity of wild-type and mutant RyR2 channels was evaluated by monitoring Ca2+ signals of HEK293 cells with a [3H]ryanodine binding assay. The mean coupling interval of PVCs was 282 ± 13 ms. The 12-lead electrocardiogram had no specific findings except PVCs with an extremely short-coupling interval. Genetic analysis revealed 3 novel RyR2 variants and 1 polymorphism, all located in the cytoplasmic region. p.Ser4938Phe was not detected in 3 databases, and in silico analysis indicated its pathogenicity. In functional analysis, p.Ser4938Phe demonstrated loss of function and impaired RyR2 channel Ca2+ release, while 2 other variants, p.Val1024Ile and p.Ala2673Val, had mild gain-of-function effects but were similar to the polymorphism p.Asn1551Ser. We identified an RyR2 variant associated with reduced Ca2+ release and short-coupled torsades de pointes ventricular arrhythmia. The mechanisms of arrhythmogenesis remain unclear.

突然死の家族歴を有しShort-coupled variant of torsade de pointesと考えられた若年女性の1例

突然死の家族歴を有しShort-coupled variant of torsade de pointesと考えられた若年女性の1例

Short-coupled variant of torsade de pointes — an important cause of syncope and sudden death

We describe 5 cases of a rare and often lethal arrhythmia: short-coupled variant of torsade de pointes. In the light of quitecharacteristic electrocardiograms and clinical picture of this arrhythmia, we consider the name 'short-coupled variant torsade de pointes' as more appropriate than, the more commonly applied term for such cases - 'idiopathic ventricular fibrillation'. We suggest that in patients with unexplained syncope, normal echocardiogram, normal QT interval and frequent premature ventricular contraction with short coupling this arrhythmogenic entity should be suspected. We stress that these premature beats are often misclassified as supraventricular since the two major factors (slow initial depolarisation of the working myocardium and structural abnormalities of the left ventricle) responsible for typical morphological features of ventricular beats are lacking.

Ablation of idiopathic ventricular fibrillation targeting short coupled ventricular premature contractions originating from a right ventricular papillary muscle

We describe a 38-year-old male who experienced several episodes of syncope after having ventricular fibrillation. The electrocardiographic monitoring after his hospitalization revealed repetitive polymorphic ventricular tachycardias. All polymorphic ventricular tachycardias were consistently initiated by a short-coupled monomorphic ventricular premature contraction (VPC). This VPC was suggested to originate from the inferoposterior region of the right ventricle (RV). Radiofrequency catheter ablation targeting the VPC was successfully performed, and the CARTO merge system (Biosense Webster Inc., Diamond Bar, CA, USA) revealed that the culprit region was the root of the posterior papillary muscle of the RV. A subsequent follow-up of 15 months has been uneventful.<Learning objective: This is a case report of idiopathic ventricular fibrillation (IVF) triggered by a ventricular premature contraction (VPC) from the posterior papillary muscle of the right ventricle. We can learn about the relationship between the anatomical structure and the possible mechanisms of the short-coupled variant of Torsade de Pointes.>

A case of electrical storm in a patient with short-coupled variant of torsade de pointes

Short-coupled variant of torsade de pointes (TdP) is an uncommon variant of polymorphic ventricular tachycardia with unknown etiology. It is initiated by a closely coupled premature ventricular complex (<300 ms) in the absence of QT prolongation and structural heart disease. Verapamil seems to be the only drug able to suppress the arrhythmia but, as it does not reduce the risk of sudden death, implantation of a cardioverter-defibrillator (ICD) is recommended. We describe the case of a 46-year-old woman referred to our Emergency Department because of palpitations. The initial ECG showed a non-sustained polymorphic ventricular tachycardia with a borderline QTc interval (450 ms). After admission, the patient experienced an episode of TdP that started after short-coupling interval (280 ms) between the last sinus beat and the ventricular premature beat (VPB). DC-shock restored sinus rhythm. Physical examination, exercise testing, echocardiography and cardiac magnetic resonance were all normal, and she had no family history of sudden cardiac death. Baseline ECG showed sinus rhythm and unifocal VPBs with the same morphology of the VPB of TdP. The patient received an ICD and was treated medically with verapamil. She was discharged from the hospital on oral therapy with verapamil (240 mg/day), and she was free of recurrence 12 months later when an electrical storm occurred. The verapamil dose was therefore increased to 480 mg/day. Unifocal VPBs disappeared from her body surface ECG, and the subsequent 3-year follow-up was uneventful.

