High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Background: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene.

Methods And Results: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry.

Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2.

Objective: We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population.

Cardiac amyloidosis: updates in diagnosis and management.

Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease.

Long-term follow-up on high-rate cut-off programming for implantable cardioverter defibrillators in primary prevention patients with left ventricular systolic dysfunction.

Aims: Implantable cardioverter defibrillators (ICDs) are efficient in reducing mortality in patients with left ventricular systolic dysfunction. High-rate cut-off programming may be effective in reducing appropriate and inappropriate therapies, but as the long-term consequences on morbidity and mortality remain unclear, it is underutilized.

Methods And Results: We prospectively studied 365 consecutive patients (mean age 60 ± 10 years), with ischaemic (63%) or non-ischaemic cardiomyopathy and left ventricular dysfunction (mean ejection fraction 25 ± 7%), who were implanted with an ICD in primary prevention of sudden cardiac death (41% single chamber, 31% dual chamber, and 28% biventricular).

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

Aims: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping.

Methods And Results: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C.

A young patient with Danon disease receives two ICD shocks: why?

We report the case of an 18-year-old man with Danon disease, a genetic disorder inclunding a severe hypertrophic cardiomyopathy with very broad QRS, who had an implantable cardioverter defibrillator for primary prevention. Nine months after implantation, he received two inappropriate shocks due to R-wave double counting during sinus tachycardia. We discuss how to avoid such inappropriate therapy.

Localized constrictive pericarditis after Gore-Tex pericardial substitution.

A 65-year-old patient presented with recurrent cardiac decompensation 12 years after aortic prosthesis replacement and expanded polytetrafluoroethylene (ePTFE) membrane pericardial substitution. Diagnosis of pericardial constriction was difficult. Only one cardiac imaging method, radionuclide ventriculography, was helpful.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.

Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein.

Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV.

Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure.

In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007.

Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21.

Congenital heart defects (CHD) are common in Down syndrome (DS, trisomy 21). Recently, cardiac sympathetic-parasympathetic imbalance has also been documented in DS adults free of any CHD. The KCNJ6 gene located on human chromosome 21 encodes for the Kir3.

Association between plasma LDL particle size, valvular accumulation of oxidized LDL, and inflammation in patients with aortic stenosis.

Objective: In patients with severe aortic stenosis (AS), we examine the association between: (1) the content of oxidized LDL (oxLDL) in the aortic valve and the degree of inflammation and remodeling; (2) The proportion of small dense LDL particles in the plasma and the presence of oxLDL in the valve along with hemodynamic progression of valve stenosis.

Methods And Results: We have examined 102 explanted AS valves. Tissue remodeling, inflammation, and accumulation of oxLDL were determined.

Roles of PKA, PI3K, and cPLA2 in the NO-mediated negative inotropic effect of beta2-adrenoceptor agonists in guinea pig right papillary muscles.

Although beta(2)-adrenoceptors represent 15-25% of beta-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of beta(2)-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, -5% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 microM) due to activation of beta(1)-adrenoceptors.

Tachycardiomyopathy secondary to nonreentrant atrioventricular nodal tachycardia: recovery after slow pathway ablation.

Nonreentrant atrioventricular (AV) nodal tachycardia is a rare form of arrhythmia due to simultaneous anterograde conduction in dual AV pathways, one atrial impulse triggering two ventricular complexes. We report the case of a 74-year-old man referred for incessant palpitations resistant to antiarrhythmic medication, and effort dyspnea. A nonreentrant AV nodal tachycardia is diagnosed with electrophysiological study.

Abnormal nocturnal heart rate variability and QT dynamics in patients with Brugada syndrome.

Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system.

Methods: In 46 patients (mean age = 41 +/- 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients.

Contractile and relaxant properties of rat-isolated pulmonary veins related to localization and histology.

The aim of this study was to investigate the in vitro vasomotor properties of rat extra-and intralobar pulmonary veins (PVs) related to their localization and to assess the modulatory role of endothelium on these properties. Segments from PVs were mounted in small vessel myograph and stretched at various diameters (D(10), D(20), D(30)) corresponding to intraluminal pressures of 10, 20 or 30 mmHg. At D(10) or D(20), contractile responses to phenylephrine, U46619 and angiotensin II of distal intralobar part of PVs were smaller compared with those of proximal extralobar part, but no longer different when distal part was stretched at D(30).

Conformational state of human cardiac 5-HT(4(g)) receptors influences the functional effects of polyclonal anti-5-HT(4) receptor antibodies.

The functional effects of the anti-G21V antibody directed against the second extracellular loop of human heart 5-HT(4) receptors can differ when the receptors are expressed in different cell lines. Here, we extend these studies to show variation in the responses of 5-HT(4(g)) receptors to the antibody within the same expression system. In a previous report no effect of the anti-G21V antibodies had been shown upon 5-HT(4(g)) receptors expressed in CHO cells.

Different criteria of cardiac resynchronization therapy and their prognostic value for worsening heart failure or major arrhythmic events in patients with idiopathic dilated cardiomyopathy.

There are still controversies about pertinent criteria for cardiac resynchronization therapy (CRT) and prophylactic indications for biventricular cardioverter-defibrillators, particularly in idiopathic dilated cardiomyopathy (IDC). This study compared several criteria for resynchronization therapy in IDC among those of several completed trials. In 201 patients with IDC, the relative risk for (1) death from heart failure (HF) or heart transplantation and (2) sudden death or sustained ventricular tachyarrhythmia were calculated separately according to the inclusion criteria of the Multisite Stimulation in Cardiomyopathy (MUSTIC), InSync, Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Pacing Therapies for Congestive Heart Failure (PATH-CHF), Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), and CONTAK studies.

High efficiency activation of L-type Ca2+ current by 5-HT in human atrial myocytes.

In human atrial myocytes, serotonin rather than sympathetic, stimulation is more frequently associated with atrial fibrillation. So does the arrhythmogenic effect of serotonin result from the mechanism of action of the receptor or the context of its action upon cardiac myocytes? The capacity of agonists to produce cAMP followed the sequence 5-HT < Iso < Forskolin to increase ICaL with 5-HT = Iso = Forskolin. The simultaneous application of threshold concentrations of 5-HT and Iso maximally increased ICaL.

QT dispersion in nonischemic dilated cardiomyopathy. A long-term evaluation.

Background: In idiopathic dilated cardiomyopathy (IDC), the predictive value of QT dispersion is still under debate.

Aims: This study assessed the role of QT dispersion for the long-term risk of cardiac death and of major arrhythmic events in IDC.

Methods And Results: In 162 patients with IDC (age 52+/-12 years), the QT interval on a 12-lead ECG was measured manually.