Loss of consciousness and convulsion induced by a ventricular tachycardia mimicking epilepsy in a patient with noncompaction cardiomyopathy: a case report

Convulsions and loss of consciousness can be caused by, among other things, arrhythmias, conduction disorders or epilepsy. In clinical practice it can be difficult to distinguish between these causes of syncope, even for well-trained specialists. Patients with cardiac syncope have a substantial risk of subsequent sudden death. We present a patient with previously unknown noncompaction cardiomyopathy in whom syncope induced by ventricular tachycardia was misinterpreted as epilepsy. We present this case report in order to underline the necessity for cardiological assessment in patients with assumed mild epilepsy or syncope of unknown origin.     

Bundle branch reentrant ventricular tachycardia

Bundle branch reentrant (BBR) tachycardia is an uncommon form of ventricular tachycardia (VT) incorporating both bundle branches into the reentry circuit. The arrhythmia is usually seen in patients with an acquired heart disease and significant conduction system impairment, although patients with structurally normal heart have been described. Surface ECG in sinus rhythm (SR) characteristically shows intraventricular conduction defects. Patients typically present with presyncope, syncope or sudden death because of VT with fast rates frequently above 200 beats per minute. The QRS morphology during VT is a typical bundle branch block pattern, usually left bundle branch block, and may be identical to that in SR. Prolonged His-ventricular (H-V) interval in SR is found in the majority of patients with BBR VT, although some patients may have the H-V interval within normal limits. The diagnosis of BBR VT is based on electrophysiological findings and pacing maneuvers that prove participation of the His- Purkinje system in the tachycardia mechanism. Radiofrequency catheter ablation of a bundle branch can cure BBR VT and is currently regarded as the first line therapy. The technique of choice is ablation of the right bundle. The reported incidence of clinically significant conduction system impairment requiring implantation of a permanent pacemaker varies from 0% to 30%. Long-term outcome depends on the underlying cardiac disease. Patients with poor systolic left ventricular function are at risk of sudden death or death from progressive heart failure despite successful BBR VT ablation and should be considered for an implantable cardiovertor-defibrillator.     

An inappropriate defibrillator shock during ventricular tachycardia

Ventricular oversensing in patients with defibrillators is an infrequent but deleterious condition. We report a patient with a cardiac resynchronization–defibrillation device that presented with hyperkalemia and syncope. Device interrogation revealed ventricular double-counting within the QRS of a slow ventricular tachycardia, resulting detection of the slow ventricular tachycardia in the ventricular fibrillation zone, and delivery of an effective therapy, below device programmed detection rate. This case of defibrillator inappropriate detection emphasizes the relevance of device electrogram interrogation in order to minimize inappropriate therapies.     

Efficacy of RyR2 inhibitor EL20 in induced pluripotent stem cell-derived cardiomyocytes from a patient with catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome that often leads to sudden cardiac death. The most common form of CPVT is caused by autosomal-dominant variants in the cardiac ryanodine receptor type-2 (RYR2) gene. Mutations in RYR2 promote calcium (Ca²⁺) leak from the sarcoplasmic reticulum (SR), triggering lethal arrhythmias. Recently, it was demonstrated that tetracaine derivative EL20 specifically inhibits mutant RyR2, normalizes Ca²⁺ handling and suppresses arrhythmias in a CPVT mouse model. The objective of this study was to determine whether EL20 normalizes SR Ca²⁺ handling and arrhythmic events in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from a CPVT patient. Blood samples from a child carrying RyR2 variant RyR2 variant Arg-176-Glu (R176Q) and a mutation-negative relative were reprogrammed into iPSCs using a Sendai virus system. iPSC-CMs were derived using the Stemdiff^TM kit. Confocal Ca²⁺ imaging was used to quantify RyR2 activity in the absence and presence of EL20. iPSC-CMs harbouring the R176Q variant demonstrated spontaneous SR Ca²⁺ release events, whereas administration of EL20 diminished these abnormal events at low nanomolar concentrations (IC₅₀ = 82 nM). Importantly, treatment with EL20 did not have any adverse effects on systolic Ca²⁺ handling in control iPSC-CMs. Our results show for the first time that tetracaine derivative EL20 normalized SR Ca²⁺ handling and suppresses arrhythmogenic activity in iPSC-CMs derived from a CPVT patient. Hence, this study confirms that this RyR2-inhibitor represents a promising therapeutic candidate for treatment of CPVT.     

