Sophie van Malderen

Comparative study of the failure rates among 3 implantable defibrillator leads

BACKGROUND After the introduction of the Biotronik Linox S/SD high-voltage lead, several cases of early failure have been observed. OBJECTIVE The purpose of this article was to assess the performance of the Linox S/SD lead in comparison to 2 other contemporary leads. METHODS We used the prospective Erasmus MC ICD registry to identify all implanted Linox S/SD (n = 408), Durata (St. Jude Medical, model 7122) (n = 340), and Endotak Reliance (Boston Scientific, models 0155, 0138, and 0158) (n = 343) leads. Lead failure was defined by low- or high-voltage impedance, failure to capture, sense or defibrillate, or the presence of nonphysiological signals not due to external interference. RESULTS During a median follow-up of 5.1 years, 24 Linox (5.9%), 5 Endotak (1.5%), and 5 Durata (1.5%) leads failed. At 5-year follow-up, the cumulative failure rate of Linox leads (6.4%) was higher than that of Endotak (0.4%; P < .0001) and Durata (2.0%; P = .003) leads. The incidence rate was higher in Linox leads (1.3 per 100 patient-years) than in Endotak and Durata leads (0.2 and 0.3 per 100 patient-years, respectively; P < .001). A log-log analysis of the cumulative hazard for Linox leads functioning at 3-year follow-up revealed a stable failure rate of 3% per year. The majority of failures consisted of noise (62.5%) and abnormal impedance (33.3%). CONCLUSION This study demonstrates a higher failure rate of Linox S/SD high-voltage leads compared to contemporary leads. Although the mechanism of lead failure is unclear, the majority presents with abnormal electrical parameters. Comprehensive monitoring of Linox S/SD high-voltage leads includes remote monitoring to facilitate early detection of lead failure.

SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies

SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome. On the other hand, mutations in SCN4A encoding the α-subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A-associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy (DMPK gene) and one family had a Thomsen disease myotonia congenita (CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.

Contribution of Cardiac Sodium Channel β-Subunit Variants to Brugada Syndrome

BACKGROUND Brugada syndrome (BrS) is an inheritable cardiac disease associated with syncope, malignant ventricular arrhythmias and sudden cardiac death. The largest proportion of mutations in BrS is found in the SCN5A gene encoding the α-subunit of cardiac sodium channels (Nav1.5). Causal SCN5A mutations are present in 18-30% of BrS patients. The additional genetic diagnostic yield of variants in cardiac sodium channel β-subunits in BrS patients was explored and functional studies on 3 novel candidate variants were performed. METHODSANDRESULTS TheSCN1B-SCN4B genes were screened, which encode the 5 sodium channel β-subunits, in a SCN5A negative BrS population (n=74). Five novel variants were detected; in silico pathogenicity prediction classified 4 variants as possibly disease causing. Three variants were selected for functional study. These variants caused only limited alterations of Nav1.5 function. Next generation sequencing of a panel of 88 arrhythmia genes could not identify other major causal mutations. CONCLUSIONS It was hypothesized that the studied variants are not the primary cause of BrS in these patients. However, because small functional effects of these β-subunit variants can be discriminated, they might contribute to the BrS phenotype and be considered a risk factor. The existence of these risk factors can give an explanation to the reduced penetrance and variable expressivity seen in this syndrome. We therefore recommend including the SCN1-4B genes in a next generation sequencing-based gene panel.

‘Born’ with a ‘dead’-end-tract resulting in arrhythmias in the aorto-mitral continuity: coincidence, causation, and ‘commensuration’

Ventricular arrhythmias originating from the aortomitral continuity: an uncommon variant of left ventricular outflow tract tachycardia by J. Chen et al. , on page 388 The word coincidence is derived from the Latin cum- (‘with’, ‘together’) and incidere (a verb composed from ‘ in ’ and ‘ cadere ’: ‘to fall on’, ‘to happen’). As such, a coincidence occurs when something uncanny, accidental, and unexpected happens under conditions named, but not under a defined relationship. On the other hand, causation (also referred to as causality) is the relationship between an event (the cause) and a second event (the effect), where the second event is understood as a consequence of the first one. One of the most challenging types of research in biology is to determine the causation between observed phenomena. In order to prove causation, sophisticated animal or in vitro experiments are often required. However, invariably the first step is an observation which draws attention to an unexpected phenomenon occurring simultaneously in patients. In this issue of the Journal, Chen et al .1present their experience with ventricular and supraventricular arrhythmias originating from the region called aorto-mitral continuity (AMC). The primary aim of the manuscript was to describe the electrocardiographic (ECG) characteristics of premature ventricular complexes (PVCs) originating from this region. The ECG characteristics of AMC-related ventricular tachycardia (VT) are very similar to those of other left ventricular outflow tract tachycardias and they may even overlap because they all …

