Julia Cadrin-Tourigny

Severe left ventricular dysfunction in infants with ventricular preexcitation

e t ntroduction he role of dyssynchrony in the pathogenesis of heart failre has been the subject of numerous studies on cardiac esynchronization therapy. Detrimental cardiac remodeling as been described in the setting of isolated left bundle ranch block or its induction by right ventricular apical acing, further underpinning the impact of dyssynchrony in he cascade of heart failure. More recently, a few reports ave emerged linking accessory pathway–mediated ventriclar preexcitation with left ventricular dyssynchrony and ysfunction. In this report, we extend this observation to nfants younger than 6 months with severe left ventricular ysfunction associated with preexcitation in the absence of ocumented supraventricular tachycardia.

Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) is an uncommon but increasingly recognized inherited cardiomyopathy that is associated with malignant ventricular arrhythmias and sudden cardiac death, particularly in young individuals. The implantable cardioverter-defibrillator (ICD) is widely regarded as the only treatment modality with evidence to support improved survival in patients with ARVC and secondary prevention indications. In contrast, there is no universally accepted risk stratification scheme to guide ICD therapy for primary prevention against sudden cardiac death. Potential benefits must be weighed against the considerable risks of complications and inappropriate shocks in this young patient population. This article tackles the challenges of risk stratification for sudden cardiac death in ARVC and critically appraises available evidence for various proposed risk factors. The authors’ over-arching objective is to provide the clinician with evidence-based guidance to inform decisions regarding the selection of appropriate candidates with ARVC for ICD therapy.

Systolic blood pressure and mortality in patients with atrial fibrillation and heart failure: insights from the AFFIRM and AF-CHF studies

To investigate the association between baseline systolic blood pressure levels and mortality in patients with AF with or without LV dysfunction. Hypertension leads to cardiovascular disease but, in specific groups, low blood pressure has been associated with a paradoxical increase in mortality. In patients with AF and heart failure, the relationship between blood pressure and death remains largely unknown.

Loss-of-Function KCNE2 Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

Background— Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2-encoded voltage-gated channel &bgr;-subunit, is limited. We sought to further characterize its clinical phenotype. Methods and Results— Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database. Clinical features were assessed, while reported KCNE2 mutations were evaluated for genotype–phenotype segregation and classified according to the contemporary American College of Medical Genetics guidelines. Twenty-seven probands possessed reported pathogenic KCNE2 mutations, while a MEDLINE search identified 17 additional LQT6 cases providing clinical and genetic data. Sixteen probands had normal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to QT-prolonging stressors, 10 had other LQTS pathogenic mutations, and 10 did not have an LQTS phenotype. Although the remaining 8 subjects had an LQTS phenotype, evidence suggested that the KCNE2 variant was not the underlying culprit. The collective frequency of KCNE2 variants implicated in LQT6 in the Exome Aggregation Consortium database was 1.4%, in comparison with a 0.0005% estimated clinical prevalence for LQT6. Conclusions— On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype–phenotype segregation, our findings suggest that many KCNE2 variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, KCNE2 variants may confer proarrhythmic susceptibility when provoked by additional environmental/acquired or genetic factors, or both.

Pharmacotherapy for inherited arrhythmia syndromes: mechanistic basis, clinical trial evidence and practical application.

In the absence of structural heart disease, sudden cardiac death is frequently caused by inherited arrhythmia syndromes, such as long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. Managing these conditions often requires a combination of lifestyle modification, pharmacotherapy and less frequently, invasive therapy. Over the past decade, patient management has been greatly enhanced by tailored pharmacotherapy as a result of a deeper appreciation for arrhythmia mechanisms and supportive evidence from multicenter cohort studies. This article reviews current knowledge regarding drug therapy for inherited arrhythmias. Anti-arrhythmic mechanisms and available clinical evidence are highlighted while maintaining a practical perspective on patient management.

Atrial fibrillation in young patients

ABSTRACT Introduction: Atrial fibrillation (AF) is the most frequent arrhythmia worldwide. While mostly seen in elderly, it can also affect young adults (≤ 45 years of age), older adolescent, and children. Areas covered: The aim of this review is to provide an overview of the current management of AF in young patients. Specific issues arise over diagnostic workup as well as antiarrhythmic and anticoagulation therapies. The future management and diagnostic strategies are also discussed. Expert commentary: Management of AF in the young adult is largely extrapolated from adult studies and guidelines. In this population, AF could reveal a genetic pathology (e.g. Brugada, Long QT or Short QT syndromes) or be the initial presentation of a cardiomyopathy. Therefore, thorough workup in the young population to eliminate potential malignant pathology

Reply : Observational Versus Randomized: Sliding Toward Nonevidence-Based Medicine

We thank Dr. Kotecha and colleagues for their interest in our study [(1)][1]. However, we feel obliged to correct several inaccurate and misleading statements, including the catchy but deceptive title. Although Dr. Kotecha and colleagues portrayed their pooled analysis [(2)][2] as above the fray of

Amiodarone and Beta-Blockers in Patients With Heart Failure and Atrial Fibrillation

We appreciate the editorial by Piccini and Allen [(1)][1], which critically appraises the evidence for and against a survival benefit associated with β-blockers in patients with heart failure with reduced ejection fraction and concomitant atrial fibrillation. The balanced analysis highlights the

Hereditary Cardiac Conduction Diseases

Cardiac conduction diseases (CCD) are a group of electrical defects of the heart with multiple hereditary and non-hereditary etiologies. The clinical spectrum of CCD includes asymptomatic patients with incidental electrocardiographic abnormalities, as well as patients presenting with syncope and cardiac arrest. CCD can be associated with other hereditary syndromes including Brugada syndrome, cardiomyopathy and neuromuscular diseases. A comprehensive clinical evaluation of patients with CCD including a detailed family history as well as molecular diagnostics in select cases are key to establishing the correct etiology, guiding patient management and directing family screening. In this chapter, we discuss the differential diagnosis of CCD, guiding principles in cardiogenetic evaluation as well as specific genotype-phenotype correlations.

BLOOD PRESSURE AND ATRIAL FIBRILLATION: A COMBINED ATRIAL FIBRILLATION-CONGESTIVE HEART FAILURE AND ATRIAL FIBRILLATION FOLLOW-UP INVESTIGATION OF RHYTHM MANAGEMENT ANALYSIS

Although hypertension is an established risk factor for atrial fibrillation (AF), the relationship between systolic blood pressure (SBP), recurrent AF, and AF burden is less well understood. Moreover, the interplay between SBP and AF may differ in patients with and without left ventricular