Whole‐exome sequencing identifies a novel mutation of GPD1L (R189X) associated with familial conduction disease and sudden death

Cardiac conduction disease (CCD) is a serious disorder and the leading cause of mortality worldwide. It is characterized by arrhythmia, syncope or even sudden cardiac death caused by the dysfunction of cardiac voltage‐gated channel. Previous study has demonstrated that mutations in genes encoding voltage‐gated channel and related proteins were the crucial genetic lesion of CCD. In this study, we employed whole‐exome sequencing to explore the potential causative genes in a Chinese family with ventricular tachycardia and syncope. A novel nonsense mutation (c.565C>T/p.R189X) of glycerol‐3‐phosphate dehydrogenase‐like (GPD1L) was identified and co‐segregated with the affected family members. GPD1L is a crucial interacting protein of SCN5A, a gene encoded sodium channel α‐subunit Na_v1.5 and mainly associated with Brugada syndrome (BrS). The novel mutation (c.565C>T/p.R189X) may result in a premature stop codon at position 189 in exon 4 of the GPD1L gene and lead to functional haploinsufficiency of GPD1L due to mRNA carrying this mutation will be degraded by nonsense‐mediated mRNA decay, which has been confirmed by Western blot in HEK293 cells transfected HIS‐GPD1L plasmid. The levels of GPD1L decreasing may disturb the function of Na_v1.5 and induce arrhythmia and syncope in the end. In conclusion, our study not only further supported the important role of GPD1L in CCD, but also expanded the spectrum of GPD1L mutations and will contribute to the genetic diagnosis and counselling of families with CCD.     

Catheter ablation of fascicular ventricular tachycardia

Fascicular ventricular tachycardia (VT) is an idiopathic VT with right bundle branch block morphology and left-axis deviation occuring predominantly in young males. Fascicular tachycardia has been classified into three subtypes namely, left posterior fascicular VT, left anterior fascicular VT and upper septal fascicular VT. The mechanism of this tachycardia is believed to be localized reentry close to the fascicle of the left bundle branch. The reentrant circuit is composed of a verapamil sensitive zone, activated antegradely during tachycardia and the fast conduction Purkinje fibers activated retrogradely during tachycardia recorded as the pre Purkinje and the Purkinje potentials respectively. Catheter ablation is the preferred choice of therapy in patients with fascicular VT. Ablation is carried out during tachycardia, using conventional mapping techniques in majority of the patients, while three dimensional mapping and sinus rhythm ablation is reserved for patients with nonmappable tachycardia.     

Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT.Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca²⁺ imaging and [³H]ryanodine binding.A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca²⁺ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine.The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias.Key words: arrhythmia, calcium, death sudden, genetics, ion channels     

Idiopathic submitral left ventricular aneurysm: an unusual substrate for ventricular tachycardia in Caucasians

Annular submitral aneurysms have been rarely reported in Caucasians. They are typically diagnosed in non-white adults who present with severe mitral regurgitation, heart failure, systemic embolism, ventricular arrhythmias, and sudden cardiac death. In this article, we describe the case of a white woman, presenting with ventricular tachycardia, who had a large submitral left ventricular aneurysm diagnosed incidentally during coronary angiography.     