Prolonged right ventricular ejection delay identifies high risk patients and gender differences in Brugada syndrome.

BACKGROUND AND OBJECTIVES Right ventricular (RV) conduction delay has been suggested as an underlying pathophysiological mechanism in Brugada syndrome (BS). In this cross-sectional study we non-invasively assessed the value of echocardiographic markers reflecting ventricular ejection delay to further assess electromechanical abnormalities in BS and to identify patients at risk for life-threatening arrhythmic events. Furthermore, we sought to assess differences in ejection delays between genders because male BS patients demonstrate a more malignant clinical phenotype. METHODS 124 BS patients (57.3% males) and 62 controls (CTR) (48.4% males) were included. Using Tissue Velocity Imaging, the ejection delay, determined as the time from QRS onset to the onset of the sustained systolic contraction, was measured for both RV free wall (RVED) and lateral LV wall (LVED). From these parameters, the interventricular ejection delay between both walls (IVED) was calculated. RESULTS BS patients had longer RVEDs and IVEDs compared to the CTR. BS patients with a previous history of syncope or spontaneous ventricular arrhythmia showed the longest RVEDs and IVEDs. Male BS patients demonstrated longer RVEDs and IVEDs than females. Male BS patients with malignant events had the longest delays. No significant differences regarding LVED were observed between BS patients and CTR. CONCLUSIONS We demonstrated that a previous history of malignant events was associated with longer RVEDs. Our findings supported the RV conduction delay mechanism behind BS and demonstrated for the first time that the predominant malignant male Brugada phenotype might also be the result of a more delayed RV conduction in males.

Mismatch between the origin of premature ventricular complexes and the noncompacted myocardium in patients with noncompaction cardiomyopathy patients: involvement of the conduction system?

Noncompaction cardiomyopathy (NCCM) is considered to be the result of an arrest in the normal myocardial embryogenesis. The histological, developmental, and electrophysiological explanation of ventricular arrhythmias in NCCM is still unknown. The aim of this study was to determine the origin of premature ventricular contractions (PVCs) in NCCM and to identify any predominant arrhythmic foci.

Paradoxical embolism in a patient with a large tricuspid myxoma and patent foramen ovale

A 61-year-old man with an uneventful medical history presented with two transient ischaemic attacks (TIA) with bulbar and peripheral deficit. Transthoracal and transoesophageal echocardiography revealed a patent foramen ovale (PFO) and a large, lobulated, pedunculated, non-calcified, and heterogenic mass attached to the septal tricuspid leaflet ( Panels 1–3 ) with important mobility. MRI suggested a myxoma, being isointense on T1-weighted turbo spin echo (TSE), iso-hyperintense on T2-weighted TSE, and hypointense on spoiled gradient echo. First-pass perfusion showed a heterogeneous and hypoperfused enhancement pattern, while contrast-enhanced inversion recovery images showed diffuse hyperenhancement ( Panels 4 and 5 ). Carotid echo-Doppler, Holter monitoring, and a …

What the internist should know about hereditary muscle channelopathies

Abstract Objectives: Non-dystrophic myotonia, periodic paralysis and, to a certain extent, myotonic dystrophies are rare hereditary skeletal muscle channelopathies, charactarized by myotonia or episodic muscle weakness. This review highlights the diagnostic challenges and treatment options. Results: Some of these rare skeletal muscle disorders are associated with a broad range of systemic and nonspecific muscle symptoms. Consequently, patients are often referred to the internist before seeing a neurologist. This article provides clinical clues to better diagnose an tackle these unique disorders. Conclusion: A increased knowledge will reduce the diagnostic delay, improve monitoring and treatment, and might even prevent potentially life-threatening conditions as seen in DM.