Catecholaminergic Polymorphic Ventricular Tachycardia

Sudden death because of cardiac arrhythmias in the young is a devastating event and remains underdiagnosed. The primary electric disorders responsible for polymorphic ventricular tachycardia (VT) or ventricular fibrillation are long-QT syndrome, Brugada syndrome, the short-coupled variant of torsades de pointes, short-QT syndrome, and catecholaminergic polymorphic VT (CPVT). CPVT is a rare arrhythmogenic disorder characterized by adrenergic-induced bidirectional and polymorphic VT. The prevalence of the disease is estimated to be 1:10 000 in Europe. The first case was reported in 1975,1 followed by our first series of patients.2,3 Key features include polymorphic VT reproducibly induced during exercise tests, isoproterenol infusion, or emotion and exercise. CPVT occurs in children and adolescents and causes syncope and sudden cardiac death at a young age, in the absence of structural heart disease. The resting ECG, including the QTc interval, is normal. The mortality of CPVT is extremely high, reaching 31% by the age of 30 years when untreated.1,2 The estimated 4- and 8-year cardiac event rates were 33% and 58%, respectively, in our series of patients without β-blockers.3 There is a clear correlation between the age of the first syncope and the severity of the disease, with a worse prognosis in the case of early occurrence. β-Blockers without sympathomimetic activity are clinically effective in reducing syncope.3 However, arrhythmic event rate with β-blocker therapy remains significant, suggesting the need for alternate pharmacological and nonpharmacological therapies, which will be discussed. With the advancements of molecular genetics and the identification of mutations in the genes encoding the cardiac ryanodine receptor and cardiac calsequestrin 2 in patients with CPVT, the central role of the intracellular calcium dysregulation in myocardial cells is progressively better understood through expression studies and murine models. Therapies targeting this dysregulation have been actually developed. Family …

Catheter Ablation of Ventricular Fibrillation: State of the Art

Catheter ablation of the triggering ventricular premature beats (VPBs) is feasible for idiopathic and ischemic ventricular fibrillation (VF) and can be used for a bailout therapy of VF storm. Also, it can reduce the number of the shock from an implantable defibrillator, one of the poor prognostic factors. In VF or polymorphic ventricular tachycardia (VT) from right ventricular outflow tract (RVOT), suppression of VF was achieved by catheter ablation at RVOT or pulmonary artery. In the short-coupled variant of torsade de pointes and ischemic VF, VF was suppressed by catheter ablation of the Purkinje network. Focal firing from Purkinje fiber and reentry at the Purkinje network may play an important role in the initiation and perpetuation of VF. The same approach with good short-term results has been reported in a small number of patients with other heart diseases (i.e., amyloidosis, chronic myocarditis, nonischemic cardiomyopathy, Brugada syndrome, Long-QT syndrome, and catecholaminergic polymorphic VT).

Pregnancy and Short‐Coupled Torsades de Pointes

This 24-year-old woman had incessant polymorphic ventricular tachycardia (PVT) during week 24 of her pregnancy and received over 200 implantable cardioverter-defibrillator discharges. She failed to respond to quinidine, magnesium, isoproterenol, amiodarone, esmolol, and cilostazol during her PVT storm, although her dramatic response to verapamil was consistent with the diagnosis of short-coupled variant of torsades de pointes. The case illustrated the utility of extracorporeal membrane oxygenation during refractory PVT, while attempting diagnostic and therapeutic pharmacologic maneuvers.

Premature Ventricular Complexes as a Trigger for Ventricular Fibrillation

The mechanisms that trigger ventricular fibrillation (VF) are poorly understood. The aim of this study was to analyze the initiation of VF in electrograms stored in implantable cardioverter-defibrillators (ICDs). We analyzed ICD electrograms from patients who had suffered at least one episode of VF. Of 250 patients with ICDs, 13 (10 male and 3 female, age 49+/-22 years) had at least one episode of VF. The diagnoses were Brugada syndrome (n=4), ischemic heart disease (n=3), dilated cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), short-coupled variant of torsades de pointes (n=1), endocardial fibroelastosis (n=1) and idiopathic VF (n=1). In 7 patients, VF was the reason for ICD implantation. Overall, 31 episodes of VF were recorded, including three episodes of arrhythmic storm. In the 7 patients who had more than one episode of VF (within minutes or up to 3 years apart), all episodes started with premature ventricular complexes (PVCs) that had the same morphology and similar coupling intervals. A short-long-short cycle was observed in 2 patients. In 21 episodes, PVCs that did not trigger VF were observed during sinus rhythm. There was no significant difference between them and PVCs that did trigger VF in terms of morphology, coupling interval (409+/-121 ms vs. 411+/-123 ms) or the preceding sinus rhythm RR interval (801+/-233 ms vs. 793+/-230 ms). Spontaneous VF in the form of an arrhythmic storm or an isolated episode were triggered by PVCs. On occasions, PVCs preceded VF without triggering it.