Premature Ventricular Contractions and Non-sustained Ventricular Tachycardia: Association with Sudden Cardiac Death,Risk Stratification,and Management Strategies

Premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT) are frequently encountered and a marker of electrocardiomyopathy. In some instances, they increase the risk for sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. While often associated with a primary cardiomyopathy, they have also been known to cause tachycardia-induced cardiomyopathy in patients without preceding structural heart disease. Medical therapy including beta-blockers and class III anti-arrhythmic agents can be effective while implantable cardiac defibrillators (ICD) are indicated in certain patients. Radiofrequency ablation (RFA) is the preferred, definitive treatment in those patients that improve with anti-arrhythmic therapy, have tachycardia-induced cardiomyopathy, or have certain subtypes of PVCs/NSVT. We present a review of PVCs and NSVT coupled with case presentations on RFA of fascicular ventricular tachycardia, left-ventricular outflow tract ventricular tachycardia, and Purkinje arrhythmia leading to polymorphic ventricular tachycardia.     

A Case of Inappropriate Therapies for Atrial Flutter From a Subcutaneous ICD

Hypertrophic cardiomyopathy’s (HCM) association with sudden cardiac death is well recognised. The risk of sudden cardiac death is known to increase when there is a history of unexplained syncope, abnormal blood pressure response during exercise, severe left ventricular hypertrophy or a family history of unexplained death.Implantable Cardioverter Defibrillator (ICD) implantation has been widely used for primary and secondary prevention of sudden cardiac death (SCD) in people with HCM. Subcutaneous ICD (S-ICD) therapy has been developed to overcome some of the problems associated with the transvenous leads used in conventional ICDs.In this article, we report the use of S-ICD in a patient with HCM and multiple risk factors for sudden cardiac death, this device had to be extracted due to recurrent inappropriate shocks caused by over sensing of atrial flutter and failure to treat a VT episode. We are not aware of any reports of inappropriate shocks caused by atrial flutter in people with a S-ICD.     

Arrhythmogenic right ventricular cardiomyopathy/dysplasia

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator. Young age, family history of juvenile sudden death, QRS dispersion ≥ 40 ms, T-wave inversion, left ventricular involvement, ventricular tachycardia, syncope and previous cardiac arrest are the major risk factors for adverse prognosis. Preparticipation screening for sport eligibility has been proven to be effective in detecting asymptomatic patients and sport disqualification has been life-saving, substantially declining sudden death in young athletes.     

Simulated Interactions between a Class III Antiarrhythmic Drug and a Figure 8 Reentry

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. Simulations are ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR.     

The rationale of using cerebral embolic protection devices during transcatheter aortic valve implantation

Aortic valve stenosis is one of the most common valvular abnormalities, which can manifest as angina, syncope, dyspnoea and sudden cardiac death. Transcath     

Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT.

Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca2+ imaging and [3H]ryanodine binding.

A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca2+ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine.

The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias.     

Left ventricular false tendons

Left ventricular false tendons (LVFTs) are fibromuscular structures, connecting the left ventricular free wall or papillary muscle and the ventricular septum.There is some discussion about safety issues during intense exercise in athletes with LVFTs, as these bands have been associated with ventricular arrhythmias and abnormal cardiac remodelling. However, presence of LVFTs appears to be much more common than previously noted as imaging techniques have improved and the association between LVFTs and abnormal remodelling could very well be explained by better visibility in a dilated left ventricular lumen.Although LVFTs may result in electrocardiographic abnormalities and could form a substrate for ventricular arrhythmias, it should be considered as a normal anatomic variant. Persons with LVFTs do not appear to have increased risk for ventricular arrhythmias or sudden cardiac death.     

Risk Stratification in Young Patients With Channelopathies

Identifying the young patient at risk of malignant arrhythmias and sudden cardiac death remains a challenge. It is increasingly recognised that sudden death, syncope and aborted cardiac arrest at a young age in patients with a structurally normal heart may be the result of various ion channel disorders - the channelopathies. The approach to risk stratification involves a combination of the clinical presentation, taken in conjunction with the family history, genetic testing, invasive electrophysiological studies or other provocative tests where appropriate and feasible. A logical approach to risk stratification in some of the commoner channelopathies seen in paediatric practice is presented.     

Confounding factors leading to misdiagnosing ventricular tachycardia as supraventricular in the emergency room

Studies conducted during the last 50 years have proposed electrocardiographic criteria and algorithms to determine if a wide QRS tachycardia is ventricular or supraventricular in origin. Sustained ventricular tachycardia is an uncommon reason for consultation in the emergency room. The latter and the complexity of available electrocardiographic diagnostic criteria and algorithms result in frequent misdiagnoses. Good hemodynamic tolerance of tachycardia in the supine position does not exclude its ventricular origin. Although rare, ventricular tachycardia in patients with and without structural heart disease may show a QRS duration <120 ms. Interruption of tachycardia by coughing, carotid sinus massage, Valsalva maneuver, or following the infusion of adenosine or verapamil should not discard the ventricular origin of the arrhythmia. In patients with regular, uniform, sustained broad QRS tachycardia, the presence of structural heart disease or A-V dissociation strongly suggest its ventricular origin. Occasionally, ventricular tachycardia can present with AV dissociation without this being evident on the 12-lead ECG. Cardiac auscultation, examination of the jugular venous pulse, and arterial pulse palpation provide additional clues for identifying A-V dissociation during tachycardia. This paper does not review the electrocardiographic criteria for categorizing tachycardia as ventricular but rather why emergency physicians misdiagnose these patients.     

Successful termination of ventricular tachycardia with intrinsic anti-tachycardia pacing

Intrinsic anti-tachycardia pacing (iATP) is a novel automated ATP algorithm that employs post-pacing interval (PPI) to design the next ATP sequence based on an analysis of the prior failed ATP sequence. A patient with hypertrophic cardiomyopathy received an implantable cardioverter-defibrillator (ICD) (Cobalt™ XT DR, Medtronic, Minneapolis, MN, USA) following an episode of syncope due to macro-reentrant ventricular tachycardia (VT) (right bundle branch block configuration, cycle length [CL] 280 ms). The VF zone was set to VTCL <300 ms and iATP therapy was prescribed before and during capacitor charging. The iATP was initiated when VT recurred 3 months later. The first attempt with an assumption of 150 ms propagation time from the pacing site to the VT circuit (9 pulses) could not reset the VT, leaving a PPI of 650 ms. A subsequent attempt involving 20 pulses with an assumption of 250 ms propagation time terminated the VT. Failure to reach the circuit is a major cause of unsuccessful ATP. In this regard, iATP is expected to have theoretical advantages over empirical and traditional ATP therapies. To the best of our knowledge, this is the first intracardiac electrogram illustrating how automated precision ATP terminates VT in a clinical setting.     

Ventricular tachycardia in the absence of structural heart disease

In up to 10% of patients who present with ventricular tachycardia (VT), obvious structural heart disease is not identified. In such patients, causes of ventricular arrhythmia include right ventricular outflow tract (RVOT) VT, extrasystoles, idiopathic left ventricular tachycardia (ILVT), idiopathic propranolol-sensitive VT (IPVT), catecholaminergic polymorphic VT (CPVT), Brugada syndrome, and long QT syndrome (LQTS). RVOT VT, ILVT, and IPVT are referred to as idiopathic VT and generally do not have a familial basis. RVOT VT and ILVT are monomorphic, whereas IPVT may be monomorphic or polymorphic. The idiopathic VTs are classified by the ventricle of origin, the response to pharmacologic agents, catecholamine dependence, and the specific morphologic features of the arrhythmia. CPVT, Brugada syndrome, and LQTS are inherited ion channelopathies. CPVT may present as bidirectional VT, polymorphic VT, or catecholaminergic ventricular fibrillation. Syncope and sudden death in Brugada syndrome are usually due to polymorphic VT. The characteristic arrhythmia of LQTS is torsades de pointes. Overall, patients with idiopathic VT have a better prognosis than do patients with ventricular arrhythmias and structural heart disease. Initial treatment approach is pharmacologic and radiofrequency ablation is curative in most patients. However, radiofrequency ablation is not useful in the management of inherited ion channelopathies. Prognosis for patients with VT secondary to ion channelopathies is variable. High-risk patients (recurrent syncope and sudden cardiac death survivors) with inherited ion channelopathies benefit from implantable cardioverter-defibrillator placement. This paper reviews the mechanism, clinical presentation, and management of VT in the absence of structural heart disease.